Publications by authors named "Jingwen Liu"

195 Publications

A study of the differential expression profiles of Keshan disease lncRNA/mRNA genes based on RNA-seq.

Cardiovasc Diagn Ther 2021 Apr;11(2):411-421

Shandong Institute for Endemic Disease Control, Jinan, China.

Background: This study aims to analyze the differential expression profiles of lncRNA in Keshan disease (KSD) and to explore the molecular mechanism of the disease occurrence and development.

Methods: RNA-seq technology was used to construct the lncRNA/mRNA expression library of a KSD group (n=10) and a control group (n=10), and then Cuffdiff software was used to obtain the gene lncRNA/mRNA FPKM value as the expression profile of lncRNA/mRNA. The fold changes between the two sets of samples were calculated to obtain differential lncRNA/mRNA expression profiles, and a bioinformatics analysis of differentially expressed genes was performed.

Results: A total of 89,905 lncRNAs and 20,315 mRNAs were detected. Statistical analysis revealed that 921 lncRNAs had obvious differential expression, among which 36 were up-regulated and 885 were down-regulated; 2,771 mRNAs presented with obvious differential expression, among which 253 were up-regulated and 2,518 were down-regulated, and cluster analysis indicated that the gene expression trends among the sample groups were consistent. The differentially expressed lncRNAs were tested for target genes, and 117 genes were found to be regulated by differential lncRNAs, which were concentrated in six signaling pathways, among which the apoptosis FoxO signaling pathway ranked first, so the target genes and were screened out.

Conclusions: In this study, RNA-seq technology was used to obtain the differential gene expression profiles of KSD, and bioinformatics analysis was performed to screen out target genes, pointing out the direction for further research into the etiology, pathogenesis and drug treatment targets of KSD.
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http://dx.doi.org/10.21037/cdt-20-746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102268PMC
April 2021

Sensitive detection of foodborne pathogens based on CRISPR-Cas13a.

J Food Sci 2021 Apr 30. Epub 2021 Apr 30.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.

Salmonella, being one of the most widespread foodborne pathogens, is a compulsory test item required by national food safety standard of China and many other countries. More sensitive and specific Salmonella detection method is still needed since traditional methods are time consuming and highly dependent on enormous manpower and material resources. In this research, a bacteria detection method based on CRISPR-Cas13a system (where CRISPR is Clustered Regularly Interspaced Short Palindromic Repeats) was proposed. The target DNA was amplified by PCR and transcribed into RNA by T7 transcriptase, which can activate the RNase activity of the Cas13a protein. The self-folding quenched fluorescent probe can be cleaved by the activated Cas13a protein to generate fluorescent signal. We named this method as PCF detection (PCR-CRISPR-Fluorescence based nucleic acid detection). In this study, PCF detection showed excellent sensitivity, which can detect Salmonella genomic DNA with a minimum of 10 aM or 10° CFU/ml Salmonella bacteria in 2 hr. It also showed good specificity with no cross-reaction with other common foodborne bacteria. PRACTICAL APPLICATION: The PCF detection method proposed in this article can detect Salmonella sensitively and specifically, providing a novel strategy for the detection of foodborne pathogens in food and has great application potential in other microbial detection fields.
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http://dx.doi.org/10.1111/1750-3841.15745DOI Listing
April 2021

Peripheral Macrophage-derived Exosomes promote repair after Spinal Cord Injury by inducing Local Anti-inflammatory type Microglial Polarization via Increasing Autophagy.

Int J Biol Sci 2021 30;17(5):1339-1352. Epub 2021 Mar 30.

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated No. 6 People's Hospital, 600 Yishan Road, Shanghai 200233, China.

Treatment for spinal cord injury (SCI) remains a challenge worldwide, and inflammation is a major cause of secondary injury after SCI. Peripheral macrophages (PMs) have been verified as a key factor that exert anti-inflammatory effects after SCI, but the mechanism is unidentified. As local macrophages, microglia also exert significant effects after SCI, especially polarization. Exosomes show source cell-like biological functions to target cells and have been the subject of much research in recent years. Thus, we hypothesized the PM-derived exosomes (PM-Exos) play an important role in signal transmission with local microglia and can be used therapeutic agents for SCI in a series of and studies. For the experiment, three groups of Sprague-Dawley (SD) rats subjected to spinal cord contusion injury were injected with 200 µg/ml PM-Exos, 20 µg/ml PM-Exos or PBS via the tail vein. Recovery of the rats and of spinal cord function were observed. , we investigated the potential anti-inflammatory mechanism of PM-Exos and evaluated microglial autophagy, anti-inflammatory type microglia polarization and the upstream signaling pathway. The results showed that spinal cord function and recovery were better in the PM-Exo groups than the control group. In the study, microglial autophagy levels and the expression of anti-inflammatory type microglia were higher in the experimental groups than the control group. Moreover, the expression of proteins related to the PI3K/AKT/mTOR autophagic signaling pathway was suppressed in the PM-Exo groups. PM-Exos have a beneficial effect in SCI, and activation of microglial autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway, enhancing the polarization of anti-inflammatory type microglia, that may play a major role in the anti-inflammatory process.
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http://dx.doi.org/10.7150/ijbs.54302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040463PMC
March 2021

Injectable composite hydrogel promotes osteogenesis and angiogenesis in spinal fusion by optimizing the bone marrow mesenchymal stem cell microenvironment and exosomes secretion.

Mater Sci Eng C Mater Biol Appl 2021 Apr 17;123:111782. Epub 2021 Feb 17.

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated No.6 People's Hospital, 600 Yishan Road, Shanghai 200233, China. Electronic address:

With the development of tissue engineering, it is no longer a challenge to repair and reconstruct bone defects using bone substitutes. However, in spinal fusion surgery, high rates of fusion failure are difficult to avoid. In our study, we designed a new composite hydrogel and found that it has good osteogenesis and angiogenesis effects. We extracted exosomes produced by rBMSCs (rat bone marrow mesenchymal stem cells) cocultured with the hydrogel to investigate their effects on osteogenesis and angiogenesis. The results showed that the PG/TCP (PEGMC with β-TCP) promoted rapid osteogenesis, facilitated spinal fusion at a high rate and quality and had an indirect effect on angiogenesis. We found that PG/TCP affected the rBMSC microenvironment, thus changing the function of exosomes; in a further study, we found that PG/TCP-MSC-Exos played a significant role in osteogenesis, which was coupled to angiogenesis. Thus, PG/TCP showed excellent potential in bone regeneration, especially the PG/0.2TCP.
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http://dx.doi.org/10.1016/j.msec.2020.111782DOI Listing
April 2021

2-arachidonoylglycerol might be a novel therapeutic target in the treatment of cardiovascular disease.

Int J Cardiol 2021 Jun 31;332:162. Epub 2021 Mar 31.

Department of Cardiology, The Second People's Hospital of Liaocheng, Liaocheng 252000, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2021.03.075DOI Listing
June 2021

Co-Amorphous Drug Formulations in Numbers: Recent Advances in Co-Amorphous Drug Formulations with Focus on Co-Formability, Molar Ratio, Preparation Methods, Physical Stability, In Vitro and In Vivo Performance, and New Formulation Strategies.

Pharmaceutics 2021 Mar 15;13(3). Epub 2021 Mar 15.

Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.

Co-amorphous drug delivery systems (CAMS) are characterized by the combination of two or more (initially crystalline) low molecular weight components that form a homogeneous single-phase amorphous system. Over the past decades, CAMS have been widely investigated as a promising approach to address the challenge of low water solubility of many active pharmaceutical ingredients. Most of the studies on CAMS were performed on a case-by-case basis, and only a few systematic studies are available. A quantitative analysis of the literature on CAMS under certain aspects highlights not only which aspects have been of great interest, but also which future developments are necessary to expand this research field. This review provides a comprehensive updated overview on the current published work on CAMS using a quantitative approach, focusing on three critical quality attributes of CAMS, i.e., co-formability, physical stability, and dissolution performance. Specifically, co-formability, molar ratio of drug and co-former, preparation methods, physical stability, and in vitro and in vivo performance were covered. For each aspect, a quantitative assessment on the current status was performed, allowing both recent advances and remaining research gaps to be identified. Furthermore, novel research aspects such as the design of ternary CAMS are discussed.
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http://dx.doi.org/10.3390/pharmaceutics13030389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999207PMC
March 2021

Is there an association between hot weather and poor mental health outcomes? A systematic review and meta-analysis.

Environ Int 2021 Mar 30;153:106533. Epub 2021 Mar 30.

School of Public Health, The University of Adelaide, Australia. Electronic address:

Background: Mental health is an important public health issue globally. A potential link between heat exposure and mental health outcomes has been recognised in the scientific literature; however, the associations between heat exposure (both high ambient temperatures and heatwaves) and mental health-related mortality and morbidity vary between studies and locations.

Objective: To fill gaps in knowledge, this systematic review aims to summarize the epidemiological evidence and investigate the quantitative effects of high ambient temperatures and heatwaves on mental health-related mortality and morbidity outcomes, while exploring sources of heterogeneity.

Methods: A systematic search of peer-reviewed epidemiological studies on heat exposure and mental health outcomes published between January 1990 and November 2020 was conducted using five databases (PubMed, Embase, Scopus, Web of Science and PsycINFO). We included studies that examined the association between high ambient temperatures and/or heatwaves and mental health-related mortality and morbidity (e.g. hospital admissions and emergency department visits) in the general population. A range of mental health conditions were defined using ICD-10 classifications. We performed random effects meta-analysis to summarize the relative risks (RRs) in mental health outcomes per 1 °C increase in temperature, and under different heatwaves definitions. We further evaluated whether variables such as age, sex, socioeconomic status, and climate zone may explain the observed heterogeneity.

Results: The keyword search yielded 4560 citations from which we identified 53 high temperatures/heatwaves studies that comprised over 1.7 million mental health-related mortality and 1.9 million morbidity cases in total. Our findings suggest associations between heat exposures and a range of mental health-related outcomes. Regarding high temperatures, our meta-analysis of study findings showed that for each 1 °C increase in temperature, the mental health-related mortality and morbidity increased with a RR of 1.022 (95%CI: 1.015-1.029) and 1.009 (95%CI: 1.007-1.015), respectively. The greatest mortality risk was attributed to substance-related mental disorders (RR, 1.046; 95%CI: 0.991-1.101), followed by organic mental disorders (RR, 1.033; 95%CI: 1.020-1.046). A 1 °C temperature rise was also associated with a significant increase in morbidity such as mood disorders, organic mental disorders, schizophrenia, neurotic and anxiety disorders. Findings suggest evidence of vulnerability for populations living in tropical and subtropical climate zones, and for people aged more than 65 years. There were significant moderate and high heterogeneities between effect estimates in overall mortality and morbidity categories, respectively. Lower heterogeneity was noted in some subgroups. The magnitude of the effect estimates for heatwaves varied depending on definitions used. The highest effect estimates for mental health-related morbidity was observed when heatwaves were defined as "mean temperature ≥90th percentile for ≥3 days" (RR, 1.753; 95%CI: 0.567-5.421), and a significant effect was also observed when the definition was "mean temperature ≥95th percentile for ≥3 days", with a RR of 1.064 (95%CI: 1.006-1.123).

Conclusions: Our findings support the hypothesis of a positive association between elevated ambient temperatures and/or heatwaves and adverse mental health outcomes. This problem will likely increase with a warming climate, especially in the context of climate change. Further high-quality studies are needed to identify modifying factors of heat impacts.
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http://dx.doi.org/10.1016/j.envint.2021.106533DOI Listing
March 2021

HSP25 Vaccination Attenuates Atherogenesis via Upregulation of LDLR Expression, Lowering of PCSK9 Levels and Curbing of Inflammation.

Arterioscler Thromb Vasc Biol 2021 Apr 1:ATVBAHA121315933. Epub 2021 Apr 1.

Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary Cumming School of Medicine, Alberta, Canada (Y.-X.C., C.S., J.D., C.D., N.M., M.R., V.S., A.A.H., S.B., A.A., A.U.-L., B.G., Z.B., E.R.O.).

Objective: Elevated HSP27 (heat shock protein 27) levels predict relative freedom from cardiovascular events. Over-expression or twice daily subcutaneous injections of human HSP27 in mice reduces blood and plaque cholesterol levels, as well as inflammation and atherosclerotic plaque burden. Antibodies to HSP27 are present in human blood, and the purpose of the current studies is to explore their role. Approach and Results: Blood levels of both HSP27 and anti-HSP27 IgG antibodies are elevated in healthy controls compared with patients with cardiovascular disease. mice fed a high-fat diet and vaccinated with recombinant HSP25 (rHSP25, murine ortholog) show increased levels of anti-HSP25 IgG antibodies and reductions in plasma cholesterol and atherogenesis. Moreover, rHSP25 vaccination markedly lowered serum amyloid A levels as well as hepatic macrophage abundance and inflammatory cytokine expression. The effects of the HPS25 vaccination on cholesterol metabolism are divergent: increased hepatic LDLR (low-density lipoprotein receptor) mRNA and protein expression and reduced plasma PCSK9 (proprotein convertase subtilisin/kexin type 9) levels-despite no effect on PCSK9 expression. In vitro, the HSP27 immune complex upregulates hepatocyte LDLR mRNA and protein expression independent of intracellular cholesterol levels and increases LDLR promoter activity. The increase in LDLR expression by the HSP27 immune complex is dependent upon activation of the NF-κB (nuclear factor κ light chain enhancer of activated B cells) pathway. Hepatocyte PCSK9 protein levels are reduced after HSP27 immune complex treatment in vitro despite only minor transient effects on gene expression.

Conclusions: HSP27 immunotherapy represents a novel means of lowering cholesterol and PCSK9 levels, primarily due to augmentation of LDLR expression and is associated with marked reductions in inflammation.
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http://dx.doi.org/10.1161/ATVBAHA.121.315933DOI Listing
April 2021

Reference values for lower limb nerve ultrasound and its diagnostic sensitivity.

J Clin Neurosci 2021 Apr 20;86:276-283. Epub 2021 Feb 20.

Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China. Electronic address:

We aimed to establish the cross-sectional area (CSA) reference values for peripheral nerves of lower extremities in a healthy Chinese population, and to determine their diagnostic values for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Charcot-Marie-Tooth disease type1A (CMT1A). One hundred eleven healthy subjects, 15-70 years of age, as well as 104 CIDP patients and 26 CMT1A patients were recruited. CSA at predetermined sites of the tibial, fibular, sciatic and sural nerves was measured. The CSA of the tibial nerve ranged from 10.2 ± 1.9 to 20.7 ± 3.6 mm, and for fibular nerve from 8.4 ± 1.8 to 9.5 ± 1.9 mm. 86% CIDP patients had upper limb nerve enlargement, while only 67% had lower limb nerve enlargement. In CIDP patients with normal upper limb ultrasound, 56% (5/9) would have lower limb nerve enlargement. All CMT1A patients had both upper and lower limb nerve enlargement. Addition of lower limb nerve ultrasound showed no added value in diagnosis of CMT1A, but could be supplementary for CIDP when upper limb ultrasound is normal.
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http://dx.doi.org/10.1016/j.jocn.2021.01.013DOI Listing
April 2021

Targeting mitochondrial calcium uniporter in heart failure.

Int J Cardiol 2021 Jun 16;333:187. Epub 2021 Mar 16.

Department of Cardiology, Liaocheng People(')s Hospital, Liaocheng 252000, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2021.03.028DOI Listing
June 2021

Acellular fish skin enhances wound healing by promoting angiogenesis and collagen deposition.

Biomed Mater 2021 Apr 9;16(4). Epub 2021 Apr 9.

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, People's Republic of China.

Acellular matrix is a type of promising biomaterial for wound healing promotion. Although acellular bovine and porcine tissues have proven effective, religious restrictions and risks of disease transmission remain barriers to their clinical use. Acellular fish skin (AFS), given its similarity to human skin structure and without the aforementioned disadvantages, is thus seen as an attractive alternative. This study aims to fabricate AFS from the skin of black carp (), evaluate its physical and mechanical properties and assess its impact on wound healing. The results showed that AFS has a highly porous structure, along with high levels of hydrophilicity, water-absorption property and permeability. Furthermore, physical characterization showed the high tensile strength of AFS in dry and wet states, and high stitch tear resistance, indicating great potential in clinical applications. Cell Counting Kit-8 was used to test the viability of L929 cells when culturing in the extracts of AFS. Compared with the control group, there is no significant difference in optical density value when culturing in the extracts of AFS at days 1, 3 and 7 (*> 0.05).wound healing evaluation then highlighted its promotion of angiogenesis and collagen synthesis, its function in anti-inflammation and acceleration in wound healing. Therefore, this study suggests that AFS has potential as a promising alternative to mammal-derived or traditional wound dressing.
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http://dx.doi.org/10.1088/1748-605X/abef7aDOI Listing
April 2021

Isostructural Single- And Dual-Lanthanide Metal-Organic Frameworks Based On Substituent-Group-Modifying Tetracarboxylate Ligands for Ratiometric Temperature Sensing.

Inorg Chem 2021 Mar 4;60(6):4133-4143. Epub 2021 Mar 4.

Institute of Frontier and Interdisciplinarity Science and Institute of Molecular Sciences and Engineering, Shandong University, Qingdao 266237, China.

In this study, two substituent-group-modifying tetracarboxylate ligands, 2',5'-dimethoxy-[1,1':4',1″-terphenyl]-3,3″,5,5″-tetracarboxylic acid (HTPTC-2OMe) and 2',5'-dimethyl-[1,1':4',1″-terphenyl]-3,3″,5,5″-tetracarboxylic acid (HTPTC-2Me), with similar geometries were used as the organic linkers to construct isostructural lanthanide metal-organic frameworks (LnMOFs). The as-prepared LnTPTC-2OMe and LnTPTC-2Me were structurally elucidated by means of single-crystal and powder X-ray diffraction in addition to thermogravimetric analysis and were assessed as luminescence ratiometric thermometers by obtaining the temperature dependence of the luminescence behaviors. We found that both the single lanthanide EuTPTC-2OMe and the dual lanthanide EuTbTPTC-2Me exhibited a distinct S-type luminescence response to temperatures in the range from 313 to 473 K, and their ratiometric parameters can be understood on the basis of the classic Mott-Seitz model. Energy transfers from the ligand to Tb (or Eu) and from Tb to Eu in these two systems were investigated theoretically as well as with low-temperature (77 K) time-resolved photoluminescence spectroscopy, quantum yield, and lifetime analysis. Therefore, these two materials possess a good relative sensitivity, a small temperature uncertainty, and a favorable spectral repeatability in addition to a remarkable emission color change, enhancing their potential use for temperature measurement and in situ monitoring in microelectronics.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00310DOI Listing
March 2021

Embedding Red Emitters in the NbO-Type Metal-Organic Frameworks for Highly Sensitive Luminescence Thermometry over Tunable Temperature Range.

ACS Appl Mater Interfaces 2021 Mar 26;13(9):11078-11088. Epub 2021 Feb 26.

Department of Chemistry, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249-0698, United States.

The intrinsic advantages of metal-organic frameworks (MOFs), including extraordinarily high porosities, tailorable architectures, and diverse functional sites, make the MOFs platforms for multifunctional materials. In this study, we synthesized two kinds of isostructural NbO-type Zn-based MOFs, where two structurally similar tetracarboxylate ligands, 5,5'-(pyrazine-2,5-diyl)diisophthalic acid (HPZDDI) and 5,5'-(pyridine-2,5-diyl)diisophthalic acid (HPDDI), with pyridine or pyrazine moieties, were employed as the organic linkers. By embedding the red-emitting cationic units of pyridinium hemicyanine dye 4-[p-(dimethylamino)styryl]-1-methylpyridinium (DSM) and trivalent europium ion (Eu), two types of composites, DSM@ZnPZDDI and DSM@ZJU-56 and Eu@ZnPZDDI and Eu@ZJU-56, were harvested and evaluated for use as potential ratiometric temperature probes. The temperature-responsive luminescence of these dual-emitting composites was investigated, and their representative features of relative sensitivity, temperature resolution, spectral repeatability, and luminescence color change were discussed. Importantly, compared with the DSM-incorporated composites, Eu@ZnPZDDI and Eu@ZJU-56 show a much wider sensing temperature range and higher relative sensitivities, suggesting the performance of the composites can be engineered by elaborately combining the host and guest units. Given the rich choices of porous MOFs and emitting units, such a strategy can be useful in the design and preparation of multifunctional dual-emitting sensory materials.
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http://dx.doi.org/10.1021/acsami.1c00635DOI Listing
March 2021

Combined Effect of the Preparation Method and Compression on the Physical Stability and Dissolution Behavior of Melt-Quenched Amorphous Celecoxib.

Mol Pharm 2021 03 15;18(3):1408-1418. Epub 2021 Feb 15.

The Dodd-Walls Centre for Photonic and Quantum Technologies, Department of Chemistry, University of Otago, Dunedin 9016, New Zealand.

In an earlier investigation, amorphous celecoxib was shown to be sensitive to compression-induced destabilization. This was established by evaluating the physical stability of uncompressed/compressed phases in the supercooled state (Be̅rziņš . , 2019, 16(8), 3678-3686). In this study, we investigated the ramifications of compression-induced destabilization in the glassy state as well as the impact of compression on the dissolution behavior. Slow and fast melt-quenched celecoxib disks were compressed with a range of compression pressures (125-500 MPa) and dwell times (0-60 s). These were then monitored for crystallization using low-frequency Raman spectroscopy when kept under dry (∼20 °C; <5% RH) and humid (∼20 °C; 97% RH) storage conditions. Faster crystallization was observed from the samples, which were compressed using more severe compression parameters. Furthermore, crystallization was also affected by the cooling rate used to form the amorphous phases; slow melt-quenched samples exhibited higher sensitivity to compression-induced destabilization. The behavior of the melt-quench disks, subjected to different compression conditions, was continuously monitored during dissolution using low-frequency Raman and UV/vis for the solid-state form and dissolution properties, respectively. Surprisingly the compressed samples exhibited higher apparent dissolution (i.e., higher area under the dissolution curve and initial celecoxib concentration in solution) than the uncompressed samples; however, this is attributed to biaxial fracturing throughout the compressed compacts yielding a greater effective surface area. Differences between the slow and fast melt quenched samples showed some trends similar to those observed for their storage stability.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c01208DOI Listing
March 2021

Duration of SARS-CoV-2 positive in quarantine room environments: A perspective analysis.

Int J Infect Dis 2021 Apr 10;105:68-74. Epub 2021 Feb 10.

Department of Public Health Emergency Response, Guangzhou Center for Disease Control and Prevention, Baiyun District Qi De Road in Guangzhou, Guangdong Province, 510440, China. Electronic address:

Objective: To determine the duration of SARS-CoV-2 persistence in quarantine hotel environments.

Methods: 39 Patients confirmed by RT-PCR were included. We collected clinical features, laboratory test results, smear sample information, and quarantine room information. Genome sequencing and phylogenetic analysis were conducted. We analyzed the factors associated with environmental contamination.

Result: Among 39 COVID-19 cases, 10 were asymptomatic and 37 were imported from aboard. We collected 271 swab samples from environmental surfaces related to observational patients. Eighteen swab samples from seven patients were positive. The highest contamination rates occurred on cups (100%), followed by hand sink (12.82%), toilet seat and flush (7.89%), telephone (5.56%), bedside table (5.56%), and floor drain (5.41%). The results showed that environmental surface contamination was associated with the clinical cycle threshold values for patients (P = 0.01) and the sampling interval time after the cases left their rooms (P = 0.03). The duration of environmental surface contamination was associated with the wet status of the sampling site (P = 0.01).

Conclusion: Our findings showed that environmental contamination might be attributed to the viral load in the respiratory tracts of patients and the sampling interval time after the cases left their rooms. Moist surfaces were more vulnerable to remaining SARS-CoV-2 RNA-positive. Our study highlights the importance of implementing strict chemical disinfection strategies in quarantine rooms.
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http://dx.doi.org/10.1016/j.ijid.2021.02.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872842PMC
April 2021

Three Novel Dietary Phenolic Compounds from Pickled Raphanus Sativus L. Inhibit Lipid Accumulation in Obese Mice by Modulating the Gut Microbiota Composition.

Mol Nutr Food Res 2021 03 25;65(6):e2000780. Epub 2021 Feb 25.

Fujian Provincial Engineering Technology Research Center of Marine Functional Food, College of Food and Biological Engineering, Jimei University, Xiamen, 361021, China.

Scope: Although pickled radish is widely consumed worldwide, few studies have investigated the nutritional benefits of bioactive compounds extracted from pickled radish. In this study, the authors investigate the relationship among dietary phenolic compounds, lipid accumulation, and gut microbiota.

Method And Results: Three phenolic compounds 2,6-dihydroxyacetophenone (DHAP), 4-hydroxyphenethyl alcohol (4-HPEA), and 4-hydroxybenzaldehyde (HBA) are extracted from pickled radish. LO2 cells treated with free fatty acid are first used to explore the impact of the above three compounds at different doses on reducing lipid levels. The effects of the three compounds on obesity and the gut microbiota are further investigated in high-fat diet (HFD)-induced KM mice. Results show that three compounds inhibited the lipid accumulation in LO2 cells. The results of animal experiments reveal that three compounds prevented body weight gain and significantly decreased serum lipid levels. Treatment with DHAP, HPEA, and HBA reversed gut microbiome dysbiosis in HFD-induced mice. The three phenolic compounds increase Odoribacter, and decrease Helicobacter and Mucispirillum. Notably, DHAP and HBA reduce the HFD-induced increase in the Firmicutes/Bacteroidetes ratio.

Conclusion: These data suggest that phenolic compounds extracted from pickled radish possess excellent lipid-lowering capacity, providing a theoretical basis for further analysis of the nutritional value of pickled radish.
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http://dx.doi.org/10.1002/mnfr.202000780DOI Listing
March 2021

A Multivariate Approach for the Determination of the Optimal Mixing Ratio of the Non-Strong Interacting Co-Amorphous System Carvedilol-Tryptophan.

Molecules 2021 Feb 4;26(4). Epub 2021 Feb 4.

Department of Pharmacy, University of Copenhagen, DK-2100 Copenhagen, Denmark.

Converting crystalline compounds into co-amorphous systems is an effective way to improve the solubility of poorly water-soluble drugs. It is, however, of critical importance for the physical stability of co-amorphous systems to find the optimal mixing ratio of the drug with the co-former. In this study, a novel approach for this challenge is presented, exemplified with the co-amorphous system carvedilol-tryptophan (CAR-TRP). Following X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) of the ball-milled samples to confirm their amorphous form, Fourier-transform infrared spectroscopy (FTIR) and principal component analysis (PCA) were applied to investigate intermolecular interactions. A clear deviation from a purely additive spectrum of CAR and TRP was visualized in the PCA score plot, with a maximum at around 30% drug (mol/mol). This deviation was attributed to hydrogen bonds of CAR with TRP ether groups. The sample containing 30% drug (mol/mol) was also the most stable sample during a stability test. Using the combination of FTIR with PCA is an effective approach to investigate the optimal mixing ratio of non-strong interacting co-amorphous systems.
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http://dx.doi.org/10.3390/molecules26040801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913994PMC
February 2021

A novel prognostic nomogram for colorectal cancer liver metastasis patients with recurrence after hepatectomy.

Cancer Med 2021 03 4;10(5):1535-1544. Epub 2021 Feb 4.

State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

Purpose: We aimed to construct a nomogram to predict personalized post-recurrence survival (PRS) among colorectal cancer liver metastasis (CRLM) patients with post-hepatectomy recurrence.

Methods: Colorectal cancer liver metastasis patients who received initial hepatectomy and had subsequent recurrence between 2001 and 2019 in Sun Yat-sen University Cancer Center from China were included in the study. Patients were randomly assigned to a training cohort and a validation cohort on a ratio of 2:1. Univariable analysis was first employed to select potential predictive factors for PRS. Then, the multivariable Cox regression model was applied to recognize independent prognostic factors. According to the model, a nomogram to predict PRS was established. The nomogram's predictive capacity was further assessed utilizing concordance index (C-index) values, calibration plots, and Kaplan-Meier curves.

Results: About 376 patients were finally enrolled, with a 3-year PRS rate of 37.3% and a 5-year PRS rate of 24.6%. The following five independent predictors for PRS were determined to construct the nomogram: the largest size of liver metastases at initial hepatectomy, relapse-free survival, CEA level at recurrence, recurrent sites, and treatment for recurrence. The nomogram displayed fairly good discrimination and calibration. The C-index value was 0.742 for the training cohort and 0.773 for the validation cohort. Patients were grouped into three risk groups very well by the nomogram, with 5-year PRS rates of 45.2%, 23.3%, and 9.0%, respectively (p < 0.001) in the training cohort and 36.0%, 9.2%, and 4.6%, respectively (p < 0.001) in the validation cohort.

Conclusion: A novel nomogram was built and validated to enable the prediction of personal PRS in CRLM patients with post-hepatectomy recurrence. The nomogram may help physicians in decision making.
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http://dx.doi.org/10.1002/cam4.3697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940234PMC
March 2021

Using ecological variables to predict Ross River virus disease incidence in South Australia.

Trans R Soc Trop Med Hyg 2021 Feb 3. Epub 2021 Feb 3.

School of Public Health, The University of Adelaide, Adelaide, Australia.

Background: Ross River virus (RRV) disease is Australia's most widespread vector-borne disease causing significant public health concern. The aim of this study was to identify the ecological covariates of RRV risk and to develop epidemic forecasting models in a disease hotspot region of South Australia.

Methods: Seasonal autoregressive integrated moving average models were used to predict the incidence of RRV disease in the Riverland region of South Australia, an area known to have a high incidence of the disease. The model was developed using data from January 2000 to December 2012 then validated using disease notification data on reported cases for the following year.

Results: Monthly numbers of the mosquito Culex annulirostris (β=0.033, p<0.001) and total rainfall (β=0.263, p=0.002) were significant predictors of RRV transmission in the study region. The forecasted RRV incidence in the predictive model was generally consistent with the actual number of cases in the study area.

Conclusions: A predictive model has been shown to be useful in forecasting the occurrence of RRV disease, with increased vector populations and rainfall being important factors associated with transmission. This approach may be useful in a public health context by providing early warning of vector-borne diseases in other settings.
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http://dx.doi.org/10.1093/trstmh/traa201DOI Listing
February 2021

Epidermal growth factor/epidermal growth factor receptor moves into the osteoblasts' cell nuclei where it is involved to regulate STAT5's signaling.

Biofactors 2021 Jan 27. Epub 2021 Jan 27.

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Epidermal growth factor (EGF) has vital biological impacts on the osteoblasts. However, the knowledge on the cellular properties of EGF/EGFR (epidermal growth factor receptor) on osteoblasts is scanty. As such, we explored the EGF/EGFR's cell behavior in the osteoblast (MC3T3-E1 cell) using the indirect immunofluorescence assay, Western-blot, and fluorescence resonance energy transfer. Our findings revealed that EGF could internalize into the cytoplasm under EGFR mediation. Besides, the co-localization analysis demonstrated that caveolin played a critical role in EGFR's endocytosis. We also analyzed the cytoplasmic trafficking pathway of EGF/EGFR in MC3T3-E1 cell. The colocalization analysis showed that EGFR entered into Rab5, Rab4, and Rab9-positive endosomes. More importantly, we found that EGFR could move into the MC3T3-E1 cells' nuclei. Based on this, we investigated the EGFR's nuclear-localized functions, and the results suggested that nuclear-localized EGFR has important biological functions. This work lays a foundation for further study on EGF/EGFR's biological functions on the osteoblasts.
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http://dx.doi.org/10.1002/biof.1709DOI Listing
January 2021

Antioxidant Activity of Docosahexaenoic Acid (DHA) and Its Regulatory Roles in Mitochondria.

J Agric Food Chem 2021 Feb 26;69(5):1647-1655. Epub 2021 Jan 26.

College of Food and Biological Engineering, Jimei University, No. 43 Yindou Road, Jimei District, Xiamen, Fujian 361021, P. R. China.

Reactive oxygen species (ROS) are single-electron-bearing oxidation-reduction products that are mainly produced in mitochondria. Excessive ROS accumulation may lead to oxidative damage. Docosahexaenoic acid (DHA) is an essential component of brain phospholipids and is mainly derived from the diet. Its antioxidant activities have been extensively studied. However, its regulatory roles in mitochondria and the underlying mechanism remain to be elucidated. In this study, the DHA's effect on cellular antioxidant capacity and mitochondrial functions was examined in HepG2 cells. The results showed that 100 μM DHA decreased cellular and mitochondrial ROS levels to 75.2 ± 9.4% ( < 0.05) and 55.1 ± 1.4% ( < 0.01), respectively. It also increased the total antioxidant capacity by 55.6 ± 0.1 and 49.2 ± 1.1% ( < 0.05), based on ABTS and FRAP assay results, respectively. Consistently, it increased the activities and gene expression of major antioxidant enzymes by at least 35 and 40% ( < 0.05), respectively. Furthermore, DHA promoted mitochondrial functions and biogenesis. These data suggested that DHA's antioxidant activity can be attributed to its enhancement of mitochondrial functions and biogenesis. This study may shed light on the molecular mechanisms underlying DHA's function in improving resistance to and relieving the symptoms of chronic disease.
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http://dx.doi.org/10.1021/acs.jafc.0c07751DOI Listing
February 2021

Targeting microRNA-135b in cardiac hypertrophy.

Int J Cardiol 2021 Apr 4;329:176. Epub 2021 Jan 4.

Department of Intensive Care Unit, Liaocheng People(')s Hospital, Liaocheng 252000, PR China.. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2020.12.083DOI Listing
April 2021

Cytokines/Chemokines: Potential Biomarkers for Non-paraneoplastic Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

Front Neurol 2020 21;11:582296. Epub 2020 Dec 21.

Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common type of autoimmune encephalitis. This study focuses on finding new biomarkers to evaluate the clinical condition and provide new directions for treatment. A total of 44 cytokines/chemokines in the cerebrospinal fluid of 10 non-paraneoplastic patients and nine controls were measured. We selected some of the cytokines/chemokines that significantly increased in patients. Six selected cytokines/chemokines, including IL-10, CXCL10, CCL22, CCL3, IL-7, TNF-α, and three previously reported (IL-2, IL-6, and IL-17A), were measured in seven other patients who provided repeat samples. We compared their levels and explored correlations with severity of disease and antibody titers. The levels of Th1 axis (CXCL10, TNF-α, IFN-γ, CCL3), Th2 axis (CCL1, CCL8, CCL17, CCL22), Treg axis (IL-10), Th17 axis (IL-7), and B cell axis (CXCL13) cytokines, as well as IL-12 p40 and IL-16, were significantly higher in patients compared to those in controls. The level of IL-2 was significantly decreased at the intermediate stage of treatment compared with that before treatment. The severity of disease is positively correlated with levels of CXCL10, CCL3, IL-10, CCL22, and IL-6. The level of CCL3 in the high antibody titer group was greater than that in the low antibody titer group. The pathogenesis of anti-NMDAR encephalitis involves T cell and B cell cytokines. T cells likely assist B cells to produce antibodies. IL-2, CXCL10, CCL3, IL-10, CCL22, and IL-6 may represent new biomarkers in anti-NMDAR encephalitis. Given the lack of research on IL-10, CCL3, and CCL22 in this disease, it will be informative to explore their potential role in pathogenesis in larger studies.
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http://dx.doi.org/10.3389/fneur.2020.582296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779630PMC
December 2020

Split phenomenon of antagonistic muscle groups in amyotrophic lateral sclerosis: relative preservation of flexor muscles.

Neurol Res 2021 May 29;43(5):372-380. Epub 2020 Dec 29.

Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

: In addition to the split hand sign, other split phenomena of different muscles also exist in amyotrophic lateral sclerosis (ALS). We analyzed the incidence of split phenomena in multiple antagonistic muscle groups in ALS patients and explored whether clinical factors affected their occurrence.: 618 ALS patients were included from a single ALS center. Muscle strength in upper and lower limbs was evaluated using the modified Medical Research Council (MRC) scoring system (range from 1 to 13). Split phenomena between different antagonistic muscle groups were summarized, and the correlations with clinical factors were analyzed.: Split phenomena were detected in 22.3% antagonistic muscles for flexion and extension of the elbow, 11.9% for the wrist, 23.9% for fingers, 18.2% for the ankle, and 14.7% for toes. These manifestations were characterized by preferential wasting of the elbow, wrist, and finger extensor muscles compared with the flexor muscles, and the ankle and toe dorsiflexor muscles compared with the plantar flexor muscles. The presence of muscle wasting was more common when the muscle strength was stronger than a modified MRC grade 6. No definite correlation was found between split phenomena and clinical factors, including age-at-onset, gender, disease duration, the region of onset, and pyramidal tract damage.: Split phenomena of antagonistic muscle groups widely exist in ALS patients. No definitive and consistent clinical factors were observed that affected the occurrence of these phenomena.
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http://dx.doi.org/10.1080/01616412.2020.1866354DOI Listing
May 2021

Naringin attenuates cisplatin- and aminoglycoside-induced hair cell injury in the zebrafish lateral line via multiple pathways.

J Cell Mol Med 2021 Jan 3;25(2):975-989. Epub 2020 Dec 3.

Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Exposure to ototoxic drugs is a significant cause of hearing loss that affects about 30 thousand children with potentially serious physical, social and psychological dysfunctions every year. Cisplatin (CP) and aminoglycosides are effective antineoplastic or bactericidal drugs, and their application has a high probability of ototoxicity which results from the death of hair cells (HCs). Here, we describe the therapeutic effect of the flavonoid compound naringin (Nar) against ototoxic effects of cisplatin and aminoglycosides include gentamicin (GM) and neomycin (Neo) in zebrafish HCs. Animals incubated with Nar (100-400 μmol/L) were protected against the pernicious effects of CP (150-250 μmol/L), GM (50-150 μmol/L) and Neo (50-150 μmol/L). We also provide evidence for the potential mechanism of Nar against ototoxicity, including antioxidation, anti-apoptosis, promoting proliferation and hair cell regeneration. We found that mRNA levels of the apoptotic- and pyroptosis-related genes are regulated by Nar both in vivo and in vitro. Finally, by proving that Nar does not affect the anti-tumour efficacy of CP and antibacterial activity of aminoglycosides in vitro, we highlight its value in clinical application. In conclusion, these results unravel a novel therapeutic role for Nar as an otoprotective drug against the adverse effects of CP and aminoglycosides.
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http://dx.doi.org/10.1111/jcmm.16158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812295PMC
January 2021

Implantation of Foldable Capsular Vitreous Body for the Treatment of Acute Retinal Necrosis Syndrome: A Case Report.

Ophthalmic Surg Lasers Imaging Retina 2020 11;51(11):653-657

The authors present the case of a 35-year-old male who was diagnosed with acute retinal necrosis syndrome that evolved into retinal detachment (RD), even after immediate treatment with systemic antiviral medications, as well as intravitreal injection and laser photocoagulation. Pars plana vitrectomy plus silicone oil tamponade was performed, but silicone oil emulsified 22 months later. Due to the widespread necrosis lesions and defects of the peripheral retina, RD was highly likely to reoccur after silicone oil removal; thus, foldable capsular vitreous body was implanted to support the retina. No recurrent RD was observed afterward. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:653-657.].
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http://dx.doi.org/10.3928/23258160-20201104-09DOI Listing
November 2020

Target genetic abnormalities for the treatment of colon cancer and its progression to metastasis.

Curr Drug Targets 2020 Nov 19. Epub 2020 Nov 19.

SVKM's DR. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai. India.

Colorectal carcinogenesis involves various processes from the accumulation of genetic alterations to genetic and epigenetic modulations and chromosomal abnormalities. It also involves mutations in oncogenes and tumour suppressor genes. Genomic instability plays a vital role in CRC. Advances in modern biological techniques and molecular level studies have identified various genes that are involved in colorectal cancer (CRC). KRAS, BRAF, PI3K, and p53 genes play a significant role in different phases of CRC. Alteration of these genes leads to development or progression and metastasis colon cancer. This review focuses on the role of KRAS, BRAF, PI3KCA, and TP53 genes in carcinogenesis and their significance in various stages of CRC. It also provides insights on specific modulators acting on these genes. Further, this review discusses the mechanism of the pathways involving these genes in carcinogenesis and current molecules and treatment options under various stages of clinical evaluation.
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http://dx.doi.org/10.2174/1389450121666201119141015DOI Listing
November 2020

A CRISPR-Cas9 repressor for epigenetic silencing of KRAS.

Pharmacol Res 2021 Feb 14;164:105304. Epub 2020 Nov 14.

Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX, 77204, United States. Electronic address:

KRAS is one of the most frequently mutated oncogenes in cancers. Currently no direct and effective anti-KRAS therapies are available. Using the powerful CRISPR-Cas9 technology to target the mutant KRAS promoter, we designed an epigenetic repressor to silence KRAS through epigenome editing. Catalytically dead Cas9 (dCas9) functioned as a DNA binding device, which was fused with a transcriptional repressor histone deacetylase 1 (HDAC1). We designed a panel of three CRISPR RNAs (crRNAs) covering 1500-bp range of the KRAS promoter and identified that crRNA1 and crRNA2 efficiently silenced KRAS. The suppression of K-Ras resulted in a significant inhibition of cell growth, suppression of colony formation in soft agar and induction of cell death in cancer cells with KRAS mutations. In addition, the chromatin immunoprecipitation (ChIP) assay demonstrated dCas9-HDAC1 modified histone acetylation on the KRAS promoter. Furthermore, transfection of dCas9-HDAC1 protein and gRNA ribonucleoprotein complex also inhibited K-Ras and suppressed cell proliferation. In summary, we have developed a new strategy that combines CRISPR-Cas9 technology with HDAC1 epigenetic silencing to target cancers driven by KRAS mutations.
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http://dx.doi.org/10.1016/j.phrs.2020.105304DOI Listing
February 2021

Virtual Reality Exposure Therapy (VRET) for Anxiety Due to Fear of COVID-19 Infection: A Case Series.

Neuropsychiatr Dis Treat 2020 6;16:2669-2675. Epub 2020 Nov 6.

Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong-Macao Greater Bay Area, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Virtual reality exposure therapy (VRET) is becoming popular for treating phobia and anxiety disorder. The recent pandemic of COVID-19 not only causes infection per se but also has an impact on mental health. This case series aimed to explore the role of VRET in the intervention of psychiatric illnesses with chief complaints of fear of COVID-19 infection. In vivo exposure therapy for fear of COVID-19 infection is not possible due to the risk of virus infection; in this scenario, the VRET provides an immersive experience and can act as adjunctive therapy for treating phobias and anxiety disorders arising due to novel coronavirus pandemic. Clinical presentation and findings as well as management and procedures of VRET are discussed. Medical record of three patients (two male and one female) at the Shenzhen Mental Health Center (Shenzhen Kangning Hospital), China, was included in the present case series. Patients were assessed with the Hamilton Anxiety Rating Scale and Fear of COVID-19 Scale to measure anxiety and fear, respectively. Throughout VRET sessions, we gradually and systematically exposed the patient to virtual COVID-19 scenarios (for example, touching stained door handle which may have viruses, watching pandemic news, watching frontline health care workers, etc.). In our study, VRET intervention significantly reduced the related symptoms caused by fear of COVID-19 infection. Furthermore, virtual reality can provide relevant theoretical and practical support for exploring the remote psychological counseling of patients in isolation wards.
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http://dx.doi.org/10.2147/NDT.S276203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654305PMC
November 2020

Current Prevention of COVID-19: Natural Products and Herbal Medicine.

Front Pharmacol 2020 16;11:588508. Epub 2020 Oct 16.

Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.

Starting from December 2019, novel coronavirus disease 2019 (COVID-19) pandemic has caused tremendous economic loss and unprecedented health crisis across the globe. While the development of cure is at full speed, less attention and fewer effort have been spent on the prevention of this rapidly spreading respiratory infectious disease. Although so far, several vaccine candidates have advanced into clinical trials, limited data have been released regarding the vaccine efficacy and safety in human, not mention the long-term effectiveness of those vaccines remain as open question yet. Natural products and herbal medicines have been historically used for acute respiratory infection and generally show acceptable toxicity. The favorable stability for oral formulation and ease of scaling up manufacture make it ideal candidate for prophylactic. Hereby, we summarized the most recent advance in SARS-CoV-2 prevention including vaccine development as well as experimental prophylactics. Mainly, we reviewed the natural products showing inhibitory effect on human coronavirus, and discussed the herbal medicines lately used for COVID-19, especially focused on the herbal products already approved by regulatory agency with identifiable patent number. We demonstrated that to fill in the response gap between appropriate treatment and commercially available vaccine, repurposing natural products and herbal medicines as prophylactic will be a vigorous approach to stop or at least slow down SARS-CoV-2 transmission. In the interest of public health, this will lend health officials better control on the current pandemic.
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http://dx.doi.org/10.3389/fphar.2020.588508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597394PMC
October 2020