Publications by authors named "Yibin Feng"

143 Publications

Immunomodulatory potential of natural products from herbal medicines as immune checkpoints inhibitors: Helping to fight against cancer via multiple targets.

Med Res Rev 2022 Jan 14. Epub 2022 Jan 14.

School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.

Immunotherapy sheds new light to cancer treatment and is satisfied by cancer patients. However, immunotoxicity, single-source antibodies, and single-targeting stratege are potential challenges to the success of cancer immunotherapy. A huge number of promising lead compounds for cancer treatment are of natural origin from herbal medicines. The application of natural products from herbal medicines that have immunomodulatory properties could alter the landscape of immunotherapy drastically. The present study summarizes current medication for cancer immunotherapy and discusses the potential chemicals from herbal medicines as immune checkpoint inhibitors that have a broad range of immunomodulatory effects. Therefore, this review provides valuable insights into the efficacy and mechanism of actions of cancer immunotherapies, including natural products and combined treatment with immune checkpoint inhibitors, which could confer an improved clinical outcome for cancer treatment.
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http://dx.doi.org/10.1002/med.21876DOI Listing
January 2022

Epigenetic regulation of ferroptosis via ETS1/miR-23a-3p/ACSL4 axis mediates sorafenib resistance in human hepatocellular carcinoma.

J Exp Clin Cancer Res 2022 Jan 3;41(1). Epub 2022 Jan 3.

School of Chinese Medicine, The University of Hong Kong, Hong Kong, China.

Background: Drug resistance to sorafenib greatly limited the benefits of treatment in patients with hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate in the development of drug resistance. The key miRNA regulators related to the clinical outcome of sorafenib treatment and their molecular mechanisms remain to be identified.

Methods: The clinical significance of miRNA-related epigenetic changes in sorafenib-resistant HCC was evaluated by analyzing publicly available databases and in-house human HCC tissues. The biological functions of miR-23a-3p were investigated both in vitro and in vivo. Proteomics and bioinformatics analyses were conducted to identify the mechanisms that regulating miR-23a-3p. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were used to validate the binding relationship of miR-23a-3p and its targets.

Results: We found that miR-23a-3p was the most prominent miRNA in HCC, which was overexpressed in sorafenib non-responders and indicated poor survival and HCC relapse. Sorafenib-resistant cells exhibited increased miR-23a-3p transcription in an ETS Proto-Oncogene 1 (ETS1)-dependent manner. CRISPR-Cas9 knockout of miR-23a-3p improved sorafenib response in HCC cells as well as orthotopic HCC tumours. Proteomics analysis suggested that sorafenib-induced ferroptosis was the key pathway suppressed by miR-23a-3p with reduced cellular iron accumulation and lipid peroxidation. MiR-23a-3p directly targeted the 3'-untranslated regions (UTR) of ACSL4, the key positive regulator of ferroptosis. The miR-23a-3p inhibitor rescued ACSL4 expression and induced ferrotoptic cell death in sorafenib-treated HCC cells. The co-delivery of ACSL4 siRNA and miR-23a-3p inhibitor abolished sorafenib response.

Conclusion: Our study demonstrates that ETS1/miR-23a-3p/ACSL4 axis contributes to sorafenib resistance in HCC through regulating ferroptosis. Our findings suggest that miR-23a-3p could be a potential target to improve sorafenib responsiveness in HCC patients.
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http://dx.doi.org/10.1186/s13046-021-02208-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722264PMC
January 2022

Adjunctive berberine reduces antipsychotic-associated weight gain and metabolic syndrome in patients with schizophrenia: a randomized controlled trial.

Psychiatry Clin Neurosci 2021 Dec 21. Epub 2021 Dec 21.

LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Aim: The aim of this study was to evaluate the efficacy and safety of berberine as an adjuvant in treating antipsychotic-associated weight gain and metabolic syndrome.

Methods: One hundred thirteen participants with schizophrenia spectrum disorders who had developed metabolic syndrome were recruited. They were randomly assigned to berberine (600 mg/d, n = 58) or placebo (n = 55) groups for 12 weeks. The primary outcome was the change from baseline to week 12 in net weight. Secondary outcomes included body mass index, waist circumference, serum glucose and lipid profiles, and the severity of psychotic symptoms.

Results: Compared with the placebo group, the berberine group showed a significantly greater reduction in weight gain at 9 weeks (mean difference [MD], -0.75; 95% CI, -1.42 to -0.07 [P = 0.031, d = 0.41]) and 12 weeks (MD, -1.08; 95% CI, -1.76 to -0.40 [P = 0.002, d = 0.59]). Patients who received berberine also showed statistically significant improvements in end point in body mass index (MD, -0.41; 95% CI, -0.65 to -0.17 [P = 0.001, d = 0.64]), total cholesterol (MD, -0.58; 95% CI, -0.74 to -0.41 [P < 0.001, d = 1.31]), low-density lipoprotein (MD, -0.52; 95% CI, -0.68 to -0.35 [P < 0.001, d = 1.19]), and glycated hemoglobin (MD, -0.09; 95% CI, -0.18 to 0 [P = 0.05, d = 0.37]). Berberine was well tolerated without serious adverse events and aggravation of psychotic symptoms compared with placebo.

Conclusion: The findings suggest that berberine is effective in attenuating antipsychotic-associated weight gain and metabolic syndrome.
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http://dx.doi.org/10.1111/pcn.13323DOI Listing
December 2021

Chinese Medicine for Coronavirus Disease 2019 (COVID-19): A GRADE-Assessed Systematic Review and Meta-Analysis.

Am J Chin Med 2021 Dec 2:1-31. Epub 2021 Dec 2.

School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong SAR, P. R. China.

Coronavirus disease 2019 (COVID-19) has caused enormous public health and socioeconomic burden globally. This study aims to evaluate the efficacy and safety of Chinese medicine (CM) against COVID-19. Eleven databases were searched on April 30, 2021, and 52 studies were included. The RoB 2.0, ROBINS-I, and GRADE tools were employed to assess the risks and evidence grades. The findings with moderate certainty in GRADE showed that compared with routine treatment (RT), Lianhua Qingwen granules (LHQW) adjunctive to RT showed significantly improved efficacy rate (relative risk (RR) = 1.19, 95% confidence interval (CI): [1.09, 1.31]), febrile score (standard mean difference (SMD) = -1.21, 95% CI: [-1.43, -0.99]), and computerized tomography (CT) lung images (RR = 1.23, 95% CI: [1.10, 1.38]); Qingfei Paidu decoction (QFPD) plus RT significantly shortened the length of hospital stay (SMD = -1.83, 95% CI: [-2.18, -1.48]); Feiyan Yihao formula (FYYH) plus RT significantly improved the clinical efficacy rate (RR = 1.07, 95% CI: [1, 1.15]), febrile time (SMD = -0.02, 95% CI: [-0.23, 0.19]), and time to negative PCR test for COVID-19 (SMD = -0.72, 95% CI: [-0.94, -0.51]). Adjunctive effects of CM with lower certainty of evidence were found, including the improvements of symptoms, laboratory findings, and mortality. No or mild adverse events were observed in most of the studies. In conclusion, the current evidence indicates that CM formulae, particularly LHQW, QFPD, and FYYH, have adjunctive effects on the standard treatment of COVID-19.
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http://dx.doi.org/10.1142/S0192415X2250001XDOI Listing
December 2021

Gallic Acid and Diabetes Mellitus: Its Association with Oxidative Stress.

Molecules 2021 Nov 24;26(23). Epub 2021 Nov 24.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Diabetes mellitus (DM) is a severe chronic metabolic disease with increased mortality and morbidity. The pathological progression of DM is intimately connected with the formation and activation of oxidative stress (OS). Especially, the involvement of OS with hyperglycemia, insulin resistance, and inflammation has shown a vital role in the pathophysiological development of DM and related complications. Interestingly, accumulating studies have focused on the exploration of natural antioxidants for their improvement on DM. Of specific interest is gallic acid (GA), which is rich in many edible and herbal plants and has progressively demonstrated robust antioxidative and anti-inflammatory effects on metabolic disorders. To provide a better understanding of its potential therapeutic impacts and enhancement of human health care, the available research evidence supporting the effective antidiabetic properties of GA and relevant derivatives are needed to be summarized and discussed, with emphasis on its regulation on OS and inflammation against DM. This review aims to highlight the latest viewpoints and current research information on the role of OS in diabetes and to provide scientific support for GA as a potential antihypoglycemic agent for DM and its complications.
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http://dx.doi.org/10.3390/molecules26237115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658971PMC
November 2021

Transcriptional Profiling and Machine Learning Unveil a Concordant Biosignature of Type I Interferon-Inducible Host Response Across Nasal Swab and Pulmonary Tissue for COVID-19 Diagnosis.

Front Immunol 2021 22;12:733171. Epub 2021 Nov 22.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.

Background: COVID-19, caused by SARS-CoV-2 virus, is a global pandemic with high mortality and morbidity. Limited diagnostic methods hampered the infection control. Since the direct detection of virus mainly by RT-PCR may cause false-negative outcome, host response-dependent testing may serve as a complementary approach for improving COVID-19 diagnosis.

Objective: Our study discovered a highly-preserved transcriptional profile of Type I interferon (IFN-I)-dependent genes for COVID-19 complementary diagnosis.

Methods: Computational language R-dependent machine learning was adopted for mining highly-conserved transcriptional profile (RNA-sequencing) across heterogeneous samples infected by SARS-CoV-2 and other respiratory infections. The transcriptomics/high-throughput sequencing data were retrieved from NCBI-GEO datasets (GSE32155, GSE147507, GSE150316, GSE162835, GSE163151, GSE171668, GSE182569). Mathematical approaches for homological analysis were as follows: adjusted rand index-related similarity analysis, geometric and multi-dimensional data interpretation, UpsetR, t-distributed Stochastic Neighbor Embedding (t-SNE), and Weighted Gene Co-expression Network Analysis (WGCNA). Besides, Interferome Database was used for predicting the transcriptional factors possessing IFN-I promoter-binding sites to the key IFN-I genes for COVID-19 diagnosis.

Results: In this study, we identified a highly-preserved gene module between SARS-CoV-2 infected nasal swab and postmortem lung tissue regulating IFN-I signaling for COVID-19 complementary diagnosis, in which the following 14 IFN-I-stimulated genes are highly-conserved, including BST2, IFIT1, IFIT2, IFIT3, IFITM1, ISG15, MX1, MX2, OAS1, OAS2, OAS3, OASL, RSAD2, and STAT1. The stratified severity of COVID-19 may also be identified by the transcriptional level of these 14 IFN-I genes.

Conclusion: Using transcriptional and computational analysis on RNA-seq data retrieved from NCBI-GEO, we identified a highly-preserved 14-gene transcriptional profile regulating IFN-I signaling in nasal swab and postmortem lung tissue infected by SARS-CoV-2. Such a conserved biosignature involved in IFN-I-related host response may be leveraged for COVID-19 diagnosis.
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http://dx.doi.org/10.3389/fimmu.2021.733171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647662PMC
January 2022

Highly Efficient Magnetic Propulsion of NiFe Nanorod-Based Miniature Swimmers in Three Dimensions.

ACS Appl Mater Interfaces 2021 Dec 1;13(49):58898-58907. Epub 2021 Dec 1.

Hubei Engineering Research Center of Weak Magnetic-field Detection & College of Science, China Three Gorges University, Yichang, Hubei 443002, China.

Magnetically actuated miniature robots have attracted the attention of the scientific community over the past two decades, but the confined workspace of their manipulation system (typically a tri-axial coil or eight electromagnetic coils) and the low efficiency of propulsion have limited their utility. Here, we describe a highly efficient NiFe nanorod-based magnetic miniature swimmer that can be manipulated in 3D spaces using two pairs of coils placed in the - horizontal plane. In the new swimmer, the shape symmetry is broken along its body, and the asymmetry in magnetizations is introduced perpendicular to the long axis of its body simultaneously. Such a combined asymmetry design offers favorable controllability in planar magnetic fields, which relaxes the multi-axial coil requirement of the commonly used manipulation system and thus reduces the restriction on the shape and size of the workspaces. The new swimmers display efficient 3D propulsion, with a speed of over 5000 μm s (∼3 body length s) and powerful locomotion in biological media such as raw human blood. The fuel utilization efficiency of the swimmer, defined as the ratio of the distance to the net input work in one period, was estimated to be approximately from 10 to 10 m/J, which is significantly higher than that of magnetic motors with a slender body. Moreover, to provide practical support for further potential use, we demonstrated that the swimmer is able to perform incision operations as a minimally invasive microsurgical tool. Such a swimmer actuation strategy provides a simple and efficient way for 3D manipulation of magnetic miniature robots, offering great potential for future biomedical and other applications.
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http://dx.doi.org/10.1021/acsami.1c16677DOI Listing
December 2021

Berberine suppresses advanced glycation end products-associated diabetic retinopathy in hyperglycemic mice.

Clin Transl Med 2021 11;11(11):e569

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.

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http://dx.doi.org/10.1002/ctm2.569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567055PMC
November 2021

The Role of Protein SUMOylation in Human Hepatocellular Carcinoma: A Potential Target of New Drug Discovery and Development.

Cancers (Basel) 2021 Nov 14;13(22). Epub 2021 Nov 14.

School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China.

Small ubiquitin-like modifier (SUMO) is a highly conserved post-translational modification protein, mainly found in eukaryotes. They are widely expressed in different tissues, including the liver. As an essential post-translational modification, SUMOylation is involved in many necessary regulations in cells. It plays a vital role in DNA repair, transcription regulation, protein stability and cell cycle progression. Increasing shreds of evidence show that SUMOylation is closely related to Hepatocellular carcinoma (HCC). The high expression of SUMOs in the inflammatory hepatic tissue may lead to the carcinogenesis of HCC. At the same time, SUMOs will upregulate the proliferation and survival of HCC, migration, invasion and metastasis of HCC, tumour microenvironment as well as drug resistance. This study reviewed the role of SUMOylation in liver cancer. In addition, it also discussed natural compounds that modulate SUMO and target SUMO drugs in clinical trials. Considering the critical role of SUMO protein in the occurrence of HCC, the drug regulation of SUMOylation may become a potential target for treatment, prognostic monitoring and adjuvant chemotherapy of HCC.
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http://dx.doi.org/10.3390/cancers13225700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616375PMC
November 2021

Berberine improves insulin-induced diabetic retinopathy through exclusively suppressing Akt/mTOR-mediated HIF-1α/VEGF activation in retina endothelial cells.

Int J Biol Sci 2021 20;17(15):4316-4326. Epub 2021 Oct 20.

School of Chinese Medicine, The University of Hong Kong.

Insulin therapy is the major treatment of glycaemic control in type I diabetes mellitus (DM) and advanced type II DM patients who fail to respond to oral hypoglycemic agents. Nonetheless, insulin therapy is deemed unsuccessful in controlling the incidence of diabetic retinopathy (DR) and is likely a risk factor. Berberine, an isoquinoline alkaloid, has caught great attention towards its anti-diabetic mechanisms. This study aims to investigate the effect of berberine in decelerating DR progression in insulin-treated DM. To better understand the therapeutic potential of berberine in the presence of insulin, we elaborated the action of mechanism whether berberine inhibited retinal expression of HIF-1α and VEGF through regulating AKT/mTOR pathway. Suppression of insulin-induced neovasculature of retina endothelial cells by berberine was also studied. Lastly, the efficacy and safety of berberine as adjuvant therapy for the treatment of DR were systemically investigated in experimental type I and type II DM mice with insulin treatment. Among various types of retinal cells, the activity of HIF-1α and VEGF in retinal endothelial cells could be particularly and exclusively stimulated by insulin intervention, which could be inhibited by berberine treatment in a dose- and time-dependent manner. Berberine suppressed Akt/mTOR activity in these cells, and restoration of Akt/mTOR signalling attenuated berberine's inhibition on HIF-1α and VEGF expression. Berberine suppressed the progression of DR in experimental type I and type II diabetic mice receiving insulin therapy. Berberine improves insulin-induced diabetic retinopathy in type I and II diabetes through inhibiting insulin-induced activation of retinal endotheliocytes via Akt/mTOR/ HIF-1α/VEGF pathway.
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http://dx.doi.org/10.7150/ijbs.62868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579442PMC
December 2021

Systematic Review with Meta-Analysis: Effectiveness and Safety of Acupuncture as Adjuvant Therapy for Side Effects Management in Drug Therapy-Receiving Breast Cancer Patients.

Evid Based Complement Alternat Med 2021 12;2021:9949777. Epub 2021 Oct 12.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Objective: To investigate the potential benefits and safety of acupuncture on managing side effects induced by drug therapies in patients with breast cancer using a PRISMA standard systematic review and meta-analysis.

Methods: Published randomised controlled trials from nine databases in English and Chinese language were searched. Trials with a real acupuncture treatment group and a control group with sham acupuncture, no treatment, or waitlist control were included. The primary outcome of this study was the therapeutic effects on five symptoms induced by drug therapies, including gastrointestinal disorder, neuropathy, arthralgia, joint symptoms, and cognitive impairment. The quality of life was assessed as a secondary outcome. The risk of bias of each study was analysed according to the Cochrane Handbook.

Results: Sixteen randomised controlled trials with 1189 participants were included in the meta-analysis. The primary outcome and all subgroup analyses showed statistically significant improvements in the management of side effects by real acupuncture. The quality of life of patients has enhanced during the treatment.

Conclusion: Although the number of publications is limited, a clear preliminary conclusion could be drawn by the meta-analysis, suggesting the beneficial adjuvant role of acupuncture in patients with breast cancer who receive drug therapies. No serious adverse events were observed from all the RCTs, and the safety of acupuncture is ascertained. More standardised and sophisticated large-scale randomised controlled trials are needed to evaluate the findings further.
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http://dx.doi.org/10.1155/2021/9949777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526206PMC
October 2021

Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management.

Acta Pharm Sin B 2021 Sep 2;11(9):2749-2767. Epub 2021 Feb 2.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR 999077, China.

Diabetic nephropathy (DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease, which causes serious health problems and great financial burden to human society worldwide. Conventional strategies, such as renin-angiotensin-aldosterone system blockade, blood glucose level control, and bodyweight reduction, may not achieve satisfactory outcomes in many clinical practices for DN management. Notably, due to the multi-target function, Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment. Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines. Signaling pathways involved in glucose/lipid metabolism regulation, antioxidation, anti-inflammation, anti-fibrosis, and podocyte protection have been identified as crucial mechanisms of action. Herein, we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials, systematic reviews, and meta-analyses, with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments. We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.
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http://dx.doi.org/10.1016/j.apsb.2020.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463270PMC
September 2021

Efficacy and Safety of Chinese Herbal Medicine on Treatment of Breast Cancer: A Meta-analysis of Randomized Controlled Trials.

Am J Chin Med 2021 16;49(7):1557-1575. Epub 2021 Sep 16.

University of Hong Kong, School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P. R. China.

Breast cancer is currently the most common cancer in women, and it accounts for 11.6% of all cancer diagnoses in 2018. Breast cancer patients frequently resort to alternative medicine in addition to conventional Western therapy. This study is to evaluate clinical effectiveness of Chinese herbal medicine (CHM) on breast cancer by conducting meta-analyses on 81 randomized controlled trials (RCTs) with a total of 7215 subjects from eight databases. All RCTs compared patients using Western therapy alone and those using additional CHM therapy to evaluate the difference of primary (tumor response, mean time to progression (mTTP), overall survival (OS) and progression free survival (PFS)) and secondary outcome measures (tumor markers). Results showed that under the RECIST1.1 criteria, 52% patients with additional CHM therapy (67%, under WHO criteria) achieved either a complete response (CR) or a partial response (PR), compared to 38% patients with Western therapy alone (53%, under the WHO criteria). The risk ratio was 1.31 ([Formula: see text] < 0.00001, 95% CI = 1.15-1.50) for patients with CHM plus Western therapy and 1.25 ([Formula: see text] < 0.00001, 95% CI = 1.18-1.98) for those with Western therapy. Moreover, patients with complementary CHM therapy were associated with an mTTP of 2.79 months longer ([Formula: see text] < 0.00001) and an OS of 1.90 months longer ([Formula: see text] < 0.00001); they also had an increase in 3-year PFS ([Formula: see text]= 0.002), 2- ([Formula: see text]= 0.0002) and 5-year ([Formula: see text]= 0.006) OS rates. Therefore, complementary CHM therapy might demonstrate clinical benefits for breast cancer patients in terms of tumor response and survival. Clinical studies with further stratification of tumor stages and intervention types are highly warranted.
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http://dx.doi.org/10.1142/S0192415X21500737DOI Listing
December 2021

Network Pharmacology-Based Analysis and Experimental Exploration of Antidiabetic Mechanisms of Gegen Qinlian Decoction.

Front Pharmacol 2021 26;12:649606. Epub 2021 Jul 26.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Type-2 diabetes mellitus (T2DM) and therapy options have been studied increasingly due to their rising incidence and prevalence. The trend of applying traditional Chinese medicine (TCM) to treat T2DM is increasing as a crucial medical care for metabolic dysfunctions. Gegen Qinlian decoction (GQL), a well-known classical TCM formula used in China, has been clinically applied to treat various types of chronic metabolic diseases. However, antidiabetic effects of GQL administration during T2DM have never been studied systematically. We assessed physiological and molecular targets associated with therapeutic effects of GQL by evaluating network topological characteristics. The GQL-related biological pathways are closely associated with antidiabetic effects, including the TNF and PI3K-AKT signaling pathways. Associated primary biological processes such as RNA polymerase II promoter transcription participate in the inflammatory response, oxidative stress reduction, and glucose metabolic process, thereby exerting multiple biological effects on the antidiabetic mechanism. Furthermore, our results showed that GQL can affect blood glycemic levels and ameliorate inflammatory symptoms, and liver and pancreas tissue injury in high-fat diet plus streptozotocin-induced diabetic mice. and experiments confirmed that antidiabetic effects of GQL were associated with a modulation of the TNF and PI3K-AKT-MTOR pathways.
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http://dx.doi.org/10.3389/fphar.2021.649606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350346PMC
July 2021

Green Tea and Epigallocatechin Gallate (EGCG) for the Management of Nonalcoholic Fatty Liver Diseases (NAFLD): Insights into the Role of Oxidative Stress and Antioxidant Mechanism.

Antioxidants (Basel) 2021 Jul 5;10(7). Epub 2021 Jul 5.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China.

Nonalcoholic fatty liver diseases (NAFLD) represent a set of liver disorders progressing from steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, which induce huge burden to human health. Many pathophysiological factors are considered to influence NAFLD in a parallel pattern, involving insulin resistance, oxidative stress, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory cascades, fibrogenic reaction, etc. However, the underlying mechanisms, including those that induce NAFLD development, have not been fully understood. Specifically, oxidative stress, mainly mediated by excessive accumulation of reactive oxygen species, has participated in the multiple NAFLD-related signaling by serving as an accelerator. Ameliorating oxidative stress and maintaining redox homeostasis may be a promising approach for the management of NAFLD. Green tea is one of the most important dietary resources of natural antioxidants, above which epigallocatechin gallate (EGCG) notably contributes to its antioxidative action. Accumulative evidence from randomized clinical trials, systematic reviews, and meta-analysis has revealed the beneficial functions of green tea and EGCG in preventing and managing NAFLD, with acceptable safety in the patients. Abundant animal and cellular studies have demonstrated that green tea and EGCG may protect against NAFLD initiation and development by alleviating oxidative stress and the related metabolism dysfunction, inflammation, fibrosis, and tumorigenesis. The targeted signaling pathways may include, but are not limited to, NRF2, AMPK, SIRT1, NF-κB, TLR4/MYD88, TGF-β/SMAD, and PI3K/Akt/FoxO1, etc. In this review, we thoroughly discuss the oxidative stress-related mechanisms involved in NAFLD development, as well as summarize the protective effects and underlying mechanisms of green tea and EGCG against NAFLD.
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http://dx.doi.org/10.3390/antiox10071076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301033PMC
July 2021

The toxicology and detoxification of Aconitum: traditional and modern views.

Chin Med 2021 Jul 27;16(1):61. Epub 2021 Jul 27.

School of Chinese Medicine, The University of Hong Kong, Hong Kong, China.

Aconitum carmichaeli Debx.-derived herbal medicine has been used for anti-inflammation and anti-arrhythmia purpose for more than two thousand years. It is processed into Chuanwu (Radix Aconiti praeparata) and Fuzi (Radix Aconiti lateralis praeparata) in Traditional Chinese Medicine, which are two useful drugs but with toxic properties. There have been patients poisoned by accidental ingestion of Aconitum plants or misuse of the herbal drug, and this is of great concern to study in-depth. In this review, we provided the traditional and contemporary practice of using Aconitum herbs as medicine, from functions, processing methods to toxicity in ethnomedicine aspects to discuss the underlying connections of traditional and modern understanding on the toxicity of Aconitum plants. We summarized the functions and toxicology of the herbal drugs are analyzed from chemical and clinical aspects, with the help of traditional and modern knowledge of medicine. The medicinal doses and lethal doses determined by researches are summarized, and the usage and processing methods are updated and reviewed in the modern view. In addition, clinical management of poisoned cases using western medicine is discussed. This review provides insights and awareness of safety when using Aconitum-derived herbal medicine, and the application of modern scientific knowledge to optimize the detoxification processes. We suggest the possibility to renew the current standard processing method from the official Pharmacopoeia all over the world.
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http://dx.doi.org/10.1186/s13020-021-00472-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314510PMC
July 2021

Facemask Wearing Among Chinese International Students From Hong Kong Studying in United Kingdom Universities During COVID-19: A Mixed Method Study.

Front Psychiatry 2021 16;12:673531. Epub 2021 Jun 16.

School of Public Health, The University of Hong Kong, Hong Kong, China.

The mental health of international students studying abroad has been neglected during the COVID-19 pandemic. This mixed-method study examined perceived public attitudes, personal beliefs, practice and stress toward facemask wearing as a preventive measure against COVID-19 among international University students from Hong Kong studying in the United Kingdom (UK) in the early stage (January-March 2020) of the pandemic. Our study included 2 parts: (i) an exponential, non-discriminative snowball sampling strategy was used to recruit 91 Chinese students studying in the UK to complete an online questionnaire survey, and (ii) online Zoom focus group interviews were conducted with 16 students who completed the online survey to gain an in-depth understanding of their experiences and coping methods during the pandemic. Of the 91 students, 92.3% reported the UK public did not view facemask wearing as a preventive measure. 98.9% believed facemask wearing was an effective preventive measure, but 56% wore facemasks more than half of the time when out in public. 50.5% had internal conflicts of stress both when wearing and not wearing facemasks, which was more common in females than males [(62.5 vs. 31.5%), = 0.004, Relative Risk (RR): 1.99 (1.17, 3.38)]. 61.5% reported public prejudiced attitudes against facemask wearing, also more common in females than males (71.4 vs. 45.7%), = 0.02, RR: 1.56 (1.05, 2.32). The qualitative findings corroborated with the quantitative findings and reported that peer and family support were important for them to face such difficulties, and positive thinking and adaptability were effective methods on stress management. Since the outbreak of COVID-19, Chinese international students have been faced with a difficult, confusing, and sensitive situation. Owing to the ongoing pandemic, rising xenophobia and racist behaviors and the resumption of students' studies studies in the U.K., support from global communities are needed in their pursuit of quality education overseas. Our findings have significant implications on the proactive roles that governments should have, and the need for clear and accurate public health messaging to change public attitudes and mitigate prejudice. Academic institutions and mental health professionals need to proactively provide additional support to Chinese international students.
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http://dx.doi.org/10.3389/fpsyt.2021.673531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242177PMC
June 2021

Functional inhibition of lactate dehydrogenase suppresses pancreatic adenocarcinoma progression.

Clin Transl Med 2021 06;11(6):e467

Li Ka Shing Faculty of Medicine, School of Chinese Medicine, The University of Hong Kong, Hong Kong, China.

Background: Pancreatic adenocarcinoma (PAAD) a highly lethal malignancy. The current use of clinical parameters may not accurately predict the clinical outcome, which further renders the unsatisfactory therapeutic outcome.

Methods: In this study, we retrospectively analyzed the clinical-pathological characteristics and prognosis of 253 PAAD patients. Univariate, multivariate, and Kaplan-Meier survival analyses were conducted to assess risk factors and clinical outcomes. For functional study, we performed bidirectional genetic manipulation of lactate dehydrogenase A (LDHA) in PAAD cell lines to measure PAAD progression by both in vitro and in vivo assays.

Results: LDHA is particularly overexpressed in PAAD tissues and elevated serum LDHA-transcribed isoenzymes-5 (LDH-5) was associated with poorer patients' clinical outcomes. Genetic overexpression of LDHA promoted the proliferation and invasion in vitro, and tumor growth and metastasis in vivo in murine PAAD orthotopic models, while knockdown of LDHA exhibited opposite effects. LDHA-induced L-lactate production was responsible for the LDHA-facilitated PAAD progression. Mechanistically, LDHA overexpression reduced the phosphorylation of metabolic regulator AMPK and promoted the downstream mTOR phosphorylation in PAAD cells. Inhibition of mTOR repressed the LDHA-induced proliferation and invasion. A natural product berberine was selected as functional inhibitor of LDHA, which reduced activity and expression of the protein in PAAD cells. Berberine inhibited PAAD cells proliferation and invasion in vitro, and suppressed tumor progression in vivo. The restoration of LDHA attenuated the suppressive effect of berberine on PAAD.

Conclusions: Our findings suggest that LDHA may be a novel biomarker and potential therapeutic target of human PAAD.
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http://dx.doi.org/10.1002/ctm2.467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238920PMC
June 2021

Edible and Herbal Plants for the Prevention and Management of COVID-19.

Front Pharmacol 2021 28;12:656103. Epub 2021 Apr 28.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

The outbreak of the pandemic coronavirus disease 2019 (COVID-19) has now become a global pandemic spreading throughout the world. Unfortunately, due to the high infectiousness of the novel -coronavirus, it is very likely to become an ordinary epidemic. The development of dietary supplements and functional foods might provide a strategy for the prevention and management of COVID-19. A great diversity of potential edible and medicinal plants and/or natural compounds showed potential benefits in managing SARS, which may also combat COVID-19. Moreover, many plants and compounds have currently been proposed to be protective against COVID-19. This information is based on data-driven approaches and computational chemical biology techniques. In this study, we review promising candidates of edible and medicinal plants for the prevention and management of COVID-19. We primarily focus on analyzing their underlying mechanisms. We aim to identify dietary supplements and functional foods that assist in managing this epidemic. We infer that acetoside, glyasperin, isorhamnetin, and several flavonoid compounds may prevent and/or be effective in managing COVID-19 by targeting the viral infection, reducing the host cytokine storm, regulating the immune response, and providing organ protection. These bioactive dietary components (used either alone or in combination) might assist in the development of dietary supplements or functional foods for managing COVID-19.
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http://dx.doi.org/10.3389/fphar.2021.656103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113769PMC
April 2021

COVID-19 Rehabilitation With Herbal Medicine and Cardiorespiratory Exercise: Protocol for a Clinical Study.

JMIR Res Protoc 2021 May 26;10(5):e25556. Epub 2021 May 26.

Centre for Health and Exercise Science Research, Hong Kong Baptist University, Kowloon, Hong Kong.

Background: Recent studies have revealed that many discharged patients with COVID-19 experience ongoing symptoms months later. Rehabilitation interventions can help address the consequences of COVID-19, including medical, physical, cognitive, and psychological problems. To our knowledge, no studies have investigated the effects of rehabilitation following discharge from hospital for patients with COVID-19.

Objective: The specific aims of this project are to investigate the effects of a 12-week exercise program on pulmonary fibrosis in patients recovering from COVID-19. A further aim will be to examine how Chinese herbal medicines as well as the gut microbiome and its metabolites regulate immune function and possibly autoimmune deficiency in the rehabilitation process.

Methods: In this triple-blinded, randomized, parallel-group, controlled clinical trial, we will recruit adult patients with COVID-19 who have been discharged from hospital in Hong Kong and are experiencing impaired lung function and pulmonary function. A total of 172 eligible patients will be randomized into four equal groups: (1) cardiorespiratory exercise plus Chinese herbal medicines group, (2) cardiorespiratory exercise only group, (3) Chinese herbal medicines only group, and (4) waiting list group (in which participants will receive Chinese herbal medicines after 24 weeks). These treatments will be administered for 12 weeks, with a 12-week follow-up period. Primary outcomes include dyspnea, fatigue, lung function, pulmonary function, blood oxygen levels, immune function, blood coagulation, and related blood biochemistry. Measurements will be recorded prior to initiating the above treatments and repeated at the 13th and 25th weeks of the study. The primary analysis is aimed at comparing the outcomes between groups throughout the study period with an α level of .05 (two-tailed).

Results: The trial has been approved by the university ethics committee following the Declaration of Helsinki (approval number: REC/19-20/0504) in 2020. The trial has been recruiting patients. The data collection will be completed in 24 months, from January 1, 2021, to December 31, 2022.

Conclusions: Given that COVID-19 and its sequelae would persist in human populations, important findings from this study would provide valuable insights into the mechanisms and processes of COVID-19 rehabilitation.

Trial Registration: ClinicalTrials.gov NCT04572360; https://clinicaltrials.gov/ct2/show/NCT04572360.

International Registered Report Identifier (irrid): PRR1-10.2196/25556.
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http://dx.doi.org/10.2196/25556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158531PMC
May 2021

Pharmacokinetics of Anthraquinones from Medicinal Plants.

Front Pharmacol 2021 15;12:638993. Epub 2021 Apr 15.

Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.

Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects. This study aimed to review the pharmacokinetics (PKs) of anthraquinones, which are importantly associated with their pharmacological and toxicological effects. Anthraquinones are absorbed mainly in intestines. The absorption rates of free anthraquinones are faster than those of their conjugated glycosides because of the higher liposolubility. A fluctuation in blood concentration and two absorption peaks of anthraquinones may result from the hepato-intestinal circulation, reabsorption, and transformation. Anthraquinones are widely distributed throughout the body, mainly in blood-flow rich organs and tissues, such as blood, intestines, stomach, liver, lung, kidney, and fat. The metabolic pathways of anthraquinones are hydrolysis, glycuronidation, sulfation, methylation/demethylation, hydroxylation/dehydroxylation, oxidation/reduction (hydrogenation), acetylation and esterification by intestinal flora and liver metabolic enzymes, among which hydrolysis, glycuronidation and sulfation are dominant. Of note, anthraquinones can be transformed into each other. The main excretion routes for anthraquinones are the kidney, recta, and gallbladder. Conclusion: Some anthraquinones and their glycosides, such as aloe-emodin, chrysophanol, emodin, physcion, rhein and sennosides, have attracted the most PK research interest due to their more biological activities and/or detectability. Anthraquinones are mainly absorbed in the intestines and are mostly distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect. Drug-drug interactions influencing PK may provide insights into drug compatibility theory to enhance or reduce pharmacological/toxicological effects in Chinese medicine formulae and deserve deep investigation.
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http://dx.doi.org/10.3389/fphar.2021.638993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082241PMC
April 2021

Efficacy of Herbal Medicines Intervention for Colorectal Cancer Patients With Chemotherapy-Induced Gastrointestinal Toxicity - a Systematic Review and Meta-Analysis.

Front Oncol 2021 25;11:629132. Epub 2021 Mar 25.

Li Ka Shing Faculty of Medicine, School of Chinese Medicine, The University of Hong Kong, Hong Kong, China.

Chemotherapy-induced gastrointestinal (CIGI) toxicity affects the quality of life of patients with colorectal cancer (CRC) and the clinical application of treatment drugs. This review aims to evaluate the efficacy of traditional herbal medicines (HMs) in alleviating symptoms of CIGI toxicity (including nausea and vomiting, anorexia, diarrhea, constipation, oral mucositis, abdominal pain, and abdominal distension), and to explore further individual herb or herbal combinations in alleviating the CIGI toxicity. Nine electronic databases were screened from 2010 to 2020. Twenty-two randomized controlled trials with a total of 1,995 patients evaluating the complementary efficacy of HMs with chemotherapy compared with chemotherapy-alone were included. Further, sensitivity analyses of orally administered multi-ingredient HM interventions were explored based on the composition of HM interventions. The meta-analysis showed that HM treatment combined with chemotherapy significantly alleviated the overall CIGI toxicity (RR = 0.78 [0.72, 0.84], < 0.001, = 44%), nausea and vomiting (RR = 0.74 [0.66, 0.82], < 0.001, = 35%), diarrhea ( = 0.02, RR = 0.64, 95% CI = 0.44-0.93, = 50%), oral mucositis (RR = 0.65 [0.48, 0.88], = 0.005, = 24%), and abdominal distension (RR = 0.36 [0.18, 0.73], = 0.004, = 0%). However, no statistically significant effects of HMs were shown in studies with a double-blind design for CIGI toxicity. Based on the ingredients of the HMs, further sensitivity analyses identified five herbs [ Fisch., Koidz., (Fisch.) Bge., (Franch.) Nannf., and the pericarp of Blanco.] that were associated with significant reductions in CIGI toxicity. A statistically significant effect of HMs combined with chemotherapy on alleviating the overall CIGI toxicity, nausea and vomiting, diarrhea, oral mucositis, or abdominal distension is only shown in studies without a double-blind design. Further well-designed, double-blinded, large-scaled randomized controlled trials (RCTs) are warranted to comprehensively evaluate the treatment efficacy. Further clinical research that includes the five herbs with chemotherapy for patients, the safety of the combinations of these herbs, and the potential synergistic effects of these combinations of herbs should be conducted.
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http://dx.doi.org/10.3389/fonc.2021.629132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044744PMC
March 2021

Gut-liver axis modulation of Panax notoginseng saponins in nonalcoholic fatty liver disease.

Hepatol Int 2021 Apr 3;15(2):350-365. Epub 2021 Mar 3.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 1/F, 10 Sassoon Road, Pokfulam, Hong Kong S.A.R., People's Republic of China.

Background And Aims: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related comorbidity, and it is characterized as a spectrum of liver abnormalities, including inflammation, steatosis, and fibrosis. The gut-liver axis is implicated in the pathogenesis and development of NAFLD. A promising drug agent targeting the gut-liver axis is expected to reverse NAFLD.

Methods: We utilized high-fat diet (HFD)-induced obese mice and obesity-prone Lep mice to examine the gut-liver regulation of the natural medicine Panax Notoginseng Saponins (PNS) on NAFLD.

Results: PNS exhibited potent anti-lipogenesis and anti-fibrotic effects in NAFLD mice, that was associated with the TLR4-induced inflammatory signalling pathway in liver. More strikingly, PNS treatment caused a deceleration of gut-to-liver translocation of microbiota-derived short chain fatty acids (SCFAs) products. PNS-induced TLR4 inhibition and restoration of Claudin-1 and ZO-1 proteins in the gut-liver axis contributed to the reverse of leaky gut, which in turn abolished by the addition of lipopolysaccharide (LPS), an agonist of TLR4. Specifically, hepatic steatosis in HFD-treated mice was attenuated by PNS through regulating AMPKα, but restored by the replenishment of LPS. Meanwhile, the anti-fibrotic effect of PNS was abolished by LPS stimulation via the overproduction of collagen I/IV and α-SMA.

Conclusion: PNS exerted hepatoprotection against NAFLD in both ob/ob and HFD-induced obese mice, primarily by mediating the gut-liver axis in a TLR4-dependent manner. Panax notoginseng saponins (PNS) ameliorated hepatic steatosis and fibrosis, and gut-liver axis-mediated pathogenesis of NAFLD is proposed to occur in a TLR4-dependent manner.
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http://dx.doi.org/10.1007/s12072-021-10138-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144126PMC
April 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

PIWIL1 governs the crosstalk of cancer cell metabolism and immunosuppressive microenvironment in hepatocellular carcinoma.

Signal Transduct Target Ther 2021 02 26;6(1):86. Epub 2021 Feb 26.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.

Altered energy metabolism of cancer cells shapes the immune cell response in the tumor microenvironment that facilitates tumor progression. Herein, we reported the novel of tumor cell-expressed Piwi Like RNA-Mediated Gene Silencing 1 (PIWIL1) in mediating the crosstalk of fatty acid metabolism and immune response of human hepatocellular carcinoma (HCC). PIWIL1 expression in HCC was increased compared to normal hepatic tissues and was positively correlated with the proliferation rate of HCC cell lines. PIWIL1 overexpression accelerated in vitro proliferation and in vivo growth of HCC tumors, while PIWIL1 knockdown showed opposite effects. PIWIL1 increased oxygen consumption and energy production via fatty acid metabolism without altering aerobic glycolysis. Inhibition of fatty acid metabolism abolished PIWIL1-induced HCC proliferation and growth. RNA-seq analysis revealed that immune system regulation might be involved, which was echoed by the experimental observation that PIWIL1-overexpressing HCC cells attracted myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment. MDSCs depletion reduced the proliferation and growth of PIWIL1-overexpressing HCC tumors. Complement C3, whose secretion was induced by PIWIL1 in HCC cells, mediates the interaction of HCC cells with MDSCs by activated p38 MAPK signaling in MDSCs, which in turn initiated expression of immunosuppressive cytokine IL10. Neutralizing IL10 secretion reduced the immunosuppressive activity of MDSCs in the microenvironment of PIWIL1-overexpressing HCC. Taken together, our study unraveled the critical role of PIWIL1 in initiating the interaction of cancer cell metabolism and immune cell response in HCC. Tumor cells-expressed PIWIL1 may be a potential target for the development of novel HCC treatment.
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http://dx.doi.org/10.1038/s41392-021-00485-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907082PMC
February 2021

Chinese Herbal Medicine for Reducing Chemotherapy-Associated Side-Effects in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

Front Oncol 2020 9;10:599073. Epub 2020 Dec 9.

Li Ka Shing Faculty of Medicine, School of Chinese Medicine, The University of Hong Kong, Hong Kong, Hong Kong.

Background: Chemotherapy usually induces a variety of side-effects in cancer treatment as it cannot tell normal cells apart from cancer cells and kills both. Chinese herbal medicine (CHM) has been regarded as a potential effective intervention for relieving the side-effects of chemotherapy in breast cancer patients.

Objective: This study aims to conduct a comprehensive systematic review and meta-analysis to evaluate the efficacy of CHM as adjuvant therapy for reducing the chemotherapy-induced side-effects in the treatment of breast cancer.

Methods: Main electronic databases were searched up to May 2020 for Randomized Controlled Trials (RCTs) evaluating the effect of CHM on breast cancer patients with chemotherapy. The PRISMA statement was adopted in this study and meta-analyses were performed.

Results: The included studies showed unsatisfied quality. Results based on available literature indicated that the adjunctive use of CHM with chemotherapy may reduce the chemotherapeutic agents-associated adverse events, including nausea and vomiting, diarrhea, alopecia, myelosuppression, and impaired immune function.

Conclusion: A confident conclusion could not be have due to the lack of large scale and high quality trials.
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http://dx.doi.org/10.3389/fonc.2020.599073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756083PMC
December 2020

Mental Health Impacts of the COVID-19 Pandemic on International University Students, Related Stressors, and Coping Strategies.

Front Psychiatry 2020 23;11:584240. Epub 2020 Nov 23.

School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted university teaching globally. The mental health impacts on international university students have been overlooked. This study examined the differences in COVID-19-related stressors and mental health impacts between international university students studying in the UK or USA who returned to their home country or region (returnees) and those who stayed in their institution country (stayers), and identified COVID-19-related stressors and coping strategies that were predictors of mental health. An online questionnaire survey was conducted from April 28 through May 12, 2020 using an exponential, non-discriminative snowball sampling strategy (registered at the National Institutes of Health: NCT04365361). A total of 124 full-time international university students (36.3% male) were included: 75.8% had returned to their home country or region for reasons related to COVID-19; 77.4% were pursuing a bachelor's program, and 53.2% were in programs with practicum component. 84.7% of all students had moderate-to-high perceived stress, 12.1% had moderate-to-severe symptoms of anxiety and depression, and 17.7% had moderate-to-severe symptoms of insomnia. Compared with returnees, stayers had significantly higher stress from COVID-19-related stressors such as personal health and lack of social support (Cohen's d: 0.57-1.11), higher perceived stress [10-item Perceived Stress Scale (PSS-10)] {22.6 ± 6.2 vs. 19.1 ± 6.1, β [95% confidence interval (CI)]: 4.039 (0.816, 7.261), Cohen's d: 0.52}, and more severe insomnia symptoms [Insomnia Severity Index (ISI)] [11.8 ± 6.1 vs. 7.6 ± 5.2, β (95% CI): 3.087 (0.262, 5.912), Cohen's d: 0.45], with moderate-to-large effect sizes. Compared with males, females reported significantly higher stress from uncertainties about academic program (Cohen's d: 0.45) with a small effect size. In the total sample, stress related to academics (e.g., personal attainment, uncertainties about academic program, and changes in teaching/learning format), health (including personal health and health of family and friends), availability of reliable COVID-19-related information, and lack of social support predicted more negative mental health impacts. Resilience, positive thinking, and exercise were predictors of less severe mental health impacts. Stayers experienced more adverse mental health impacts than returnees. We call on educators and mental health professionals to provide appropriate support for international students, particularly the stayers, during the pandemic.
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http://dx.doi.org/10.3389/fpsyt.2020.584240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719620PMC
November 2020

Suppression of lncRNA MALAT1 by betulinic acid inhibits hepatocellular carcinoma progression by targeting IAPs via miR-22-3p.

Clin Transl Med 2020 Oct;10(6):e190

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong S.A.R., P. R. China.

Betulinic acid (BA) is a natural product extracted from a broad range of medicinal and edible herbal plants. Previous studies showed that BA induces cell death in tumors derived from multiple tissues; however, the underlying mechanism remains obscure. The present study aimed to study the effects of BA on autophagy and apoptosis of hepatocellular carcinoma (HCC). Human HCC cell lines and orthotopic HCC implanted mice were employed to examine the BA-induced tumor suppression; RT long noncoding RNA (lncRNA) PCR array and database analysis were used to explore the possible mechanisms; validation of pathways was performed using siRNA and miRNA inhibitors. The results indicated that BA regulated autophagy and induced apoptosis in HCC. The degradation of inhibitor of apoptosis proteins (IAPs), the conversion of LC3-I to LC3-II, and p62 accumulation were enhanced by BA, thereby suggesting that the downregulation of IAPs and autophagic cell death are induced by BA. The addition of autophagy and lysosomal inhibitors indicated that BA induced autophagy-independent apoptosis via degradation of IAPs. Moreover, RT lncRNA PCR array and database analysis suggested that BA downregulated the levels of lncRNA MALAT1, which is considered to be an oncogene. Further investigations demonstrated that lncRNA MALAT1 functioned as a ceRNA (competing endogenous RNA) to contribute to BA-mediated degradation of IAPs by sponging miR-22-3p. Therefore, BA could be developed as a potential anticancer agent for HCC.
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http://dx.doi.org/10.1002/ctm2.190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586994PMC
October 2020

Lysyl Oxidase-Like 4 Fosters an Immunosuppressive Microenvironment During Hepatocarcinogenesis.

Hepatology 2021 06 21;73(6):2326-2341. Epub 2021 May 21.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Background And Aims: Lysyl oxidase-like 4 (LOXL4) is an amine oxidase that is primarily involved in extracellular matrix remodeling and is highly expressed in HCC tissues, but its functional role in mediating liver carcinogenesis is poorly understood. Therefore, we aimed to investigate the role of LOXL4 in hepatocarcinogenesis.

Approach And Results: Here, we demonstrate that hepatic LOXL4 expression was increased during the liver carcinogenesis in mice concomitantly fed a choline-deficient, l-amino acid-defined diet. LOXL4 was secreted by the neoplastic cells and primarily localized within hepatic macrophages through exosome internalization. Supplementation of LOXL4 had minimal effect on neoplastic cells. In vitro exposure of macrophages to LOXL4 invoked an immunosuppressive phenotype and activated programmed death ligand 1 (PD-L1) expression, which further suppressed the function of CD8 T cells. Injection of LOXL4 promoted macrophages infiltration into the liver and accelerated tumor growth, which was further abolished by adoptive T-cell transfer or PD-L1 neutralization. Label-free proteomics analysis revealed that the immunosuppressive function of LOXL4 on macrophages primarily relied on interferon (IFN)-mediated signal transducer and activator of transcription-dependent PD-L1 activation. Hydrogen peroxide scavenger or copper chelation on macrophages abolished the IFN-mediated PD-L1 presentation by LOXL4. In human HCC tissue, expression of LOXL4 in CD68 cells was positively correlated with PD-L1 level. High expression of LOXL4 in CD68 cells and low expression of CD8A in tumor tissue cooperatively predict poor survival of patients with HCC.

Conclusions: LOXL4 facilitates immune evasion by tumor cells and leads to hepatocarcinogenesis. Our study unveils the role of LOXL4 in fostering an immunosuppressive microenvironment during hepatocarcinogenesis.
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http://dx.doi.org/10.1002/hep.31600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251926PMC
June 2021

saponins modulate the gut microbiota to promote thermogenesis and beige adipocyte reconstruction leptin-mediated AMPKα/STAT3 signaling in diet-induced obesity.

Theranostics 2020 14;10(24):11302-11323. Epub 2020 Sep 14.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong.

Activation of the thermogenic program in white and brown adipocytes presents a promising avenue for increasing energy expenditure during the treatment of obesity. The endogenous mechanism for promoting thermogenesis in brown adipocytes or browning in white adipocytes has indicated that the gut microbiota is a crucial regulator of the host energy balance. However, whether the effects of the therapeutic intervention-induced modulation of the gut microbiota on adipocyte browning involved the regulation of leptin remains unclear. The adipose features were analyzed by body composition analysis, infrared camera observations, transmission electron microscopy and H&E staining. The gene and protein expression in adipose tissue were detected by qRT-PCR, immunoblotting, immunohistochemistry and immunofluorescence staining. The gut microbiome signature was identified by 16S rRNA gene amplicon sequencing, and both mice with high-fat diet-induced obesity (DIO) and mice with antibiotics-induced microbiome depletion were subjected to fecal microbiota transplantation. Treatment with saponins (PNS) shaped the murine gut microbiome by increasing the abundances of and , and as a result, DIO mice harbored a distal gut microbiota with a significantly increased capacity to reduce host adiposity. The PNS-induced modulation of the gut microbiota in DIO mice could increase brown adipose tissue (BAT) thermogenesis and beige adipocyte reconstruction by activating the leptin-AMPK/STAT3 signaling pathway, which results in the promotion of energy expenditure. Leptin has an essential influence on the anti-obesity effects of PNS. In cases of leptin deficiency, the PNS-induced modulation of the gut microbiota exerts negative effects on thermogenesis and browning in white adipose tissue (WAT), which indicates that PNS fail to reduce obesity in leptin gene-deficient mice. The PNS-induced modulation of the gut microbiota exerted a minimal effect on DIO mice with antibiotic-induced microbiome depletion, which confirmed the correlation between altered gut microbiota and the remodeling of adipose tissues in DIO mice. The direct influence of leptin on browning the AMPKα/STAT3 signaling pathway in C3H101/2 cells supported our results that signalling through the leptin-AMPK/STAT3 pathway induced by the PNS-modulated gut microbiota was involved in beige adipocyte reconstruction. : Our results revealed that leptin signaling is critical for alterations in microbiota-fat crosstalk and provide promising avenues for therapeutic intervention in the treatment of obesity.
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http://dx.doi.org/10.7150/thno.47746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532683PMC
June 2021
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