Publications by authors named "Zhe Jin"

316 Publications

MiRNA-20b/SUFU/Wnt axis accelerates gastric cancer cell proliferation, migration and EMT.

Heliyon 2021 Apr 12;7(4):e06695. Epub 2021 Apr 12.

Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China.

Previous research has found that miRNA-20b is highly expressed in gastric cancer (GC), however, its function and underlying mechanism are not clear. Wnt signaling pathway, implicated in tumorigeneisis, is activated in more than 30% of GC. We would like to characterize the biological behavior of miRNA-20b in terms of modulating Wnt/β-catenin signaling and EMT. We showed that miRNA-20b inhibitors suppressed Topflash/Fopflash dependent luciferase activity and the β-catenin nuclear translocation, resulting in inhibition of Wnt pathway activity and EMT. SUFU, negatively regulating Wnt and Hedgehog signaling pathway, was proved to be targeted by miRNA-20b. Moreover, additional knockdown of SUFU alleviated the inhibitory effect on Wnt pathway activity, EMT, cell proliferation/migration and colony formation caused by miRNA-20b inhibition. In summary, miRNA-20b is an oncogenic miRNA and promoted cell proliferation, migration and EMT in GC partially by activating Wnt pathway via targeting SUFU.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065298PMC
April 2021

Dual activation of Hedgehog and Wnt/β-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer.

Aging (Albany NY) 2021 Apr 12;13(7):10749-10769. Epub 2021 Apr 12.

Guangdong Key Laboratory for Genome Stability and Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen 518060, Guangdong, P.R. China.

Mounting evidence has shown that miRNA-150 expression is upregulated in gastric cancer (GC) and is associated with gastric carcinogenesis, but the underlying oncogenic mechanism remains elusive. Here, we discovered that miRNA-150 targets the tumor suppressor SUFU to promote cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) via the dual activation of Hedgehog (Hh) and Wnt signaling. MiRNA-150 was highly expressed in GC tissues and cell lines, and the level of this miRNA was negatively related to that of SUFU. In addition, both the miRNA-150 and SUFU levels were associated with tumor differentiation. Furthermore, miRNA-150 activated GC cell proliferation and migration . We found that miRNA-150 inhibitors repressed not only Wnt signaling by promoting cytoplasmic β-catenin localization, but also repressed Hh signaling and EMT. MiRNA-150 inhibition also resulted in significant tumor volume reductions , suggesting the potential application of miRNA-150 inhibitors in GC therapy. The expression of genes downstream of Hh and Wnt signaling was also reduced in tumors treated with miRNA-150 inhibitors. Notably, anti-SUFU siRNAs rescued the inhibitory effects of miRNA-150 inhibitors on Wnt signaling, Hh activation, EMT, cell proliferation, cell migration, and colony formation. Taken together, these findings indicate that miRNA-150 is oncogenic and promotes GC cell proliferation, migration, and EMT by activating Wnt and Hh signaling via the suppression of SUFU expression.
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http://dx.doi.org/10.18632/aging.202895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064165PMC
April 2021

Advances in research on the regulatory mechanism of NHE1 in tumors.

Oncol Lett 2021 Apr 10;21(4):273. Epub 2021 Feb 10.

Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China.

Tumors pose a major threat to human health and present with difficulties that modern medicine has yet to overcome. It has been demonstrated that the acid-base balance of the tumor microenvironment is closely associated with the dynamic balance in the human body and that it regulates several processes, such as cell proliferation and differentiation, intracellular enzyme activity, and cytoskeletal assembly and depolymerization. It has been well established that the regulation of intra- and extracellular pH depends on a series of functional ion transporters and hydrogen ion channels, such as the Na/H exchanger (NHE) protein and thee Cl/HCO- exchange protein, among which the NHE1 member of the NHE family has been attracting increasing attention in recent years, particularly in studies on the correlation between pH regulation and tumors. NHE1 is a housekeeping gene encoding a protein that is widely expressed on the surface of all plasma membranes. Due to its functional domain, which determines the pHi at its N-terminus and C-terminus, NHE1 is involved in the regulation of the cellular pH microenvironment. It has been reported in the literature that NHE1 can regulate cell volume, participate in the transmembrane transport of intracellular and extracellular ions, affect cell proliferation and apoptosis, and regulate cell behavior and cell cycle progression; however, research on the role of NHE1 in tumorigenesis and tumor development in various systems is at its early stages. The aim of the present study was to review the current research on the correlation between the NHE family proteins and various systemic tumors, in order to indicate a new direction for antitumor drug development with the pH microenvironment as the target.
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http://dx.doi.org/10.3892/ol.2021.12534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885159PMC
April 2021

Monoallelic and bi-allelic variants in NCDN cause neurodevelopmental delay, intellectual disability, and epilepsy.

Am J Hum Genet 2021 04 11;108(4):739-748. Epub 2021 Mar 11.

Department of Immunology, Genetics and Pathology, Uppsala University and Science for Life Laboratory, Box 815, 751 08 Uppsala, Sweden. Electronic address:

Neurochondrin (NCDN) is a cytoplasmatic neural protein of importance for neural growth, glutamate receptor (mGluR) signaling, and synaptic plasticity. Conditional loss of Ncdn in mice neural tissue causes depressive-like behaviors, impaired spatial learning, and epileptic seizures. We report on NCDN missense variants in six affected individuals with variable degrees of developmental delay, intellectual disability (ID), and seizures. Three siblings were found homozygous for a NCDN missense variant, whereas another three unrelated individuals carried different de novo missense variants in NCDN. We assayed the missense variants for their capability to rescue impaired neurite formation in human neuroblastoma (SH-SY5Y) cells depleted of NCDN. Overexpression of wild-type NCDN rescued the neurite-phenotype in contrast to expression of NCDN containing the variants of affected individuals. Two missense variants, associated with severe neurodevelopmental features and epilepsy, were unable to restore mGluR5-induced ERK phosphorylation. Electrophysiological analysis of SH-SY5Y cells depleted of NCDN exhibited altered membrane potential and impaired action potentials at repolarization, suggesting NCDN to be required for normal biophysical properties. Using available transcriptome data from human fetal cortex, we show that NCDN is highly expressed in maturing excitatory neurons. In combination, our data provide evidence that bi-allelic and de novo variants in NCDN cause a clinically variable form of neurodevelopmental delay and epilepsy, highlighting a critical role for NCDN in human brain development.
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http://dx.doi.org/10.1016/j.ajhg.2021.02.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059333PMC
April 2021

Concurrent chemoradiotherapy with additional chemotherapy for nasopharyngeal carcinoma: A pooled analysis of propensity score-matching studies.

Head Neck 2021 Feb 28. Epub 2021 Feb 28.

Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.

Objective: To determine the benefits of adding induction chemotherapy (IC) and adjuvant chemotherapy (AC) to concurrent chemoradiotherapy (CCRT) for nasopharyngeal carcinoma (NPC) based on propensity score-matching (PSM) studies.

Methods: Eligible PSM studies were searched in the PubMed, Web of Science, and Embase databases from inception to September 1, 2020. The primary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS).

Results: A total of 14 trials consisting of 4086 participants were included. Significant benefits were observed between IC + CCRT and CCRT for OS (hazard ratio [HR], 0.76; 95% confidence interval [CI]: 0.64-0.91) and DMFS (HR, 0.77; 95% CI: 0.64-0.94) with the exception of LRFS (HR, 1.14; 95% CI: 0.90-1.43). However, CCRT + AC did not achieve significant improvements.

Conclusions: IC with CCRT yields significant survival benefits in terms of OS and DMFS, whereas CCRT with AC fails to achieve any additional benefit in all endpoints.
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http://dx.doi.org/10.1002/hed.26664DOI Listing
February 2021

Fetal cervical zygapophysial joint with special reference to the associated synovial tissue: a histological study using near-term human fetuses.

Anat Cell Biol 2021 Mar;54(1):65-73

Department of Histology and Embryology, Tokyo Dental College, Tokyo, Japan.

Human fetal cervical vertebrae are characterized by the large zygapophysial joint (ZJ) extending posteriorly. During our recent studies on regional differences in the shape, extent, and surrounding tissue of the fetal ZJ, we incidentally found a cervical-specific structure of synovial tissues. This study aimed to provide a detailed evaluation of the synovial structure using sagittal and horizontal sections of 20 near-term fetuses. The cervical ZJ consistently had a large cavity with multiple recesses at the margins and, especially at the anterior end, the recess interdigitated with or were located close to tree-like tributaries of the veins of the external vertebral plexus. In contrast to the flat and thin synovial cell lining of the recess, the venous tributary had cuboidal endothelial cells. No or few elastic fibers were identified around the ZJ. The venous-synovial complex seems to be a transient morphology at and around birth, and it may play a role in the stabilization of the growing cervical ZJ against frequent spontaneous dislocation reported radiologically in infants. The venous-synovial complex in the cervical region should be lost and replaced by elastic fibers in childhood or adolescence. However, the delayed development of the ligament flavum is also likely to occur in the lumbar ZJ in spite of no evidence of a transient venous-synovial structure. The cuboidal venous endothelium may simply represent the high proliferation rate for the growing complex.
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http://dx.doi.org/10.5115/acb.20.265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017452PMC
March 2021

Insulin differentially modulates GABA signalling in hippocampal neurons and, in an age-dependent manner, normalizes GABA-activated currents in the tg-APPSwe mouse model of Alzheimer's disease.

Acta Physiol (Oxf) 2021 Feb 8:e13623. Epub 2021 Feb 8.

Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.

Aim: We examined if tonic γ-aminobutyric acid (GABA)-activated currents in primary hippocampal neurons were modulated by insulin in wild-type and tg-APPSwe mice, an Alzheimer's disease (AD) model.

Methods: GABA-activated currents were recorded in dentate gyrus (DG) granule cells and CA3 pyramidal neurons in hippocampal brain slices, from 8 to 10 weeks old (young) wild-type mice and in dorsal DG granule cells in adult, 5-6 and 10-12 (aged) months old wild-type and tg-APPSwe mice, in the absence or presence of insulin, by whole-cell patch-clamp electrophysiology.

Results: In young mice, insulin (1 nmol/L) enhanced the total spontaneous inhibitory postsynaptic current (sIPSC ) density in both dorsal and ventral DG granule cells. The extrasynaptic current density was only increased by insulin in dorsal CA3 pyramidal neurons. In absence of action potentials, insulin enhanced DG granule cells and dorsal CA3 pyramidal neurons miniature IPSC (mIPSC) frequency, consistent with insulin regulation of presynaptic GABA release. sIPSC densities in DG granule cells were similar in wild-type and tg-APPSwe mice at 5-6 months but significantly decreased in aged tg-APPSwe mice where insulin normalized currents to wild-type levels. The extrasynaptic current density was increased in tg-APPSwe mice relative to wild-type littermates but, only in aged tg-APPSwe mice did insulin decrease and normalize the current.

Conclusion: Insulin effects on GABA signalling in hippocampal neurons are selective while multifaceted and context-based. Not only is the response to insulin related to cell-type, hippocampal axis-location, age of animals and disease but also to the subtype of neuronal inhibition involved, synaptic or extrasynaptic GABA receptors-activated currents.
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http://dx.doi.org/10.1111/apha.13623DOI Listing
February 2021

Predicting hyperprogressive disease in patients with advanced hepatocellular carcinoma treated with anti-programmed cell death 1 therapy.

EClinicalMedicine 2021 Jan 13;31:100673. Epub 2020 Dec 13.

Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.

Background: Hyperprogressive disease (HPD) is a new progressive pattern in patients with advanced hepatocellular carcinoma (HCC) treated with programmed cell death 1 (PD-1) inhibitors. We aimed to investigate risk factors associated with HPD in advanced HCC patients undergoing anti-PD-1 therapy.

Methods: A total of 69 patients treated with anti-PD-1 therapy between March 2017 and January 2020 were included. HPD was determined according to the time to treatment failure, tumour growth rate, and tumour growth rate ratio. Univariate and multivariate analyses were performed to identify clinical variables significantly associated with HPD. A risk model was constructed based on clinical variables with prognostic significance for HPD.

Findings: Overall, 10 (14·49%) had HPD. Haemoglobin level, portal vein tumour thrombus, and Child-Pugh score were significantly associated with HPD. The risk model had an area under the curve of 0·931 (95% confidence interval, 0·844-1·000). Patients with HPD had a significantly shorter overall survival (OS) than that of the patients with non-HPD ( < 0·001). However, there was no significant difference in OS between PD (progressive disease) patients with and without HPD ( = 0·05).

Interpretation: We identified three clinical variables as risk factors for HPD, providing an opportunity to aid the pre-treatment evaluation of the risk of HPD in patients treated with immunotherapy.

Funding: This study was funded by the National Natural Science Foundation of China (81571664, 81871323, and 81801665); National Natural Science Foundation of Guangdong Province (2018B030311024); Scientific Research General Project of Guangzhou Science Technology and Innovation Commission (201707010,328); and China Postdoctoral Science Foundation (2016M600145).
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http://dx.doi.org/10.1016/j.eclinm.2020.100673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846667PMC
January 2021

Massive gastric bleeding - perforation of pancreatic pseudocyst into the stomach: A case report and review of literature.

World J Clin Cases 2021 Jan;9(2):389-395

Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China.

Background: Pancreatic pseudocyst may cause serious gastrointestinal complications including necrosis, infection, and perforation of the gastrointestinal tract wall, but massive gastric bleeding is very rare.

Case: We report a rare case of a 49-year-old man with life-threatening gastric bleeding from a pseudoaneurysm of the splenic artery perforating the stomach induced by pancreatic pseudocyst. During hospitalization, gastroscopy revealed a bare blood vessel in an ulcer-like depression of the greater gastric curvature, and computed tomography scan confirmed a pancreatic pseudocyst invading part of the spleen and gastric wall of the greater curvature. Arteriography showed that the bare blood vessel originated from a pseudoaneurysm of the splenic artery. The bleeding was controlled by the trans-arterial embolization, the patient's recovery was rapid and uneventful.

Conclusion: Massive gastrointestinal bleeding could be a rare complication of pancreatic pseudo aneurysm.
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http://dx.doi.org/10.12998/wjcc.v9.i2.389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812897PMC
January 2021

Whole-Lesion Histogram Analysis of the Apparent Diffusion Coefficient as a Quantitative Imaging Biomarker for Assessing the Level of Tumor-Infiltrating Lymphocytes: Value in Molecular Subtypes of Breast Cancer.

Front Oncol 2020 8;10:611571. Epub 2021 Jan 8.

Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

Purpose: To assess whether apparent diffusion coefficient (ADC) metrics can be used to assess tumor-infiltrating lymphocyte (TIL) levels in breast cancer, particularly in the molecular subtypes of breast cancer.

Methods: In total, 114 patients with breast cancer met the inclusion criteria (mean age: 52 years; range: 29-85 years) and underwent multi-parametric breast magnetic resonance imaging (MRI). The patients were imaged by diffusion-weighted (DW)-MRI (1.5 T) using a single-shot spin-echo echo-planar imaging sequence. Two readers independently drew a region of interest (ROI) on the ADC maps of the whole tumor. The mean ADC and histogram parameters (10, 25, 50, 75, and 90 percentiles of ADC, skewness, entropy, and kurtosis) were used as features to analyze associations with the TIL levels in breast cancer. Additionally, the correlation between the ADC values and Ki-67 expression were analyzed. Continuous variables were compared with Student's t-test or Mann-Whitney U test if the variables were not normally distributed. Categorical variables were compared using Pearson's chi-square test or Fisher's exact test. Associations between TIL levels and imaging features were evaluated by the Mann-Whitney U and Kruskal-Wallis tests.

Results: A statistically significant difference existed in the 10 and 25 percentile ADC values between the low and high TIL groups in breast cancer (=0.012 and 0.027). For the luminal subtype of breast cancer, the 10 percentile ADC value was significantly lower in the low TIL group (=0.041); for the non-luminal subtype of breast cancer, the kurtosis was significantly lower in the low TIL group (=0.023). The Ki-67 index showed statistical significance for evaluating the TIL levels in breast cancer (=0.007). Additionally, the skewness was significantly higher for samples with high Ki-67 levels in breast cancer (=0.029).

Conclusions: Our findings suggest that whole-lesion ADC histogram parameters can be used as surrogate biomarkers to evaluate TIL levels in molecular subtypes of breast cancer.
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http://dx.doi.org/10.3389/fonc.2020.611571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820903PMC
January 2021

Immune-checkpoint inhibitor plus chemotherapy conventional chemotherapy for treatment of recurrent or metastatic head and neck squamous cell carcinoma: a systematic review and network meta-analysis.

Ther Adv Med Oncol 2020 26;12:1758835920983717. Epub 2020 Dec 26.

The First Affiliated Hospital of Jinan University, No. 613, West Huangpu Avenue, Guangzhou, Guangdong Province 510630, PR China.

Background: Multiple therapies including immune-checkpoint inhibitors are emerging as effective treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSSC). However, the optimal first-line and second-line treatments remains controversial.

Methods: We systematically searched databases and conducted a systematic review of phase II/III randomized controlled trials (RCTs) that compared two or more treatments for R/M HNSSC. Progression-free survival (PFS), overall survival (OS) and adverse events (AEs) ⩾3 with hazard ratios (HRs) were extracted and synthesized based on a frequentist network meta-analysis.

Results: Twenty-six trials involving 8908 patients were included. Of first-line treatments, pembrolizumab plus cisplatin plus 5-fluorouracil is associated with significantly improved OS (P-score = 0.91) and TPEx ranked first for prolonging PFS (0.91). EXTREME plus docetaxel (0.18) ranked lowest for AEs ⩾3. Of second-line treatments, nivolumab was the highest-ranked treatment for prolonging OS (0.95), while buparlisib plus paclitaxel was the highest-ranked treatment for PFS (0.94). Subgroup analyses suggested that nivolumab was significantly associated with improvement of OS in patients with high PD-L1 expression (HR 0.55, 0.43-0.70), whereas its OS benefit is similar with conventional chemotherapy for those with low PD-L1 expression. Buparlisib plus paclitaxel showed the best OS benefit in subgroups of patients with HPV-negative status, and with oral cavity or larynx as primary tumor sites.

Conclusions: Pembrolizumab plus cisplatin plus 5-fluorouracil is likely to be the best first-line treatment when OS is a priority. Otherwise, TPEx should be the optimal first-line option due to its superior PFS prolongation efficacy, best safety profile, and similar OS benefit with pembrolizumab plus cisplatin plus 5-fluorouracil. Nivolumab appears to be the best second-line option with best OS prolongation efficacy and outstanding safety profile in the overall population. Future RCTs with meticulous grouping of patients and detailed reporting are urgently needed for individualized treatment.
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http://dx.doi.org/10.1177/1758835920983717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768319PMC
December 2020

Recent advances in small-molecule HIV-1 integrase inhibitors.

Curr Med Chem 2021 Jan 14. Epub 2021 Jan 14.

Key Laboratory of Structure-based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016. China.

HIV-1 integrase catalyzed the insertion of the viral DNA into the genome of human cells in the process of retrotranscription. Integrase is an attractive target for HIV-1 treatment due to the lack of its homologue in human cells and its vital role in HIV-1 replication. Although a major progress about the development of HIV-1 integrase inhibitors has been made, some thorny problems, such as the drug resistance, led to the further study of HIV-1 integrase inhibitors. This review briefly discussed the structure, function and mechanism of catalysis of HIV-1 integrase and made a further conclusion for recent advances in small-molecule inhibitors of HIV-1 integrase.
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http://dx.doi.org/10.2174/0929867328666210114124744DOI Listing
January 2021

Fetal development of the thoracolumbar fascia with special reference to the fascial connection with the transversus abdominis, latissimus dorsi, and serratus posterior inferior muscles.

Surg Radiol Anat 2021 Jan 12. Epub 2021 Jan 12.

Department of Anatomy, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, China.

Purpose: The three-layered thoracolumbar fascia (TLF) encapsulates the erector spinae and the quadratus lumborum and has been a major concern for physical therapists. However, knowledge of its prenatal development and growth is limited.

Methods: Histological examination of 25 embryos and fetuses at 6-37 weeks (CRLs, 15-310 mm).

Results: At the posterior end, the abdominal muscles continued toward an initial posterior layer of the TLF (pTLF) at 6 weeks, but the connection became narrow and limited to the obliquus externus aponeurosis until near term. The middle layer of the TLF (mTLF) appeared as a posterior continuation of the transversalis fascia at 9 weeks and, depending on a mechanical demand for the vertebral column extension near term, it grew as a thick intermuscular septum between the iliocostalis and quadratus lumborum. Thus, the mTLF lateral end changed from the abdominal wall to the back or pTLF. The serratus posterior inferior originated from the pTLF after 9 weeks, but a connection of the latissimus dorsi with the fascia was established much later. Near term, the gluteus maximus was attached to an aponeurosis covering the multifidus behind the sacrum. Therefore, the pTLF extended to cover the gluteal muscles.

Conclusion: We rejected the hypothesis that the mTLF develops as a marginal tissue between the primitive epaxial and hypaxial muscles. This study seemed to be the first report showing a fact that, within prenatal life, a drastic change is likely to occur in interfascial connections and their topographical relation to muscles; the TLF might be the best sample.
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http://dx.doi.org/10.1007/s00276-020-02668-4DOI Listing
January 2021

Variations in Laminar Arrangements of the Mesocolon and Retropancreatic Fascia: a Histological Study Using Human Fetuses Near Term.

Tokai J Exp Clin Med 2020 Dec 20;45(4):214-223. Epub 2020 Dec 20.

Department of Anatomy, Division of Basic Medical Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Objective: The embryonic mesentery of the ascending and descending colons as well as the pancreas disappears due to peritoneal fusion, but there might be no or few photographic demonstrations of the intermediate morphologies during the process. The aims of this study were to characterize the morphological relationship of the interface between the renal fascia and peritoneum.

Methods: Fourteen late-stage fetuses with crown rump lengths (CRLs) of 250-325 mm (gestational age: 30-38 weeks) were histologically examined.

Results: The renal fascia, a thick or thin layer consisting of densely-distributed abundant fibers, was consistently separated from the renal capsule by a perirenal space containing fat. The transverse colon carried a typical mesocolon histologically different from the renal fascia. The ascending and descending mesocolons were irregularly divided into multiple laminae and the colic external longitudinal muscle appeared to directly contact the renal fascia. There was a spectrum of variations from multiple laminae to a single thick fascia between the pancreatic body and the left kidney or adrenal.

Conclusions: A fascial development after retroperitoneal fusion of the mesentery showed great individual and site-dependent differences in proportion of 1) a complete fusion with the renal fascia and 2) a multilaminar structure including the remnant peritoneum. These variations masked the likely stage-dependent change.
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December 2020

Role of gut microbiota via the gut-liver-brain axis in digestive diseases.

World J Gastroenterol 2020 Oct;26(40):6141-6162

Department of Gastroenterology, Affiliated Hospital to Zunyi Medical University, Zunyi 563003, Guizhou Province, China.

The gut-brain axis is a bidirectional information interaction system between the central nervous system (CNS) and the gastrointestinal tract, in which gut microbiota plays a key role. The gut microbiota forms a complex network with the enteric nervous system, the autonomic nervous system, and the neuroendocrine and neuroimmunity of the CNS, which is called the microbiota-gut-brain axis. Due to the close anatomical and functional interaction of the gut-liver axis, the microbiota-gut-liver-brain axis has attracted increased attention in recent years. The microbiota-gut-liver-brain axis mediates the occurrence and development of many diseases, and it offers a direction for the research of disease treatment. In this review, we mainly discuss the role of the gut microbiota in the irritable bowel syndrome, inflammatory bowel disease, functional dyspepsia, non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and hepatic encephalopathy via the gut-liver-brain axis, and the focus is to clarify the potential mechanisms and treatment of digestive diseases based on the further understanding of the microbiota-gut- liver-brain axis.
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http://dx.doi.org/10.3748/wjg.v26.i40.6141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596643PMC
October 2020

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking.

Front Psychiatry 2020 14;11:577155. Epub 2020 Oct 14.

Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, China.

Deep brain stimulation (DBS) modulates the neuronal activity in specific brain circuits and has been recently considered as a promising intervention for refractory addiction. The insula cortex is the hub of interoception and is known to be involved in different aspects of substance use disorder. In the present study, we investigate the effects of continuous high frequency DBS in the anterior insula (AI) on drug-seeking behaviors and examined the molecular mechanisms of DBS action in morphine-addicted rats. Sprague-Dawley rats were trained to the morphine-conditioned place preference (CPP, day 1-8) followed by bilaterally implanted with DBS electrodes in the AI (Day 10) and recovery (Day 10-15). Continuous high-frequency (HF) -DBS (130 Hz, 150 μA, 90 μs) was applied during withdrawal (Day 16-30) or extinction sessions. CPP tests were conducted on days 16, 30, 40 during withdrawal session and several rats were used for proteomic analysis on day 30. Following the complete extinction, morphine-CPP was reinstated by a priming dose of morphine infusion (2 mg/kg). The open field and novel objective recognition tests were also performed to evaluate the DBS side effect on the locomotion and recognition memory. Continuous HF-DBS in the AI attenuated the expression of morphine-CPP post-withdrawal (Day 30), but morphine addictive behavior relapsed 10 days after the cessation of DBS (Day 40). Continuous HF-DBS reduced the period to full extinction of morphine-CPP and blocked morphine priming-induced recurrence of morphine addiction. HF-DBS in the AI had no obvious effect on the locomotor activity and novel objective recognition and did not cause anxiety-like behavior. In addition, our proteomic analysis identified eight morphine-regulated proteins in the AI and their expression levels were reversely changed by HF-DBS. Continuous HF-DBS in the bilateral anterior insula prevents the relapse of morphine place preference after withdrawal, facilitates its extinction, blocks the reinstatement induced by morphine priming and reverses the expression of morphine-regulated proteins. Our findings suggest that manipulation of insular activity by DBS could be a potential intervention to treat substance use disorder, although future research is warranted.
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http://dx.doi.org/10.3389/fpsyt.2020.577155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591677PMC
October 2020

Effects of body weight-supported treadmill training at different speeds on the motor function and depressive behaviors after spinal cord injury in rats.

Neuroreport 2020 12;31(18):1265-1273

Department of Clinical Nursing, School of Nursing, Jilin University, Changchun, Jilin.

Spinal cord injury (SCI) causes motor dysfunction and depression, which hinders the recovery of motor function. Body weight-supported treadmill training (BWSTT) should be considered an effective method for functional rehabilitation after SCI, as it is an efficacious intervention in healthcare with no side effects. Because exercise exerts different effects on motor function recovery and inhibiting depression after SCI, we aimed to determine the appropriate intensity of BWSTT. In this study, fixed durations, frequencies, and percentages of BWSTT with different speeds of BWSTT (7, 15, and 21 cm/s) were chosen to explore the appropriate intensity, which affected the recovery of motor function and antidepressant effects on SCI rats. Based on our results, BWSTT at 21 cm/s produced the best outcomes for motor function recovery and the spinal cord levels of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB). The antidepressant effects of BWSTT at 15 and 21 cm/s were confirmed based on the increasing sucrose preference, the time spent in the central area and social time, and reduced immobility time. BWSTT at 15 and 21 cm/s improved the modulation of the hypothalamic-pituitary-adrenal axis by decreasing serum corticosterone levels and increasing hippocampal glucocorticoid receptor levels. In addition, higher levels of neurogenesis-related proteins were observed in the hippocampus of the group subjected to BWSTT at 21 cm/s than in the other groups. Thus, BWSTT at 21 cm/s is a potentially favorable treatment that synchronously improves motor function recovery and exerts an antidepressant effect.
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http://dx.doi.org/10.1097/WNR.0000000000001543DOI Listing
December 2020

Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells.

Cell Death Dis 2020 10 30;11(10):937. Epub 2020 Oct 30.

Guangdong Key Laboratory for Genome Stability & Disease Prevention and Regional Immunity and Diseases, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong, 518060, People's Republic of China.

Gastric cancer (GC) is the most common cancer throughout the world. Despite advances of the treatments, detailed oncogenic mechanisms are largely unknown. In our previous study, we investigated microRNA (miR) expression profiles in human GC using miR microarrays. We found miR-192/215 were upregulated in GC tissues. Then gene microarray was implemented to discover the targets of miR-192/215. We compared the expression profile of BGC823 cells transfected with miR-192/215 inhibitors, and HFE145 cells transfected with miR-192/-215 mimics, respectively. SET8 was identified as a proposed target based on the expression change of more than twofold. SET8 belongs to the SET domain-containing methyltransferase family and specifically catalyzes monomethylation of H4K20me. It is involved in diverse functions in tumorigenesis and metastasis. Therefore, we focused on the contributions of miR-192/215/SET8 axis to the development of GC. In this study, we observe that functionally, SET8 regulated by miR-192/215 is involved in GC-related biological activities. SET8 is also found to trigger oncogene-induced senescence (OIS) in GC in vivo and in vitro, which is dependent on the DDR (DNA damage response) and p53. Our findings reveal that SET8 functions as a negative regulator of metastasis via the OIS-signaling pathway. Taken together, we investigated the functional significance, molecular mechanisms, and clinical impact of miR-192/215/SET8/p53 in GC.
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http://dx.doi.org/10.1038/s41419-020-03130-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599338PMC
October 2020

SUFU mediates EMT and Wnt/β-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer.

Cell Cycle 2020 Oct 5;19(20):2720-2733. Epub 2020 Oct 5.

Guangdong Key Laboratory for Genome Stability & Disease Prevention, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Shenzhen University School of Medicine , Shenzhen, Guangdong, China.

The poor prognosis of late gastric carcinomas (GC) underscores the necessity to identify novel biomarkers for earlier diagnosis and effective therapeutic targets. MiRNA-324-5p has been shown to be over-expressed in GC, however the biological function of miRNA-324-5p implicated in gastric cancer and its downstream targets were not well understood. Wnt/β-catenin signaling pathway is aberrantly regulated in GC. We sought to explore if miRNA-324-5p promotes oncogenesis through modulating Wnt signaling and EMT. MiRNA-324-5p is highly expressed in GC based on qRT-PCR and TCGA data. In addition, in vitro cell proliferation, cell migration assays and in vivo animal exenograft were executed to show that miRNA-324-5p is an oncogenic miRNA in GC. MiRNA-324-5p activates Wnt signaling and induces EMT in GC. Further, SUFU was identified as a target of miRNA-324-5p confirmed by western blotting and luciferase assays. Spearson analysis and TCGA data indicate that the expression of SUFU is negatively associated with the expression of miRNA-324-5p. Rescue experiments were performed to determine if SUFU mediates the Wnt activation, EMT and oncogenic function of miRNA-324-5p. MiRNA-324-5p inhibitors plus SUFU siRNAs rescue partially the inhibitory effect on Wnt signaling and EMT caused by miRNA-324-5p inhibitors. Finally, the suppression of cell proliferation, migration, and colony formation ability induced by miRNA-324-5p inhibitors is alleviated by addition of SUFU siRNAs. In summary, miRNA-324-5p is overexpressed and exerts cell growth and migration-promoting effects through activating Wnt signaling and EMT by targeting SUFU in GC. It represents a potential miRNA with an oncogenic role in human gastric cancer.
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http://dx.doi.org/10.1080/15384101.2020.1826632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644164PMC
October 2020

Paraesophageal hernia.

Med Clin (Barc) 2020 Aug 19. Epub 2020 Aug 19.

Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing 100034, China. Electronic address:

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http://dx.doi.org/10.1016/j.medcli.2020.06.049DOI Listing
August 2020

WITHDRAWN: Novel long-acting BF-30 conjugate corrects pancreatic carcinoma via cytoplasmic membrane permeabilization and DNA-binding in tumor-bearing mice.

Life Sci 2020 Aug 13:118278. Epub 2020 Aug 13.

The First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address:

This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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http://dx.doi.org/10.1016/j.lfs.2020.118278DOI Listing
August 2020

MRI-Based Deep-Learning Model for Distant Metastasis-Free Survival in Locoregionally Advanced Nasopharyngeal Carcinoma.

J Magn Reson Imaging 2021 01 9;53(1):167-178. Epub 2020 Aug 9.

Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Background: Distant metastasis is the primary cause of treatment failure in locoregionally advanced nasopharyngeal carcinoma (LANPC).

Purpose: To develop a model to evaluate distant metastasis-free survival (DMFS) in LANPC and to explore the value of additional chemotherapy to concurrent chemoradiotherapy (CCRT) for different risk groups.

Study Type: Retrospective.

Population: In all, 233 patients with biopsy-confirmed nasopharyngeal carcinoma (NPC) from two hospitals.

Field Strength: 1.5T and 3T.

Sequence: Axial T -weighted (T -w) and contrast-enhanced T -weighted (CET -w) images.

Assessment: Deep learning was used to build a model based on MRI images (including axial T -w and CET -w images) and clinical variables. Hospital 1 patients were randomly divided into training (n = 169) and validation (n = 19) cohorts; Hospital 2 patients were assigned to a testing cohort (n = 45). LANPC patients were divided into low- and high-risk groups according to their DMFS (P < 0.05). Kaplan-Meier survival analysis was performed to compare the DMFS of different risk groups and subgroup analysis was performed to compare patients treated with CCRT alone and treated with additional chemotherapy to CCRT in different risk groups, respectively.

Statistical Tests: Univariate analysis was performed to identify significant clinical variables. The area under the receiver operating characteristic (ROC) curve (AUC) was used to assess the model performance.

Results: Our deep-learning model integrating the deep-learning signature, node (N) stage (from TNM staging), plasma Epstein-Barr virus (EBV)-DNA, and treatment regimens yielded an AUC of 0.796 (95% confidence interval [CI]: 0.729-0.863), 0.795 (95% CI: 0.540-1.000), and 0.808 (95% CI: 0.654-0.962) in the training, internal validation, and external testing cohorts, respectively. Low-risk patients treated with CCRT alone had longer DMFS than patients treated with additional chemotherapy to CCRT (P < 0.05).

Data Conclusion: The proposed deep-learning model, based on MRI features and clinical variates, facilitated the prediction of DMFS in LANPC patients.

Level Of Evidence: 3.

Technical Efficacy Stage: 4.
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http://dx.doi.org/10.1002/jmri.27308DOI Listing
January 2021

Left/right difference in the course and division of the pulmonary arterial branches in the lung upper lobe: A study using human embryos and early fetuses.

J Anat 2020 11 24;237(5):854-860. Epub 2020 Jul 24.

Department of Anatomy, Tokyo Dental College, Tokyo, Japan.

Although left/right differences in a configuration of the pulmonary artery (PA) and its branches are well known, there is little information as to when and how such differences are established. Examination of serial sagittal sections of 25 embryos and fetuses at 6-7 weeks of gestation demonstrated that, at O'Rahilly stages 18-20, the right earliest first branch of PA originated in the anterior side of the upper lobar bronchus and overlay the upper bronchi, in contrast to the left branch which was located posteriorly and constricted medially by the upper posterior bronchus B1 + 2b. The right earliest branch was most likely to correspond to the future superior trunk, while the left branch might be a lingual artery. At stages 21-23, the upper posterior parenchyma was still underdeveloped in the left lung, since the ductus arteriosus and the left common cardinal vein seemed to make the left upper thoracic cavity narrow. Conversely, in the right lung, the thick S2 seemed to require a double arterial supply from both the superior and inferior arterial trunks. On the left, A3 originated at the lung apex and took a long descending course along the lung anterior surface. This high position of A3 might soon be corrected by an increased volume of S3. Overall, in contrast to the lower and middle lobes, early-developed branches of the PA did not accompany upper segmental and subsegmental bronchi. A mechanism "differential growth" seemed to explain how to correct the fetal morphology to provide the adult morphology with variations.
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http://dx.doi.org/10.1111/joa.13264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542188PMC
November 2020

Downregulation of CRABP2 Inhibit the Tumorigenesis of Hepatocellular Carcinoma In Vivo and In Vitro.

Biomed Res Int 2020 24;2020:3098327. Epub 2020 Jun 24.

Department of General Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China.

Cellular retinoic acid-binding protein 2 (CRABP2) binds retinoic acid (RA) in the cytoplasm and transports it into the nucleus, allowing for the regulation of specific downstream signal pathway. Abnormal expression of CRABP2 has been detected in the development of several tumors. However, the role of CRABP2 in hepatocellular carcinoma (HCC) has never been revealed. The current study aimed to investigate the role of CRABP2 in HCC and illuminate the potential molecular mechanisms. The expression of CRABP2 in HCC tissues and cell lines was detected by western blotting and immunohistochemistry assays. Our results demonstrated that the expression levels of CRABP2 in HCC tissues were elevated with the tumor stage development, and it was also elevated in HCC cell lines. To evaluate the function of CRABP2, shRNA-knockdown strategy was used in HCC cells. Cell proliferation, metastasis, and apoptosis were analyzed by CCK-8, EdU staining, transwell, and flow cytometry assays, respectively. Based on our results, knockdown of CRABP2 by shRNA resulted in the inhibition of tumor proliferation, migration, and invasion in vitro, followed by increased tumor apoptosis-related protein expression and decreased ERK/VEGF pathway-related proteins expression. CRABP2 silencing in HCC cells also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of CRABP2 in the development and development of HCC. Based on our findings, CRABP2 may be used as a novel diagnostic biomarker, and regulation of CRABP2 in HCC may provide a potential molecular target for the therapy of HCC.
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http://dx.doi.org/10.1155/2020/3098327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334762PMC
April 2021

Development of Different Methods for Preparing Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy.

Front Immunol 2020 23;11:1069. Epub 2020 Jun 23.

Department of Microbiology and Biochemical Pharmacy, National Engineering Research Center of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.

() is becoming a common global concern due to the emergence of multi-drug or pan-drug resistant strains. Confronting the issue of antimicrobial resistance by developing vaccines against the resistant pathogen is becoming a common strategy. In this study, different methods for preparing outer membrane vesicles (AbOMVs) vaccines were developed. sOMV (spontaneously released AbOMV) was extracted from the culture supernatant, while SuOMV (sucrose-extracted AbOMV) and nOMV (native AbOMV) were prepared from the bacterial cells. Three AbOMVs exhibited significant differences in yield, particle size, protein composition, and LPS/DNA content. To compare the protective efficacy of the three AbOMVs, groups of mice were immunized either intramuscularly or intranasally with each AbOMV. Vaccination via both routes conferred significant protection against lethal and sub-lethal challenge. Moreover, intranasal vaccination provided more robust protection, which may be attributed to the induction of significant sIgA response in mucosal sites. Among the three AbOMVs, SuOMV elicited the highest level of protective immunity against infection, whether intramuscular or intranasal immunization, which was characterized by the expression of the most profound specific serum IgG or mucosal sIgA. Taken together, the preparation method had a significant effect on the yield, morphology, and composition of AbOMVs, that further influenced the protective effect against infection.
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http://dx.doi.org/10.3389/fimmu.2020.01069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324643PMC
March 2021

Increased Alcohol Consumption in Mice Lacking Sodium Bicarbonate Transporter NBCn1.

Sci Rep 2020 07 3;10(1):11017. Epub 2020 Jul 3.

Department of Physiology, Emory University School of Medicine, Atlanta, GA, 30322, USA.

The previous reports on an addiction vulnerability marker in the human SLC4A7 gene encoding the Na/HCO transporter NBCn1 suggest that this pH-regulating protein may affect alcohol-related behavior and response. Here, we examined alcohol consumption and sensitivity to the sedative effects of alcohol in male NBCn1 knockout mice. These mice displayed lower pH in neurons than wildtype controls, determined by intracellular pH in hippocampal neuronal cultures. Neurons from knockout mice had a higher action potential threshold and a more depolarized membrane potential, thus reducing membrane excitability. In a two-bottle free choice procedure, knockout mice consumed more alcohol than controls and consistently increased alcohol consumption after repeated alcohol deprivation periods. Quinine and sucrose preference was similar between genotypes. Knockout mice showed increased propensity for alcohol-induced conditioned place preference. In loss of righting reflex assessment, knockout mice revealed increased sensitivity to alcohol-induced sedation and developed tolerance to the sedation after repeated alcohol administrations. Furthermore, chronic alcohol consumption caused NBCn1 downregulation in the hippocampus and striatum of mice and humans. These results demonstrate an important role of NBCn1 in regulation of alcohol consumption and sensitivity to alcohol-induced sedation.
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http://dx.doi.org/10.1038/s41598-020-67291-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335059PMC
July 2020

Drug treatment of coronavirus disease 2019 (COVID-19) in China.

Eur J Pharmacol 2020 Sep 27;883:173326. Epub 2020 Jun 27.

National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, 400038, PR China. Electronic address:

Since December 2019, the coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread throughout China as well as other countries. More than 8,700,000 confirmed COVID-19 cases have been recorded worldwide so far, with much more cases popping up overseas than those inside. As the initial epicenter in the world, China has been combating the epidemic for a relatively longer period and accumulated valuable experience in prevention and control of COVID-19. This article reviewed the clinical use, mechanism and efficacy of the clinically approved drugs recommended in the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (DTPNCP) released by National Health Commission of P.R.China, and the novel therapeutic agents now undergoing clinical trials approved by China National Medical Products Administration (NMPA) to evaluate experimental treatment for COVID-19. Reviewing the progress in drug development for the treatment against COVID-19 in China may provide insight into the epidemic control in other countries.
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http://dx.doi.org/10.1016/j.ejphar.2020.173326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319927PMC
September 2020

Tonic GABA-activated synaptic and extrasynaptic currents in dentate gyrus granule cells and CA3 pyramidal neurons along the mouse hippocampal dorsoventral axis.

Hippocampus 2020 Nov 13;30(11):1146-1157. Epub 2020 Jun 13.

Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.

The hippocampus is a medial temporal lobe structure in the brain and is widely studied for its role in memory and learning, in particular, spacial memory and emotional responses. It was thought to be a homogenous structure but emerging evidence shows differentiation along the dorsoventral axis and even microdomains for functional and cellular markers. We have examined in two cell-types of the hippocampal projection neurons, the dentate gyrus (DG) granule cells and CA3 pyramidal neurons, if the GABA-activated tonic current density varied between the dorsal (septal) and the ventral (temporal) poles of the male mouse hippocampus. Tonic synaptic currents, arising from spontaneous and miniature inhibitory postsynaptic currents (sIPSC, mIPSC), and extrasynaptic tonic currents were evaluated. The results revealed different levels of sIPSC but not mIPSC density between the dorsal and ventral hippocampal neurons for both the DG granule cells and the CA3 pyramidal neurons. The extrasynaptic tonic current density was larger in the DG granule cells as compared to the CA3 pyramidal neurons but did not vary between the dorsal and ventral regions. IPSC bursting was observed in both cell-types in the ventral hippocampus but was more common in the CA3 pyramidal neurons. Only in the dorsal DG granule cells was the level of the sIPSC and mIPSC density similar. The results indicate that the tonic GABAergic inhibition is particularly strong in the ventral hippocampal DG granule cells and enhanced in the dorsal as compared to the ventral hippocampal CA3 pyramidal neurons.
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http://dx.doi.org/10.1002/hipo.23245DOI Listing
November 2020

"Effectiveness of Jinying capsule on pelvic inflammatory disease in patients with symptom pattern of damp and heat accumulation: a double-blinded, multicenter, randomized, placebo-controlled clinical trial".

J Tradit Chin Med 2020 06;40(3):432-439

Department of Gynecology, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China.

Objective: To evaluate the therapeutic effectiveness and safety of Jinying capsule on pelvic inflammatory disease (PID) in patients with symptoms identified as the pattern of damp and heat accumulation in terms of Traditional Chinese Medicine (TCM).

Methods: We conducted a double-blinded, multicenter, randomized, placebo-controlled clinical trial which included 155 patients diagnosed with PID and identified as symptom pattern of damp and heat accumulation. They were randomly divided into experimental group (n = 78) and control group (n = 77) according to a random number table. The treatment lasted for a period of 28 d. The experimental group was given Jinying capsules and oral levofloxacin plus oral metronidazole for first 7 d. They continued with Jinying capsules and levofloxacin placebo and metronidazole placebo for another 7 d. For the remaining 14 d, they continued with Jinying capsules only. Whereas, the control group was treated with oral levofloxacin and metronidazole and Jinying capsule placebo for the first 14 d in the same way as the experimental group and then continued with Jinying capsule placebo only for the remaining 14 d. The clinical efficacy was assessed using McCormack scale, TCM symptom pattern scores, physicochemical indexes including white blood cell and erythrocyte sedimentation rate, C-reaction protein, smear of vaginal discharge, and pelvic ultrasound.

Results: Comparing McCormack scale between both groups after treatment, the difference in curative effect between both groups was significant (P = 0.0269). The cure rate of the experimental group and control group is 76.32% and 59.46% respectively at week 4. Comparing TCM symptom pattern scores between both groups before and after treatment, the differences in total effective rate were both significant (P < 0.05). The curative effect rate of experimental group is 2.63% and 13.70% of the control group at week 1 (P = 0.0131), and 73.33% of the experimental group and 56.94% of the control group at week 4 (P = 0.0369). No significant differences were found between the two groups on the Physicochemical indexes (all P > 0.05). No adverse events or reactions occurred in the experimental groups.

Conclusion: Jinying capsule can reduce the dosage of antibiotics needed for PID treatment, and improve the symptoms in PID patients.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2020.03.011DOI Listing
June 2020

Exosomal miR-9-5p secreted by bone marrow-derived mesenchymal stem cells alleviates osteoarthritis by inhibiting syndecan-1.

Cell Tissue Res 2020 Jul 6;381(1):99-114. Epub 2020 May 6.

Department of Orthopaedics, Dashiqiao Central Hospital, Shenyang, 115100, People's Republic of China.

Mesenchymal stem cells (MSCs) have been demonstrated to serve as targets for the treatment of osteoarthritis (OA) and exosomes derived from MSCs also display chondroprotective effects. This study aims to investigate the regulatory role of exosomal microRNA-9-5p (miR-9-5p) secreted by bone marrow-derived MSCs (BM-MSCs) on OA in a rat model induced by anterior cruciate ligament/medial collateral ligament transection. Luciferase reporter assay was conducted to verify the putative miR-9-5p binding sites to 3'UTR of syndecan-1 (SDC1). Additionally, an intra-articular injection of miR-9-5p carried by BM-MSC-derived exosomes or liposomes into rats with OA-like damage was performed to ascertain the role of exosomal miR-9-5p and a gain-of-function study of SDC1 was carried out to explore the potential mechanism in relation to SDC1. Subsequently, the expression of SDC1 was determined and the levels of inflammatory factors (IL-1, IL-6, TNF-α and CRP) and oxidative stress injury indicators (NO, MDA, iNOS, COX2 and SOD), the contents of AKP as well as the levels of OA-related factors (MMP-13, COMP and OCN) were measured. Injection of miR-9-5p-contained exosomes resulted in an alleviation of inflammation and OA-like damage, which was evidenced by downregulated levels of inflammatory factors, reduced oxidative stress injury and decreased OCN, MMP-13, COMP and AKP levels. As a target gene of miR-9-5p, the upregulation of SDC1 led to aggravation of inflammation and OA-like damage, which is opposite to exosomal miR-9-5p. To conclude, these findings suggest the anti-inflammatory and chondroprotective effects of BM-MSC-derived exosomal miR-9-5p on OA via regulation of SDC1.
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http://dx.doi.org/10.1007/s00441-020-03193-xDOI Listing
July 2020