Publications by authors named "Hai Huang"

685 Publications

Costunolide suppresses melanoma growth via the AKT/mTOR pathway and .

Am J Cancer Res 2021 15;11(4):1410-1427. Epub 2021 Apr 15.

Department of Animal Science and Biotechnology, Kyungpook National University Sangju-si, Gyeongsang buk-do 37224, Republic of Korea.

Melanoma is the most common type of skin cancer and its incidence is rapidly increasing. AKT, and its related signaling pathways, are highly activated in many cancers including lung, colon, and esophageal cancers. Costunolide (CTD) is a sesquiterpene lactone that has been reported to possess neuroprotective, anti-inflammatory, and anti-cancer properties. However, the target and mechanism underlying its efficacy in melanoma have not been identified. In this study, we elucidated the mechanism behind the anti-cancer effect of CTD in melanoma and by identifying CTD as an AKT inhibitor. We first verified that p-AKT and AKT are highly expressed in melanoma patient tissues and cell lines. CTD significantly inhibited the proliferation, migration, and invasion of melanoma cells including SK-MEL-5, SK-MEL-28, and A375 that are overexpressed p-AKT and AKT proteins. We investigated the mechanism of CTD using a computational docking modeling, pull-down, and site directed mutagenesis assay. CTD directly bound to AKT thereby arresting cell cycle at the G1 phase, and inducing the apoptosis of melanoma cells. In addition, CTD regulated the G1 phase and apoptosis biomarkers, and inhibited the expression of AKT/mTOR/GSK3b/p70S6K/4EBP cascade proteins. After reducing AKT expression in melanoma cells, cell growth was significantly decreased and CTD did not showed further inhibitory effects. Furthermore, CTD administration suppressed tumor growth and weight in cell-derived xenograft mice models without body weight loss and inhibited the expression of Ki-67, p-AKT, and p70S6K in tumor tissues. In summary, our study implied that CTD inhibited melanoma progression and . In this study, we reported that CTD could affect melanoma growth by targeting AKT. Therefore, CTD has considerable potential as a drug for melanoma therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085867PMC
April 2021

Rhein Suppresses Colorectal Cancer Cell Growth by Inhibiting the mTOR Pathway In Vitro and In Vivo.

Cancers (Basel) 2021 Apr 30;13(9). Epub 2021 Apr 30.

Department of Animal Science and Biotechnology, ITRD, Kyungpook National University, Sangju 37224, Korea.

Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. Rhein has demonstrated therapeutic effects in various cancer models. However, its effects and underlying mechanisms of action in CRC remain poorly understood. We investigated the potential anticancer activity and underlying mechanisms of rhein in CRC in vitro and in vivo. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of rhein on CRC cells. Wound-healing and Transwell assays were conducted to assess cell migration and invasion capacity. Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. A tissue microarray was used to detect mTOR expression in CRC patient tissues. Gene overexpression and knockdown were done to analyze the function of mTOR in CRC. The anticancer effect of rhein in vivo was assessed in a CRC xenograft mouse model. The results show that rhein significantly inhibited CRC cell growth by inducing S-phase cell cycle arrest and apoptosis. Rhein inhibited CRC cell migration and invasion through the epithelial-mesenchymal transition (EMT) process. mTOR was highly expressed in CRC cancer tissues and cells. Overexpression of mTOR promoted cell growth, migration, and invasion, whereas mTOR knockdown diminished these phenomena in CRC cells in vitro. In addition, rhein directly targeted mTOR and inhibited the mTOR signaling pathway in CRC cells. Rhein promoted mTOR degradation through the ubiquitin-proteasome pathway. Intraperitoneal administration of rhein inhibited HCT116 xenograft tumor growth through the mTOR pathway. In conclusion, rhein exerts anticancer activity in vitro and in vivo by targeting mTOR and inhibiting the mTOR signaling pathway in CRC. Our results indicate that rhein is a potent anticancer agent that may be useful for the prevention and treatment of CRC.
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http://dx.doi.org/10.3390/cancers13092176DOI Listing
April 2021

Creating RNA Specific C-to-U Editase from APOBEC3A by Separation of Its Activities on DNA and RNA Substrates.

ACS Synth Biol 2021 May 2. Epub 2021 May 2.

Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, 200032, China.

APOBEC3A (A3A) is a cytidine deaminase involved in innate immune response and is able to catalyze deamination on both DNA and RNA substrates. It was used in creating the CRISPR-mediated base editor, but has since been held back due to its dual activities. On the other hand, it has been a challenge to separate A3A's dual activities in order to enable it for single-base RNA editors. Here we developed the reporter system for C-to-U RNA editing and employed rational design for mutagenesis to differentiate deaminase activities on RNA and DNA substrates to obtain an RNA-specific editase. Generation and examination of 23 previous A3A mutants showed their deamination activity on RNA was mostly abolished when their activity on DNA was impaired, with the exception of mutant N57Q that displayed an inverse change. We designed new mutations on Loops 1 and 7 based on A3A's crystal structure and found mutants H29R and Y132G had differential effects on catalytic activity on RNA and DNA substrates. In order to engineer an A3A with RNA-specific deaminase activity, we combined Y132G with mutations in Loop 1 or helix 6 by rational design. Two multipoint mutants, Y132G/K30R and Y132G/G188A/R189A/L190A, were successful in retaining high deaminase activity on RNA substrate while eliminating deaminase activity on DNA. We, for the first time, created novel human A3A variants with RNA-specific cytidine deaminase activity, providing insight into A3A's mechanism on substrate recognition and a new addition of a toolset to the creation of a RNA-specific C-to-U base editor.
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http://dx.doi.org/10.1021/acssynbio.0c00627DOI Listing
May 2021

Identification and Functional Analysis of a Lysozyme Gene from (Hemiptera: Dinidoridae).

Biology (Basel) 2021 Apr 14;10(4). Epub 2021 Apr 14.

Guizhou Provincial Key Laboratory for Agricultural Pest Management of Mountainous Regions, Institute of Entomology, Guizhou University, Guiyang 550025, China.

is a valuable medicinal insect resource in China. Previous studies have indicated that the antibacterial and anticancer effects of the extract mainly come from the active polypeptides. Lysozyme is an effective immune effector in insect innate immunity and usually has excellent bactericidal effects. There are two kinds of lysozymes in insects, c-type and i-type, which play an important role in innate immunity and intestinal digestion. Studying lysozyme in will be helpful to further explore the evolutionary relationship and functional differences among lysozymes of various species and to determine whether they have biological activity and medicinal value. In this study, a lysozyme CcLys2 was identified from . CcLys2 contains 223 amino acid residues, and possesses a typical domain of the c-type lysozyme and a putative catalytic site formed by two conserved residues Glu32 and Asp50. Phylogenetic analysis showed that CcLys2 belongs to the H-branch of the c-type lysozyme. The analysis of spatiotemporal expression patterns indicated that was mainly expressed in the fat body of adults and was highly expressed in the second- and fifth-instar nymphs. In addition, was significantly up-regulated after injecting and feeding bacteria. In the bacterial inhibition assay, it was found that CcLys2 had antibacterial activity against Gram-positive bacteria at a low pH. These results indicate that CcLys2 has muramidase activity, involves in the innate immunity of and is also closely related to the bacterial immune defense or digestive function of the intestine.
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http://dx.doi.org/10.3390/biology10040330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071013PMC
April 2021

Comparison of Gonadal Transcriptomes Uncovers Reproduction-Related Genes with Sexually Dimorphic Expression Patterns in .

Animals (Basel) 2021 Apr 7;11(4). Epub 2021 Apr 7.

Guangdong Research Center on Reproductive Control and Breeding Technology of Indigenous Valuable Fish Species, Key Laboratory of Marine Ecology and Aquaculture Environment of Zhanjiang, Fisheries College, Guangdong Ocean University, Zhanjiang 524088, China.

is a new and emerging aquaculture species in south China. However, due to the lack of understanding of reproductive regulation, the management of breeding and reproduction under captivity remains a barrier for the commercial aquaculture of . More genetic information is needed to identify genes critical for gonadal development. Here, the first gonadal transcriptomes of were analyzed and 151.89 million clean reads were generated. All reads were assembled into 57,077 unigenes, and 24,574 could be annotated. By comparing the gonad transcriptomes, 11,487 differentially expressed genes were obtained, of which 4599 were upregulated and 6888 were downregulated in the ovaries. Using enrichment analyses, many functional pathways were found to be associated with reproduction regulation. A set of sex-biased genes putatively involved in gonad development and gametogenesis were identified and their sexually dimorphic expression patterns were characterized. The detailed transcriptomic data provide a useful resource for further research on reproductive manipulation.
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http://dx.doi.org/10.3390/ani11041042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068034PMC
April 2021

Reactive oxygen species and glutathione dual responsive nanoparticles for enhanced prostate cancer therapy.

Mater Sci Eng C Mater Biol Appl 2021 Apr 11;123:111956. Epub 2021 Feb 11.

Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. Electronic address:

Docetaxel (DTX)-based chemotherapy of prostate cancer is still confronted with significant challenges due to insufficient drug accumulation at the tumor sites and the systemic side effects on normal cells and organs. Tumor microenvironment-responsive nanosized drug delivery systems have shown enormous potential to improve the anticancer efficacy and minimize the systemic side effects of chemotherapeutics. However, most of the currently redox-responsive nanoparticles respond only to single stimuli, which compromise the treatment effect. Hence, inspired by the abundance of reactive oxygen species (ROS) and intracellular glutathione (GSH) in cancer cells, we proposed a unique ROS and GSH dual responsive nanocarrier (PCL-SS) for DTX delivery. The DTX-loaded PCL-SS nanoparticles (PCL-SS@DTX NPs) were not only stable in a normal physiological environment but also rapidly triggered DTX release in prostate cancer cells. In vitro experiments showed that PCL-SS@DTX NPs had robust prostate cancer cell cytotoxicity, induced cell apoptosis, inhibited cell migration and invasion and exhibited satisfactory biocompatibility. In mice bearing orthotopic prostate cancer, PCL-SS@DTX NPs could accumulate in orthotopic tumor sites and then significantly weaken tumor growth by inhibiting prostate cancer cell proliferation and inducing cell apoptosis, without obvious damages to major organs. Overall, this dual responsive nanosized drug delivery system may act as a promising therapeutic option for prostate cancer chemotherapy.
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http://dx.doi.org/10.1016/j.msec.2021.111956DOI Listing
April 2021

Estimation of the Vehicle Speed Using Cross-Correlation Algorithms and MEMS Wireless Sensors.

Sensors (Basel) 2021 Mar 2;21(5). Epub 2021 Mar 2.

Department of Civil and Environmental Engineering, Virginia Tech University, Blacksburg, VA 24060, USA.

Traffic information is critical for pavement design, management, and health monitoring. Numerous in-pavement sensors have been developed and installed to collect the traffic volume and loading amplitude. However, limited attention has been paid to the algorithm of vehicle speed estimation. This research focuses on the estimation of the vehicle speed based on a cross-correlation method. A novel wireless micro-electromechanical sensor (MEMS), Smartrock is used to capture the triaxial acceleration, rotation, and stress data. The cross-correlation algorithms, i.e., normalized cross-correlation (NCC) algorithm, the smoothed coherence transform (SCOT) algorithm, and the phase transform (PHAT) algorithm, are applied to estimate the loading speed of an accelerated pavement test (APT) and the traffic speed in the field. The signal-noise-ratio (SNR) and the mean relative error (MRE) are utilized to evaluate the stability and accuracy of the algorithms. The results show that both the correlated noise and independent noise have significant influence in the field data. The SCOT algorithm is recommended for speed estimation with reasonable accuracy and stability because of a large SNR value and the lowest MRE value among the algorithms. The loading speed investigated in this study was within 50 km/h and further verification is needed for higher speed estimation.
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http://dx.doi.org/10.3390/s21051721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958638PMC
March 2021

Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo.

J Exp Clin Cancer Res 2021 Mar 30;40(1):114. Epub 2021 Mar 30.

Department of Animal Science and Biotechnology, ITRD, Kyungpook National University, Sangju, 37224, Republic of Korea.

Background: Colorectal cancer (CRC) is a clinically challenging malignant tumor worldwide. As a natural product and sesquiterpene lactone, Costunolide (CTD) has been reported to possess anticancer activities. However, the regulation mechanism and precise target of this substance remain undiscovered in CRC. In this study, we found that CTD inhibited CRC cell proliferation in vitro and in vivo by targeting AKT.

Methods: Effects of CTD on colon cancer cell growth in vitro were evaluated in cell proliferation assays, migration and invasion, propidium iodide, and annexin V-staining analyses. Targets of CTD were identified utilizing phosphoprotein-specific antibody array; Costunolide-sepharose conjugated bead pull-down analysis and knockdown techniques. We investigated the underlying mechanisms of CTD by ubiquitination, immunofluorescence staining, and western blot assays. Cell-derived tumour xenografts (CDX) in nude mice and immunohistochemistry were used to assess anti-tumour effects of CTD in vivo.

Results: CTD suppressed the proliferation, anchorage-independent colony growth and epithelial-mesenchymal transformation (EMT) of CRC cells including HCT-15, HCT-116 and DLD1. Besides, the CTD also triggered cell apoptosis and cell cycle arrest at the G2/M phase. The CTD activates and induces p53 stability by inhibiting MDM2 ubiquitination via the suppression of AKT's phosphorylation in vitro. The CTD suppresses cell growth in a p53-independent fashion manner; p53 activation may contribute to the anticancer activity of CTD via target AKT. Finally, the CTD decreased the volume of CDX tumors without of the body weight loss and reduced the expression of AKT-MDM2-p53 signaling pathway in xenograft tumors.

Conclusions: Our project has uncovered the mechanism underlying the biological activity of CTD in colon cancer and confirmed the AKT is a directly target of CTD. All of which These results revealed that CTD might be a new AKT inhibitor in colon cancer treatment, and CTD is worthy of further exploration in preclinical and clinical trials.
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http://dx.doi.org/10.1186/s13046-021-01895-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010944PMC
March 2021

Finite Element Analysis of Femoral Neck Fracture Treated with Bidirectional Compression-Limited Sliding Screw.

Med Sci Monit 2021 Mar 30;27:e929163. Epub 2021 Mar 30.

Department of Anatomy, School of Basic Medical Science, Southern Medical University and Guangdong Provincial Key Laboratory of Medical Biomechanics and Academy of Orthopedics of Guangdong Province, Guangzhou, Guangdong, China (mainland).

BACKGROUND The rate of femoral neck shortening after internal fixation for femoral neck fracture is high and this complication reduces the function of the affected lower limb. The aim of this study was to design a bidirectional compression-limited sliding screw (BCLSC) that can achieve a full balance between retaining the sliding pressure of the ends of and maintaining the length of the femoral neck. MATERIAL AND METHODS We constructed a 3-dimensional model of a Pauwels III femoral neck fracture and models of 3 internal fixation methods (3 cannulated screws [3CS], dynamic hip screw [DHS]+CS, and BCLSC) by finite element analysis (FEA).The finite element model simulated the loading of the human body when standing on 1 leg. Displacement and stress distribution of the models were calculated based on an axial stress of 600 N. RESULTS The peak von Mises stress (VMS) values of fracture ends in the 3CS, DHS+CS and BCLSC groups were 94.687 MPa, 26.375 MPa and 45.698 MPa; the peak VMS values of internal fixed stress were 451.53 MPa, 174.45 MPa, and 337.34 MPa; the peak VMS values of the lateral femoral wall were 70.021 MPa, 53.033 MPa, and 20.009 MPa; maximum displacements of the femoral head were 1.4482 mm, 1.3813 mm, and 1.3889 mm; and the internal fixed displacement peaks were 4.1134 mm, 3.91 mm, and 4.1004 mm, respectively. CONCLUSIONS The FEA showed that compared with the CS, the new BCLSC showed better performance in resisting shearing force for Pauwels III femoral neck fracture, with better mechanical properties. These data provide a basis for further experiments and clinical application.
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http://dx.doi.org/10.12659/MSM.929163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019266PMC
March 2021

Ru-Catalyzed [3 + 2] Cycloaddition of Nitrile Oxides and Electron-Rich Alkynes with Reversed Regioselectivity.

Org Lett 2021 Apr 22;23(7):2431-2436. Epub 2021 Mar 22.

Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China.

Polarity reversal ("umpolung") of a functional group can override its inherent reactivity and lead to distinct bond-forming modes. Herein we describe a rarely studied cycloaddition between nitrile oxides and electron-rich alkynes with reversed regioselectivity, leading to the useful 4-heterosubstituted isoxazoles. The use of a ruthenium catalyst completely overrides the inherent polarity of nitrile oxides. This reversed regioselectivity was also observed for their reactions with a range of electron-deficient alkynes.
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http://dx.doi.org/10.1021/acs.orglett.1c00273DOI Listing
April 2021

Symptomatic features and prognosis of 932 hospitalized patients with coronavirus disease 2019 in Wuhan.

J Dig Dis 2021 Mar 20. Epub 2021 Mar 20.

Optical Valley Branch of Maternal and Child Hospital of Hubei Province, Wuhan, Hubei Province, China.

Objective: To discern the symptomatic features of coronavirus disease 2019 (COVID-19) and to evaluate the severity and prognosis of the disease.

Methods: In this retrospective cohort study, 932 hospitalized patients with COVID-19 in Wuhan were enrolled, including 52 severe and 880 non-severe cases. All patients were followed up for 3 months after discharge. The symptomatic features and follow-up data of the patients in both groups were analyzed and compared.

Results: Of the 932 patients, fever (60.0%), cough (50.8%) and fatigue (36.4%) were the most common symptoms. In total, 32.7% of the severe cases presented with gastrointestinal symptoms at disease onset, including anorexia, nausea, vomiting or diarrhea, which was significantly higher than that of the non-severe group (P = 0.0015). The incidence of olfactory disturbance and dysgeusia was only 3.1% and 6.2%, respectively. After adjusting for age and sex, multivariate regression analysis showed that fever lasting for over 5 days (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.00-3.62, P = 0.0498), anorexia at onset (OR 2.61, 95% CI 1.26-5.40, P = 0.0096), and modified Medical Research Council level above grade 2 when dyspnea occurred (OR 14.19, 95% CI 7.01-28.71, P < 0.0001) were symptomatic risk factors for severe COVID-19. During the follow-up, cough (6.2%), dyspnea (7.2%), fatigue (1.8%), olfactory disturbance and dysgeusia (1.5%) were the significant remaining symptoms.

Conclusions: COVID-19 causes clusters of symptoms with multiple systems involved. Certain symptomatic characteristics have predictive value for severe COVID-19. Short-term follow-up data reveal that most patients have a good prognosis.
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http://dx.doi.org/10.1111/1751-2980.12983DOI Listing
March 2021

Cytonemes with complex geometries and composition extend into invaginations of target cells.

J Cell Biol 2021 May;220(5)

Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA.

Cytonemes are specialized filopodia that mediate paracrine signaling in Drosophila and other animals. Studies using fluorescence confocal microscopy (CM) established their general paths, cell targets, and essential roles in signaling. To investigate details unresolvable by CM, we used high-pressure freezing and EM to visualize cytoneme structures, paths, contents, and contacts. We observed cytonemes previously seen by CM in the Drosophila wing imaginal disc system, including disc, tracheal air sac primordium (ASP), and myoblast cytonemes, and identified cytonemes extending into invaginations of target cells, and cytonemes connecting ASP cells and connecting myoblasts. Diameters of cytoneme shafts vary between repeating wide (206 ± 51.8 nm) and thin (55.9 ± 16.2 nm) segments. Actin, ribosomes, and membranous compartments are present throughout; rough ER and mitochondria are in wider proximal sections. These results reveal novel structural features of filopodia and provide a basis for understanding cytoneme cell biology and function.
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http://dx.doi.org/10.1083/jcb.202101116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980254PMC
May 2021

Dual pH- and Glutathione-Responsive CO-Generating Nanodrug Delivery System for Contrast-Enhanced Ultrasonography and Therapy of Prostate Cancer.

ACS Appl Mater Interfaces 2021 Mar 15;13(11):12899-12911. Epub 2021 Mar 15.

Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.

Ultrasonography (US) contrast imaging using US contrast agents has been widely applied for the diagnosis and differential diagnosis of tumors. Commercial US contrast agents have limited applications because of their large size and shorter imaging time. At the same time, the desired therapeutic purpose cannot be achieved by applying only conventional US contrast agents. The development of nanoscale US agents with US imaging and therapeutic functions has attracted increasing attention. In this study, we successfully developed DOX-loaded poly-1,6-hexanedithiol-sodium bicarbonate nanoparticles (DOX@HADT-SS-NaHCO NPs) with pH-responsive NaHCO and GSH-responsive disulfide linkages. DOX@HADT-SS-NaHCO NPs underwent acid-triggered decomposition of NaHCO to generate CO bubbles and a reduction of disulfide linkages to further promote the release of CO and DOX. The potential of DOX@HADT-SS-NaHCO NPs for contrast-enhanced US imaging and therapy of prostate cancer was thoroughly evaluated using in vitro agarose gel phantoms and a C4-2 tumor-bearing nude mice model. These polymeric NPs displayed significantly enhanced US contrast at acidic pH and antitumor efficacy. Therefore, the NaHCO and DOX-encapsulated polymeric NPs hold tremendous potential for effective US imaging and therapy of prostate cancer.
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http://dx.doi.org/10.1021/acsami.1c00077DOI Listing
March 2021

A reassessment of several erstwhile methods for isolating DNA fragments from agarose gels.

3 Biotech 2021 Mar 23;11(3):138. Epub 2021 Feb 23.

Key Lab of Endemic and Ethnic Diseases of the Ministry of Education of China in Guizhou Medical University, Guiyang, 550004 Guizhou People's Republic of China.

Molecular biology research often requires extraction of DNA fragments from agarose gels. In the past decades, there have been many methods developed for this purpose. Currently most researchers, especially novices, use commercial kits for this extraction, although these kits cost money and the procedures involved are not necessarily easier than some erstwhile methods. We herein reintroduce and reassess several simple and cost-free older methods. One method involves excising a slice of the gel containing the DNA fragment, followed by a thaw-and-freeze procedure to release the DNA from the gel slice into the gel-making buffer. The second method involves a dialysis tubing and requires electroelution of the DNA from the gel slice in the tubing. The third one is to centrifuge the gel slice to release the DNA. The fourth method requires electro-transfer of the DNA from the gel into a filter paper, while the fifth one includes either allowing the DNA in the slice to be dissolved into a buffer or dissolving the DNA-containing gel slice, followed by DNA precipitation with ethanol or isopropanol. The strengths and weaknesses of these methods are discussed to assist researchers in making their choice. We also point out that some of the end uses of the DNA fragment in the agarose gel may not actually require extraction of the DNA. For instance, a tiny DNA-containing gel block or filter paper can be directly used as the template in a nested or semi-nested polymerase chain reaction to preliminarily determine the identity of the DNA fragment.
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http://dx.doi.org/10.1007/s13205-021-02691-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902746PMC
March 2021

Platelet TLR4-ERK5 Axis Facilitates NET-Mediated Capturing of Circulating Tumor Cells and Distant Metastasis after Surgical Stress.

Cancer Res 2021 Mar 9. Epub 2021 Mar 9.

Department of Surgery, The Ohio State University Medical Center, Columbus, Ohio.

Surgical removal of malignant tumors is a mainstay in controlling most solid cancers. However, surgical insult also increases the risk of tumor recurrence and metastasis. Tissue trauma activates the innate immune system locally and systemically, mounting an inflammatory response. Platelets and neutrophils are two crucial players in the early innate immune response that heals tissues, but their actions may also contribute to cancer cell dissemination and distant metastasis. Here we report that surgical stress-activated platelets enhance the formation of platelet-tumor cell aggregates, facilitating their entrapment by neutrophil extracellular traps (NET) and subsequent distant metastasis. A murine hepatic ischemia/reperfusion (I/R) injury model of localized surgical stress showed that I/R promotes capturing of aggregated circulating tumor cells (CTC) by NETs and eventual metastasis to the lungs, which are abrogated when platelets are depleted. Hepatic I/R also increased deposition of NETs within the lung microvasculature, but depletion of platelets had no effect. TLR4 was essential for platelet activation and platelet-tumor cell aggregate formation in an ERK5-GPIIb/IIIa integrin-dependent manner. Such aggregation facilitated NET-mediated capture of CTCs under static and dynamic conditions. Blocking platelet activation or knocking out TLR4 protected mice from hepatic I/R-induced metastasis with no CTC entrapment by NETs. These results uncover a novel mechanism where platelets and neutrophils contribute to metastasis in the setting of acute inflammation. Targeted disruption of the interaction between platelets and NETs holds therapeutic promise to prevent postoperative distant metastasis. SIGNIFICANCE: Targeting platelet activation via TLR4/ERK5/integrin GPIIb/IIIa signaling shows potential for preventing NET-driven distant metastasis in patients post-resection.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3222DOI Listing
March 2021

Particle Size Effect and Temperature Effect on the Pore Structure of Low-Rank Coal.

ACS Omega 2021 Mar 19;6(8):5865-5877. Epub 2021 Feb 19.

College of Petroleum Engineering, Xi'an Shiyou University, Xi'an 710065, China.

High moisture content and high volatile content are typical characteristics of low-rank coal. To acquire the pore structure characteristics of low-rank coal accurately, the particle sizes and the pretreatment temperatures are two key parameters that should be considered when the low-pressure liquid-nitrogen adsorption is used. In this study, a low-rank coal sample was collected from Ordos Basin, and it was polished into four different particle sizes, 40-80 mesh, 80-120 mesh, 120-160 mesh, and 160-200 mesh, respectively. Besides, the low-rank coal samples are handled under seven various pretreatment temperatures (ranging from 120 to 300 °C); then, the pore structure characteristics of low-rank coal under various particle sizes and pretreatment temperatures are acquired. The dynamic change of pore volume and pore-specific surface area for low-rank coal is coincident. Under the same pretreatment temperatures, the mesopores' volume continuously decreases. When the pretreatment temperature reaches 300 °C, a faint increase in their volume is observed. These results mean the mesopores are damaged during the progressive pulverization and heating procedures. When it comes to the same particle sizes, the mesopores' volume also decreased with the increased pretreatment temperatures. Contrarily, the macropore volume is stable. This is mainly due to the decomposition of volatile matters and collapse of mesopores under the high pretreatment temperatures. However, the enrichment of ash in the mesopores could maintain the coal skeleton. The particle size effect and temperature effect mainly relate to the mesopores in low-rank coal, and the pores with the aperture below 5 nm contribute predominantly, followed by the pores with the aperture ranging from 5 to 10 nm.
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http://dx.doi.org/10.1021/acsomega.0c06280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931389PMC
March 2021

Clinical Utility of F-PSMA-1007 Positron Emission Tomography/Magnetic Resonance Imaging in Prostate Cancer: A Single-Center Experience.

Front Oncol 2020 11;10:612701. Epub 2021 Feb 11.

Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Purpose: This study aimed to evaluate the clinical utility of F-PSMA-1007 positron emission tomography (PSMA PET)/magnetic resonance imaging (MRI) imaging in patients with suspected or defined prostate cancer.

Methods: In the pilot study, we retrospectively investigated 62 patients who underwent PSMA-PET/MRI for suspected or defined PCa between June 2019 and June 2020. Patients were grouped into three subgroups: (1) suspected PCa without histological evidence, (2) primary PCa, (3) biochemical recurrent prostate cancer (BRPCa). Two nuclear physicians independently interpreted the results of PSMA-PET/MRI. Management strategies before PSMA-PET/MRI were retrospectively reported, and the management strategy was re-evaluated for each patient considering the PSMA-PET/MRI result. The changes in strategies were recorded. Besides, the correlation between prostate specific antigen (PSA) level and management changes was also accessed by Fisher exact test, and two-side p < 0.05 was assumed as statistical significance.

Results: There were 28 patients in the suspected PCa group (group 1), 12 in the primary PCa group (group 2), and 22 in the BRPCa group (group 3). Overall, the intended decisions were changed in 26 (41.9%) of 62 patients after PSMA-PET/MRI, including 11/28 (39.3%) in suspected PCa group, 1/12 (8.4%) in primary PCa group, and 14/24 (63.6%) in BCR group. In group 1, the main impact on subsequent management included decreased active surveillance (from 20 to 9) and increased prostate biopsy (from 8 to 19). PSA levels were not significantly associated with management changes in suspected PCa patients (p = 0.865). In group 2, the main impact on subsequent management included decreased radical surgery (from 8 to 7), and multimodal therapy appearance (n = 1). Only in the category of PSA levels of ≥20 ng/ml, the management of primary PCa was changed. In group 3, the main impact on subsequent management included decreased salvage radiotherapy (from 5 to 2), increased systemic therapy (from 6 to 7), and increased multimodal therapy (from 11 to 13). The highest proportion of management changes occurred in BCR patients with 0.5≤PSA<1 ng/ml.

Conclusion: From our preliminary experience, PSMA-PET/MRI may be a valued tool for defining PCa lesions and changing management. The biggest impact of management intent was in patients with BRPCa, especially in patients with 0.5≤PSA<1 ng/ml. However, further studies are needed to confirm our pilot findings.
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http://dx.doi.org/10.3389/fonc.2020.612701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928386PMC
February 2021

Anticancer effects and potential mechanisms of ginsenoside Rh2 in various cancer types (Review).

Oncol Rep 2021 04 2;45(4). Epub 2021 Mar 2.

Department of Animal Science and Biotechnology, Institute for Translational Research in Dentistry, Kyungpook National University, Bukgu, Daegu 41566, Republic of Korea.

Ginsenoside Rh2 (G‑Rh2) is a natural bioactive product derived from Meyer (). G‑Rh2 exhibits anticancer activity in various human cancer cell lines both and by modulating several signaling pathways, such as those of PDZ‑binding kinase/T‑LAK cell‑originated protein kinase, phosphatidylinositol 3‑kinase, protein kinase B, mammalian target of rapamycin, epidermal growth factor receptor, p53, and reactive oxygen species. Moreover, G‑Rh2 could effectively reverse drug resistance and enhance therapeutic effects in cancer therapy. This review summarizes the chemical properties, and anticancer activity, and underlying molecular mechanisms of G‑Rh2 to facilitate cancer chemoprevention studies.
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http://dx.doi.org/10.3892/or.2021.7984DOI Listing
April 2021

Oxidative Stress-Induced Hypermethylation of KLF5 Promoter Mediated by DNMT3B Impairs Osteogenesis by Diminishing the Interaction with β-Catenin.

Antioxid Redox Signal 2021 Apr 5. Epub 2021 Apr 5.

Department of Orthopaedics, Medical College of Zhejiang University, Sir Run Run Shaw Hospital, Hangzhou, People's Republic of China.

Emerging evidence suggests that the pathogenesis of osteoporosis, characterized by impaired osteogenesis, is shifting from estrogen centric to oxidative stress. Our previous studies have shown that the zinc-finger transcription factor krüppel-like factor 5 (KLF5) plays a key role in the degeneration of nucleus pulposus and cartilage. However, its role in osteoporosis remains unknown. We aimed to investigate the effect and mechanism of KLF5 on osteogenesis under oxidative stress. First, KLF5 was required for osteogenesis and stimulated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). KLF5 was hypermethylated and downregulated in ovariectomy-induced osteoporosis mice and in BMSCs treated with HO. Interestingly, DNA methyltransferases 3B (DNMT3B) upregulation mediated the hypermethylation of KLF5 induced by oxidative stress, thereby impairing osteogenic differentiation. The inhibition of KLF5 hypermethylation using DNMT3B siRNA or 5-AZA-2-deoxycytidine (5-AZA) protected osteogenic differentiation of BMSCs from oxidative stress. Regarding the downstream mechanism, KLF5 induced β-catenin expression. More importantly, KLF5 promoted the nuclear translocation of β-catenin, which was mediated by the armadillo repeat region of β-catenin. Consistently, oxidative stress-induced KLF5 hypermethylation inhibited osteogenic differentiation by reducing the expression and nuclear translocation of β-catenin. We describe the novel effect and mechanism of KLF5 on osteogenesis under oxidative stress, which is linked to osteoporosis for the first time. Our results suggested that oxidative stress-induced hypermethylation of KLF5 mediated by DNMT3B impairs osteogenesis by diminishing the interaction with β-catenin, which is likely to contribute to osteoporosis. Targeting the hypermethylation of KLF5 might be a new strategy for the treatment of osteoporosis.
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http://dx.doi.org/10.1089/ars.2020.8200DOI Listing
April 2021

Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial.

Signal Transduct Target Ther 2021 02 10;6(1):58. Epub 2021 Feb 10.

Center for Clinical Microbiology, Division of Infection and Immunity, University College London, and UCL Hospitals NIHR Biomedical Research Centre, London, UK.

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 10 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.
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http://dx.doi.org/10.1038/s41392-021-00488-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873662PMC
February 2021

Exploring the pathogenic function of Pantoea ananatis endogenous plasmid by an efficient and simple plasmid elimination strategy.

Microbiol Res 2021 May 28;246:126710. Epub 2021 Jan 28.

College of Plant Protection, Nanjing Agricultural University, Key Laboratory of Monitoring and Management of Crop Disease and Pest Insects, Ministry of Education, Nanjing 210095, China. Electronic address:

The bacterium Pantoea ananatis is associated with devastating plant diseases that cause serious economic losses. Strain DZ-12 was previously isolated from maize brown rot leaves in Hebei Province, China and its genome sequencing revealed that it belongs to P. ananatis. It contains a large, endogenous plasmid, pDZ-12. Different studies have shown that virulence determinants are frequently carried on plasmids. To determine whether pDZ-12 from P. ananatis has any effect on pathogenicity, the plasmid was eliminated by substituting its native replication genes with temperature-sensitive replication genes. The resulting temperature-sensitive plasmid could be cured by growing cells at high temperature (37℃). Loss of pDZ-12 from P. ananatis DZ-12 led to a decreased disease severity in maize plants suggesting that the endogenous plasmid is important for pathogenesis. Loss of pDZ-12 also affected the ability of the bacterium to form biofilms. The study provides the first evidence that the endogenous plasmid of P. ananatis DZ-12 is important for pathogenesis in maize plants and carries genes involved in biofilm formation. This study also presents the first report on curing a plasmid from P. ananatis.
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http://dx.doi.org/10.1016/j.micres.2021.126710DOI Listing
May 2021

The traditional experience strategy (TES) and combined ultrasonography examination (CUE) for the treatment of lateral compression type 1 pelvic fractures: a historical control study.

BMC Musculoskelet Disord 2021 Jan 25;22(1):110. Epub 2021 Jan 25.

Department of Orthopedic Trauma, Honghui Hospital, Xi'an Jiaotong University, Beilin District, No. 555 Youyi East Road, Shaanxi Province, 710054, Xi'an, Republic of China.

Background: It is difficult to judge the stability of lateral compression type-1 (LC-1) pelvic fracture, as it is often based on static images of the pelvis. Compared with the traditional experience strategy, ultrasonography examination may be able to distinguish operative and conservative patients before definitive treatment. However, in previous studies, we have not compared the outcomes between traditional experience strategy (TES group) and combined ultrasonography examination (CUE group). Thus, the aim of the study is comparing the differences between TES and CUE strategy, to identify the value of ultrasonography examination.

Methods: Medical records system for patients with LC-1 pelvic fractures who were treated with TES and CUE strategy were included. Patients' baseline characteristics, treatment strategy, and function were recorded at follow-up. Functional outcomes were evaluated using the Majeed grading system.

Results: In total, 77 patients with LC-1 pelvic fractures were included in the study. There were 42 and 35 patients in TES and CUE group, respectively. Compared to TES group (69 %), there were less proportion patients chosen the operative treatment in CUE group (43 %, P = 0.021). The volume of intraoperative blood loss in CUE operative group was more than TES operative group (P = 0.037). There were more patients with complete sacral fracture in CUE operative group than TES operative group (P = 0.002). The Majeed scores in CUE conservative group was higher than TES conservative group (P = 0.008). The overall Majeed scores in CUE group was higher than that in TES group (P = 0.039).

Conclusions: The ultrasonography examination could relatively accurately identify the unstable LC-1 pelvis than the traditional experience strategy, the operative rate could be reduced and the overall function of LC-1 patients could be improved under the ultrasonography examination.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1186/s12891-021-03993-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836564PMC
January 2021

LC/MS-Based Global Metabolomic Identification of Serum Biomarkers Differentiating Hepatocellular Carcinoma from Chronic Hepatitis B and Liver Cirrhosis.

ACS Omega 2021 Jan 4;6(2):1160-1170. Epub 2021 Jan 4.

Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang 310014, China.

Chronic hepatitis B virus (CHB) infection is one of the primary risk factors associated with the development of hepatocellular carcinoma (HCC). Despite having been extensively studied, diagnosing early-stage HCC remains challenging, and diagnosed patients have a poor (3-5%) survival rate. Identifying new approaches to detect changes in the serum metabolic profiles of patients with CHB and liver cirrhosis (LC) may provide a valuable approach to better detect HCC at an early stage when it is still amenable to treatment, thereby improving patient prognosis and survival. In the present study, we, therefore, employed a liquid chromatography-mass spectrometry (LC-MS)-based approach to evaluate the serum metabolic profiles of 30 CHB patients, 29 LC patients, and 30 HCC patients. We then employed appropriate statistical methods to identify those metabolites that were best able to distinguish HCC cases from LC and CHB controls. A mass-based database was then used to putatively identify these metabolites. We then confirmed the identities of a subset of these metabolites through comparisons with the MS/MS fragmentation patterns and retention times of reference standards. The serum samples were then reanalyzed to quantify the levels of these selected metabolites and of other metabolites that have previously been identified as potential HCC biomarkers. Through this approach, we observed clear differences in the metabolite profiles of the CHB, LC, and HCC patient groups in both positive- and negative-ion modes. We found that the levels of taurodeoxy cholic acid (TCA) and 1,2-diacyl-3-β-d-galactosyl--glycerol rose with the progression from CHB to LC to HCC, whereas levels of 5-hydroxy-6,8,11,14,17-eicosapentaenoic acid, and glycyrrhizic acid were gradually reduced with liver disease progression in these groups. The ROC analysis showed that taurodeoxy cholic acid (TCA), 1,2-diacyl-3-β-d-galactosyl--glycerol, 5-hydroxy-6,8,11,14,17-eicosapentaenoic acid, and glycyrrhizic acid had a diagnosis performance with liver disease progression. These four metabolites have a significant correlation with alpha fetal protein (AFP) level and age. Our results highlight novel metabolic biomarkers that have the potential to be used for differentiating between CHB, LC, and HCC patients, thereby facilitating the identification and treatment of patients with early-stage HCC.
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http://dx.doi.org/10.1021/acsomega.0c04259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818305PMC
January 2021

Mild C-C Bond Formation via Lewis Acid Catalyzed Oxetane Ring Opening with Soft Carbon Nucleophiles.

Angew Chem Int Ed Engl 2021 Feb 1;60(5):2668-2673. Epub 2020 Dec 1.

Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou, China.

Mild oxetane opening by soft carbon nucleophiles has been developed for efficient C-C bond formation. In the presence of LiNTf or TBSNTf as catalyst, silyl ketene acetals were found to be effective nucleophiles to generate a wide range of highly oxygenated molecules, which are key substructure in natural products like polyketides. Furthermore, intramolecular oxetane opening by a styrene-based carbon nucleophile via a Prins-type process was also achieved with Sc(OTf) as catalyst, leading to efficient formation of the useful 2,3-dihydrobenzo[b]oxepine skeleton.
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http://dx.doi.org/10.1002/anie.202013062DOI Listing
February 2021

Deep Vein Thrombosis in the Uninjured Lower Extremity: A Retrospective Study of 1454 Patients With Lower Extremity Fractures.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:1076029620986862

Department of Orthopedic Trauma, Honghui Hospital, 12480Xi'an Jiaotong University, Beilin District, Xi'an, Shaanxi Province, People's Republic of China.

The purpose of this study was to identify patients at higher risk of deep venous thrombosis (DVT) in the uninjured lower extremity both preoperatively and postoperatively in patients with lower extremity fractures. We collected the clinical data of patients with lower extremities fractures who presented at Xi'an Honghui Hospital between 1 July, 2015 and 31 October, 2017. Doppler ultrasonography was used to diagnose the DVT. Patients were examined pre- and postoperatively. The patients were divided into thrombosis group and no thrombosis group according to the preoperative and postoperative ultrasonography results. The thrombosis group was defined as patients with DVT in the uninjured lower extremity and the no thrombosis group was defined as patients without DVT in the uninjured lower extremity. This study enrolled 1454 patients who met the inclusion criteria. The incidence of preoperative DVT in the uninjured lower extremity was 9.63% whereas the postoperative incidence was 20.29%. Age (OR = 0.965, 95 CI%: 0.954-0.977; ≤ 0.001) and female (OR = 0.667, 95% CI: 0.451-0.986, = 0.042) were independent risk factors for preoperative DVT in the uninjured lower extremity. Blood loss (OR = 0.997, 95 CI%: 0.995-1.000; = 0.020), D-dimer level at admission (OR = 0.941, 95 CI%: 0.887-0.999; = 0.045), and postoperative day 5 D-dimer level (OR = 0.889, 95 CI%: 0.819-0.965; = 0.005), were independent risk factors for postoperative DVT in the uninjured lower extremity. For the patients with lower extremity fractures, age and female were associated with the preoperative DVT in the uninjured lower extremity. Blood loss, D-dimer at admission and postoperative day 5 D-dimer were associated with the postoperative DVT in the uninjured lower extremity.
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http://dx.doi.org/10.1177/1076029620986862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802023PMC
January 2021

20(S)-Ginsenoside Rh2 Suppresses Oral Cancer Cell Growth by Inhibiting the Src-Raf-ERK Signaling Pathway.

Anticancer Res 2021 Jan;41(1):227-235

Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Republic of Korea;

Background: 20(S)-Ginsenoside Rh2 (G-Rh2) has demonstrated therapeutic effects in many types of cancers. We aimed to investigate the potential anticancer activity and underlying mechanisms of G-Rh2 in oral cancer cells.

Materials And Methods: The antigrowth effect of G-Rh2 in oral cancer cells was stimulated by cell proliferation, soft agar colony formation, and migration and invasion assay. The cell cycle and apoptosis were detected by flow cytometry. The underlying mechanism of G-Rh2 in oral cancer cells was explored by immunoblotting.

Results: G-Rh2 significantly inhibited oral cancer cell growth by inducing apoptosis and cell cycle G/G-phase arrest. G-Rh2 inhibited oral cancer cell migration and invasion through regulation of epithelial-mesenchymal transition (EMT)-related proteins. G-Rh2 inhibited the Src/Raf/ERK signaling pathway in YD10B and Ca9-22 cells.

Conclusion: G-Rh2 exerted anticancer activity in vitro by inhibiting the Src/Raf/ERK signaling pathway in oral cancer. G-Rh2 is a potential therapeutic drug for oral cancer treatment.
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http://dx.doi.org/10.21873/anticanres.14769DOI Listing
January 2021

Activation of hypoxia-inducible factor 1 (Hif-1) enhanced bactericidal effects of macrophages to Mycobacterium tuberculosis.

Tuberculosis (Edinb) 2021 01 24;126:102044. Epub 2020 Dec 24.

Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China. Electronic address:

Background: Tuberculosis is chronic infection caused by Mycobacterium tuberculosis (M.tb), which infects specifically macrophages. Hif-1, hypoxia-inducible factor-1, was reported to act as master regulator of killing functions in macrophages.

Aim: To investigate whether Hif-1 activation would enhance bactericidal effect of macrophages and anti-tuberculosis effect of chemical reagent.

Methods: Hif-1 and LC3B were detected in tissues from pulmonary tuberculosis. U937, human monocytic leukemia cell line, was stimulated with PMA and differentiated into macrophages. Cells were pretreated with Hif-1 chemical inhibitor YC-1, stimulated with CoCl (Hif-1 activator), to detect LC3B with Western blot and confocal microscopy. Cells were infected with M. tb H37Rv strain, stimulated with CoCl, following rifampine treatment. Expression of autophagy markers was detected using Western blot. IL-6 and TNF-α were detected in cell supernatant with ELISA. Acid-fast staining and CFU assay were performed to evaluate intracellular bacterial load.

Results And Conclusions: Hif-1 and LC3B increased in tissues of pulmonary tuberculosis. Hif-1 activation enhanced autophagy in M. tb infected U937 cells and production of IL-6 and TNF-α. Data from acid-fast staining and CFU indicated that Hif-1 activation enhanced anti-tuberculosis effect of rifampine in macrophages. Conclusively, to activate Hif-1 would strengthen bactericidal effect of macrophages, to further enhance anti-tuberculosis effect of chemical reagent.
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http://dx.doi.org/10.1016/j.tube.2020.102044DOI Listing
January 2021

An Organocatalytic Kinetic Resolution of Aziridines by Thiol Nucleophiles.

Org Lett 2021 Jan 31;23(2):554-558. Epub 2020 Dec 31.

Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China.

We report the first organocatalytic kinetic resolution of unactivated aziridines by sulfur nucleophiles with excellent enantioselectivity. A suitable chiral phosphoric acid was found to catalyze the intermolecular ring opening under mild conditions, furnishing a range of highly enantioenriched β-amino thioethers and aziridines, both of which are useful synthetic building blocks.
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http://dx.doi.org/10.1021/acs.orglett.0c04074DOI Listing
January 2021

Surgical Stress Promotes Tumor Progression: A Focus on the Impact of the Immune Response.

J Clin Med 2020 Dec 18;9(12). Epub 2020 Dec 18.

Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.

Despite advances in systemic therapies, surgery is crucial for the management of solid malignancy. There is increasing evidence suggesting that the body's response to surgical stress resulting from tumor resection has direct effects on tumor cells or can alter the tumor microenvironment. Surgery can lead to the activation of early and key components of the innate and adaptative immune systems. Platelet activation and the subsequent pro-coagulation state can accelerate the growth of micrometastases. Neutrophil extracellular traps (NETs), an extracellular network of DNA released by neutrophils in response to inflammation, promote the adhesion of circulating tumor cells and the growth of existing micrometastatic disease. In addition, the immune response following cancer surgery can modulate the tumor immune microenvironment by promoting an immunosuppressive state leading to impaired recruitment of natural killer (NK) cells and regulatory T cells (Tregs). In this review, we will summarize the current understanding of mechanisms of tumor progression secondary to surgical stress. Furthermore, we will describe emerging and novel peri-operative solutions to decrease pro-tumorigenic effects from surgery.
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http://dx.doi.org/10.3390/jcm9124096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766515PMC
December 2020