Inactivation activity and mechanism of pulsed light against Alicyclobacillus acidoterrestris vegetative cells and spores in concentrated apple juice.

Alicyclobacillus acidoterrestris has received much attention due to its unique thermo-acidophilic property and implication in the spoilage of pasteurized juices. The objective of this study was to evaluate the sterilization characteristics and mechanisms of pulsed light (PL) against A. acidoterrestris vegetative cells and spores in apple juice. The results indicated that bacteria cells in apple juice (8-20°Brix) can be completely inactivated within the fluence range of 20.25-47.25 J/cm2, which mainly depended on the soluble solids content (SSC) of juice, and the spores in apple juice (12°Brix) can be completely inactivated by PL with the fluence of 54.00 J/cm2. The PL treatment can significantly increase the leakage of reactive oxygen species (ROS) and proteins from cells and spores. Fluorescence studies of bacterial adenosine triphosphate (ATP) indicated that the loss of ATP was evident. Scanning electron microscopy and confocal laser scanning microscope presented that PL-treated cells or spores had serious morphological damage, which reduced the integrity of cell membrane and led to intracellular electrolyte leakage. In addition, there were no significant negative effects on total sugars, total acids, total phenols, pH value, SSC and soluble sugars, and organic acid content decreased slightly during the PL treatment. The contents of esters and acids in aroma components had a certain loss, while that of alcohols, aldehydes and ketones were increased. These results demonstrated that PL treatment can effectively inactivate the bacteria cells and spores in apple juice with little effect on its quality. This study provides an efficient method for the inactivation of A. acidoterrestris in fruit juice.

Whole Exome Sequencing reveals clinically important pathogenic mutations in DNA repair genes across lung cancer patients.

Lung cancer remains a substantial health challenge, with distinct genetic factors influencing disease susceptibility and progression. This study aimed to decipher the landscape of DNA repair gene mutations in Pakistani lung cancer patients using Whole Exome Sequencing (WES) and to investigate their potential functional implications through downstream analyses. WES analysis of genomic DNA from 15 lung cancer patients identified clinically important pathogenic mutations in 6 DNA repair genes, including, BReast CAncer gene 1 (BRCA1), BReast CAncer gene 2 (BRCA2), Excision Repair Cross Complementing rodent repair deficiency, complementation group 6 (ERCC6), Checkpoint Kinase 1 (CHEK1), mutY DNA glycosylase (MUTYH), and RAD51D (RAD51 Paralog D). Kaplan-Meier (KM) analysis showed that pathogenic mutations in BRCA1, BRCA2, ERCC6, CHEK1, MUTYH, and RAD51D genes were the prognostic biomarkers of worse OS in lung cancer patients. To explore the functional impact of these mutations, we performed Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Immunohistochemistry (IHC) analyses. Our results revealed a down-regulation in the expression of the mutated genes, indicating a potential link between the identified mutations and reduced gene activity. This down-regulation could contribute to compromised DNA repair efficiency, thereby fostering genomic instability in lung cancer cells. Furthermore, targeted bisulfite sequencing analysis was employed to assess the DNA methylation status of the mutated genes. Strikingly, hypermethylation in the promoters of BRCA1, BRCA2, ERCC6, CHEK1, MUTYH, and RAD51D was observed across lung cancer samples harboring pathogenic mutations, suggesting the involvement of epigenetic mechanism underlying the altered gene expression. In conclusion, this study provides insights into the genetic landscape of DNA repair gene mutations in Pakistani lung cancer patients. The observed pathogenic mutations in BRCA1, BRCA2, ERCC6, CHEK1, MUTYH, and RAD51D, coupled with their down-regulation and hypermethylation, suggest a potential convergence of genetic and epigenetic factors driving genomic instability in lung cancer cells. These findings contribute to our understanding of lung cancer susceptibility and highlight potential avenues for targeted therapeutic interventions in Pakistani lung cancer patients.

Comparison of voiding vesicoureteral urosonography with fluoroscopic voiding cystourethrography in children with vesicoureteral reflux.

Objective: To evaluate the value and compliance rate of voiding vesicoureteral urosonography in pediatric vesicoureteral reflux (VUR). Methods: This is a retrospective study. A total of 80 children with high-risk VUR admitted to Children's Hospital affiliated to Capital Medical University from December 2018 to December 2020 were selected. All patients underwent voiding urosonography (VUS) and fluoroscopic voiding cystourethrography (VCUG). The sensitivity and compliance of voiding vesicoureteral urosonography were compared, and its application value was evaluated. Results: A total of 160 PUUs were examined, and all cases were normal. Among them, 56 PUUs had reflux (35.00%, 56/160), 46 PUUs had reflux under both examination methods (28.75%, 46/160), and 10 PUUs were only detected under VUS (6.25%, 10/160). Thirty-four cases of VUR (42.50%, 34/80) were diagnosed by VUS, among which 15 cases were bilateral reflux and 4 cases were unilateral reflux. Twenty-five cases (35.00%, 25/80) were diagnosed by VCUG, among which 10 cases were bilateral regurgitation and five cases were unilateral regurgitation. No significant difference was observed in the detection rate of reflux between the two methods (P=0.432). A total of 146 PUUs were found to be consistent between the two methods (91.25%, 160), including 2 Grade-I reflux, 6 Grade-II reflux, 14 Grade-III reflux, 12 Grade-IV reflux, eight Grade-V reflux, and 104 without reflux, demonstrating SATISFACTORY consistency between the two groups (Kappa=0.885). Conclusion: Voiding vesicoureteral urosonography has a high coincidence rate in the detection of vesicoureteral reflux in children.

A phase I/II clinical trial on the efficacy and safety of NKT cells combined with gefitinib for advanced EGFR-mutated non-small-cell lung cancer.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, have achieved good efficacy in EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients, but eventual drug resistance is inevitable. Thus, new TKI-based combination therapies should be urgently explored to extend the overall survival time of these patients. CD8 + CD56+ natural killer T (NKT) cells are a natural and unique subset of lymphocytes in humans that present characteristics of T and NK cells and exert cytotoxicity on tumour cells in a granzyme B-dependent manner. The aim of this trial was to explore the efficacy and safety of CD8 + CD56+ NKT cell immunotherapy combined with gefitinib in patients with advanced EGFR-mutated NSCLC. METHODS: The study was designed as a prospective, randomized, controlled, open-label, phase I/II trial that includes 30 patients with EGFR mutation-positive stage III/IV NSCLC. All patients will be randomized in blocks at a 1:1 ratio and treated with gefitinib 250 mg/day monotherapy or combination therapy with allogeneic CD8 + CD56+ NKT cell infusions twice per month for 12 cycles or until disease progression occurs. The effectiveness of this treatment will be evaluated based on by progression-free survival (PFS), the time to progression (TTP), overall response rate (ORR), disease control rate (DCR) and overall survival (OS). The safety of the trail is being assessed based on adverse events (AEs). Recruitment and data collection, which started in December 2017, are ongoing. DISCUSSION: Although immunotherapy, including programmed death-1/programmed death-1 ligand (PD-1/PD-L1) immunotherapy, has been used for NSCLC treatment with or without EGFR-TKIs, its clear efficacy still has not been shown. Assessing the safety and therapeutic potential of allogeneic CD8 + CD56+ NKT killer cells in combination with EGFR-TKIs in NSCLC will be of great interest. TRIAL REGISTRATION: This trial (Phase I/II Trails of NKT Cell in Combination With Gefitinib For Non Small Cell Lung Cancer) was registered on 21 November 2017 with www.chictr.org.cn , ChiCTR-IIR-17013471 .

LncRNA lnc-ISG20 promotes renal fibrosis in diabetic nephropathy by inducing AKT phosphorylation through miR-486-5p/NFAT5.

Long non-coding RNA (lncRNA) lnc-ISG20 has been found aberrantly up-regulated in the glomerular in the patients with diabetic nephropathy (DN). We aimed to elucidate the function and regulatory mechanism of lncRNA lnc-ISG20 on DN-induced renal fibrosis. Expression patterns of lnc-ISG20 in kidney tissues of DN patients were determined by RT-qPCR. Mouse models of DN were constructed, while MCs were cultured under normal glucose (NG)/high glucose (HG) conditions. The expression patterns of fibrosis marker proteins collagen IV, fibronectin and TGF-ß1 were measured with Western blot assay. In addition, the relationship among lnc-ISG20, miR-486-5p, NFAT5 and AKT were analysed using dual-luciferase reporter assay and RNA immunoprecipitation. The effect of lnc-ISG20 and miR-486/NFAT5/p-AKT axis on DN-associated renal fibrosis was also verified by means of rescue experiments. The expression levels of lnc-ISG20 were increased in DN patients, DN mouse kidney tissues and HG-treated MCs. Lnc-ISG20 silencing alleviated HG-induced fibrosis in MCs and delayed renal fibrosis in DN mice. Mechanistically, miR-486-5p was found to be a downstream miRNA of lnc-ISG20, while miR-486-5p inhibited the expression of NFAT5 by binding to its 3'UTR. NFAT5 overexpression aggravated HG-induced fibrosis by stimulating AKT phosphorylation. However, NFAT5 silencing reversed the promotion of in vitro and in vivo fibrosis caused by lnc-ISG20 overexpression. Our collective findings indicate that lnc-ISG20 promotes the renal fibrosis process in DN by activating AKT through the miR-486-5p/NFAT5 axis. High-expression levels of lnc-ISG20 may be a useful indicator for DN.

Exosomal microRNA-16-5p from human urine-derived stem cells ameliorates diabetic nephropathy through protection of podocyte.

Diabetic nephropathy (DN) remains one of the severe complications associated with diabetes mellitus. It is worthwhile to uncover the underlying mechanisms of clinical benefits of human urine-derived stem cells (hUSCs) in the treatment of DN. At present, the clinical benefits associated with hUSCs in the treatment of DN remains unclear. Hence, our study aims to investigate protective effect of hUSC exosome along with microRNA-16-5p (miR-16-5p) on podocytes in DN via vascular endothelial growth factor A (VEGFA). Initially, miR-16-5p was predicated to target VEGFA based on data retrieved from several bioinformatics databases. Notably, dual-luciferase report gene assay provided further verification confirming the prediction. Moreover, our results demonstrated that high glucose (HG) stimulation could inhibit miR-16-5p and promote VEGFA in human podocytes (HPDCs). miR-16-5p in hUSCs was transferred through the exosome pathway to HG-treated HPDCs. The viability and apoptosis rate of podocytes after HG treatment together with expression of the related factors were subsequently determined. The results indicated that miR-16-5p secreted by hUSCs could improve podocyte injury induced by HG. In addition, VEGA silencing could also ameliorate HG-induced podocyte injury. Finally, hUSC exosomes containing overexpressed miR-16-5p were injected into diabetic rats via tail vein, followed by qualification of miR-16-5p and observation on the changes of podocytes, which revealed that overexpressed miR-16-5p in hUSCs conferred protective effects on HPDCs in diabetic rats. Taken together, the present study revealed that overexpressed miR-16-5p in hUSC exosomes could protect HPDCs induced by HG and suppress VEGFA expression and podocytic apoptosis, providing fresh insights for novel treatment of DN.

Adipose mesenchymal stem cell-derived extracellular vesicles containing microRNA-26a-5p target TLR4 and protect against diabetic nephropathy.

Diabetic nephropathy (DN) is a complication of diabetes that is increasing in prevalence in China. Extracellular vesicles (EVs) carrying microRNAs (miRs) may represent a useful tool in the development of therapies for DN. Here, we report that EVs released by adipose-derived mesenchymal stem cells (ADSCs) during DN contain a microRNA, miR-26a-5p, that suppresses DN. Using bioinformatic analyses, we identified differentially expressed miRs in EVs from ADSCs and in DN and predicted downstream regulatory target genes. We isolated mesenchymal stem cells (MSCs) from adipose tissues and collected EVs from the ADSCs. We exposed mouse glomerular podocytes and MP5 cells to high glucose (HG), ADSC-derived EVs, miR-26a-5p inhibitor/antagomir, Toll-like receptor 4 (TLR4) plasmids, or the NF-κB pathway activator (phorbol-12-myristate-13-acetate, or PMA). We used the cell counting kit-8 (CCK-8) assay and flow cytometry to investigate the impact of miR-26a-5p on cell viability and apoptosis and validated the results of these assays with in vivo experiments in nude mice. We found that in DN, miR-26a-5p is expressed at very low levels, whereas TLR4 is highly expressed. Of note, EVs from ADSCs ameliorated the pathological symptoms of DN in diabetic mice and transferred miR-26a-5p to HG-induced MP5 cells, improving viability while suppressing the apoptosis of MP5 cells. We also found that miR-26a-5p protects HG-induced MP5 cells from injury by targeting TLR4, inactivating the NF-κB pathway, and downregulating vascular endothelial growth factor A (VEGFA). Moreover, ADSC-derived EVs transferred miR-26a-5p to mouse glomerular podocytes, which ameliorated DN pathology. These findings suggest that miR-26a-5p from ADSC-derived EVs protects against DN.

Upregulation of lncRNA SUMO1P3 promotes proliferation, invasion and drug resistance in gastric cancer through interacting with the CNBP protein.

Gastric cancer (GC) is one type of the most common malignancies in the world. In the process of exploring the pathological mechanism of GC and searching for treatment methods, long non-coding RNAs (lncRNAs) display significant participation. Small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) is a newly identified lncRNA, of which the biological role and underlying mechanism in GC progression have not been elucidated. Here, through the comparisons between GC patients' tumor and normal tissue samples, as well as normal gastric mucosal and GC cell lines, we confirmed a significant upregulation of SUMO1P3 in GC tissues and cell lines. Meanwhile, significant upregulation of SUMO1P3 was observed in advanced GC patients, and patients with high level of SUMO1P3 displayed a poor survival rate. Next, gain- and loss-of-function experiments were performed in GC cells, and the results exhibited that SUMO1P3 positively regulated proliferation and invasion of GC cells. Then, we constructed drug-resistant GC cell strains and explore the role of SUMO1P3 in the resistance of GC cells to cisplatin (DDP) and 5-fluorouracil (5-Fu). Finally, bioinformatics analysis and RNA pull-down assay demonstrated that SUMO1P3 could directly interact with cellular nucleic acid binding protein (CNBP), thus positively regulating CNBP downstream oncogenes c-myc and cyclin D1 (CCND1). Our findings indicate that SUMO1P3 promotes proliferation, invasion and drug resistance of GC cells by interacting with CNBP, which reveals a potential prognostic biomarker and a novel therapeutic target for GC.

Astilbin Inhibits High Glucose-Induced Inflammation and Extracellular Matrix Accumulation by Suppressing the TLR4/MyD88/NF-κB Pathway in Rat Glomerular Mesangial Cells.

Diabetic nephropathy (DN) is characterized by inflammatory responses and extracellular matrix (ECM) accumulation. Astilbin is an active natural compound and possesses anti-inflammatory activity. The aim of this study was to evaluate the anti-inflammatory effect of astilbin on high glucose (HG)-induced glomerular mesangial cells and the potential mechanisms. The results showed that HG induced cell proliferation of HBZY-1 cells in a time-dependent manner, and astilbin inhibited HG-induced cell proliferation. The expression and secretion of inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), and ECM components, including collagen IV (Col IV) and fibronectin (FN), were induced by HG. Moreover, TGF-ß1 and CTGF were also induced by HG. The induction by HG on inflammatory response and ECM accumulation was inhibited after astilbin treatment. Astilbin treatment also attenuated HG-induced decrease in expression of matrix metalloproteinase (MMP)-2 and MMP-9. The TLR4/MyD88/NF-κB pathway was activated by HG, and the inhibitor of TLR4 exhibited the same effect to astilbin on reversing the induction of HG. TLR4 overexpression attenuated the effect of astilbin on HG-induced inflammatory cytokine production and ECM accumulation. The results suggested that astilbin attenuated inflammation and ECM accumulation in HG-induced rat glomerular mesangial cells via inhibiting the TLR4/MyD88/NF-κB pathway. This work provided evidence that astilbin can be considered as a potential candidate for DN therapy.

Astilbin inhibits high glucose-induced autophagy and apoptosis through the PI3K/Akt pathway in human proximal tubular epithelial cells.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. It has been found that astilbin, a flavonoid compound, exerts a protective effect on DN. However, the role of astilbin in autophagy during DN is unknown. The human proximal tubular epithelial cells (HK-2 cells) were treated with high glucose (HG, 30 mM) in the presence or absence of astilbin. Cell viability was measured by MTT assay. The autophagy was determined by detecting the expression of LC3-II and p62 using western blot. The cell apoptosis was evaluated by detecting the apoptosis rate, caspase-3 activity, and the expression of Bcl-2 and Bax. The expression levels of protein kinase B (Akt) and p-Akt were detected by western blot. To determine whether the phosphatidylinositol-3-kinase (PI3K)/Akt pathway was involved in the effect of astilbin, cells were treated with the inhibitor of Akt, LY294002. We found that astilbin (10 and 20 µM) did not affect the viability of HK-2 cells, but attenuated HG-induced cell viability. Astilbin attenuated HG-induced autophagy and apoptosis in HK-2 cells. The expression of p-Akt was inhibited by HG treatment, while the inhibitory effect of HG was attenuated by astilbin. Inhibition of the PI3K/Akt signaling resisted the effect of astilbin on HG-induced apoptosis and autophagy. In conclusion, astilbin attenuated HG-induced autophagy and apoptosis in HK-2 cells through the PI3K/Akt pathway. The results indicated that astilbin might be a new therapeutic agent and be useful for improving clinical management of DN.

Artesunate ameliorates high glucose-induced rat glomerular mesangial cell injury by suppressing the TLR4/NF-κB/NLRP3 inflammasome pathway.

Inflammatory response is important for the development and progression of diabetic nephropathy (DN). Artesunate (ART), an antimalarial drug, possesses anti-inflammatory effect and exhibits protective effect on chronic kidney diseases. However, the effect of ART on DN is unknown. The aim of the present study was to evaluate the effect and the molecular mechanism of ART on DN in an in vitro model. The rat mesangial cell line, HBZY-1, was induced by high glucose (HG; 30 mM d-glucose) in the presence or absence of ART (15 and 30 µg/ml) and incubated for 24 h. We found that HG induced the proliferation of HBZY-1 cells, while treatment with ART inhibited the cell proliferation. Treatment with ART inhibited HG-induced inflammatory cytokines production and expression of extracellular matrix (ECM). Besides, HG induced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and inhibited the superoxide dismutase (SOD) activity of HBZY-1 cells, and the effects were attenuated by ART treatment. ART decreased HG-induced the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), nuclear factor κB (NF-κB) p-p65, and nod-like receptor protein 3 (NLRP3). Inhibition of the TLR4/NF-κB pathway suppressed NLRP3 inflammasome in HBZY-1 cells. In conclusion, ART exhibited protective effect on HG-induced HBZY-1 cells by inhibiting the inflammatory response, oxidative stress and ECM accumulation. The TLR4/NF-κB/NLRP3 inflammasome pathway was involved in the protective effect of ART. The results suggested that ART might be a potential therapy agent for the DN treatment.

Potential of rhBMP-2 and dexamethasone-loaded Zein/PLLA scaffolds for enhanced in vitro osteogenesis of mesenchymal stem cells.

Nanofibers fabricated by electrospinning simulate the extracellular matrix of bone cells and so researchers have taken a keen interest in them for regenerating bone tissue. The aim of this study was to fabricate ideal Zein/PLLA nanofibers by coaxial electrospinning and to load them with bone morphogenetic protein 2 (BMP-2) and dexamethasone (DEX) for dual controlled-release for bone tissue engineering applications. Morphology, surface hydrophilicity and core-shell construction were analyzed by environmental scanning electron microscopy (SEM), water contact angle and transmission electron microscopy (TEM). The properties of the scaffolds were studied in terms of the viability, morphology and osteogenic differentiation of mesenchymal stem cells (MSCs) that had been cultured on nanofiber mats of the Zein/PLLA and were determined using SEM, CCK-8 assay, quantitative ALP staining analysis, quantitative mineral deposition using Alizarin red staining (ARS), immunofluorescence staining and western blot analysis of osteogenic proteins. In vitro studies demonstrated that the biological activity of DEX and BMP-2 was retained in the dual-drug-loaded nanofiber scaffolds. A large quantity of DEX was released in the first three days, while the release of BMP-2 lasted for more than 21 days. In vitro osteogenesis studies showed that the drug-loaded nanofiber scaffolds induced osteogenic differentiation. Furthermore, the dual controlled-release of BMP-2 and DEX enhanced the osteogenic differentiation of MSCs resulting from synergistic effects. Therefore, Zein/PLLA nanofiber scaffolds loaded with BMP-2 and DEX have great potential in bone tissue engineering applications.

Tangeretin inhibits high glucose-induced extracellular matrix accumulation in human glomerular mesangial cells.

Tangeretin (5, 6, 7, 8, 4'-pentamethoxyflavone), a natural compound extracted from citrus plants, has been shown to possess a variety of pharmacological activities, including anti-oxidant, anti-tumor, cytostatic and anti-diabetic properties. However, the role of tangeretin in diabetic nephropathy (DN) has not yet been investigated. This study was undertaken to elucidate the effects of tangeretin on high glucose (HG)-induced oxidative stress and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) and explore the underlying mechanisms. Our results showed that tangeretin significantly inhibited HG-induced the proliferation of MCs. In addition, tangeretin dramatically reduced the levels of reactive oxygen species (ROS) and malondialdhyde (MDA), and induced SOD activity, as well as inhibited the expression of fibronectin (FN) and collagen IV in HG-stimulated MCs. Furthermore, tangeretin efficiently prevented the activation of ERK signaling pathway in HG-stimulated MCs. Taken together, these data indicated that tangeretin inhibits HG-induced cell proliferation, oxidative stress and ECM expression in glomerular MCs, at least in part, through the inactivation of ERK signaling pathway. Therefore, tangeretin may be a potential agent in the treatment of DN.

Rhein inhibits malignant phenotypes of human renal cell carcinoma by impacting on MAPK/NF-κB signaling pathways.

BACKGROUND: Rhein, an anthraquinone derivative of rhubarb, is traditionally used in Chinese herbal medicine. Now emerging studies suggest its antitumor properties in many human cancers. The present study aims to investigate the antitumor role of Rhein and its possible mechanism in human renal cell carcinoma (RCC). MATERIALS AND METHODS: Three RCC cell lines (A489, 786-O and ACHN) were used as the cell models. We applied CCK-8, cell counting, colony formation, wound healing and Transwell assays to assess the antitumor roles of Rhein in RCC cells in vitro. The therapeutic efficacy of Rhein was further evaluated by intraperitoneal administrations in tumor formation of mice. Western blot was used to investigate the underlying mechanisms of action of Rhein. RESULTS: Rhein inhibited RCC cell proliferation in a dose- and time-dependent manner. It also suppressed RCC cell migration and invasion in vitro. Moreover, Rhein was able to inhibit tumor growth in nude mice by intraperitoneal administration in vivo. Mechanistically, the protein levels of phosphorylated MAPK (mitogen-activated protein kinase, extracellular signal-regulated kinase and c-Jun N-terminal kinase), phosphorylated Akt and two targets of NF-κB (nuclear factor kappa-light-chain enhancer of activated B cells) pathway, matrix metalloproteinase 9 and CCND1 were all markedly reduced by Rhein treatment. CONCLUSION: Rhein processed the antitumor effects in RCC cells by inhibiting cell proliferation, migration and invasion, and these tumor-suppressing functions might be mediated by MAPK/NF-κB signaling pathways.

An anionic single-walled metal-organic nanotube with an armchair (3,3) topology as an extremely smart adsorbent for the effective and selective adsorption of cationic carcinogenic dyes.

A novel discrete single-walled metal-organic nanotube (JLU-MONT1) with a rare armchair (3,3) carbon nanotube topology is successfully synthesized, which is further linked by hydrogen-bonds forming a 3D supramolecular architecture. Benefiting from its anionic skeletal features and open mesoporous channels (21 Å), JLU-MONT1 exhibits extremely high efficiency and capability to adsorb carcinogens basic red 9 and basic violet 14.

Protocatechuic acid ameliorates high glucose-induced extracellular matrix accumulation in diabetic nephropathy.

Protocatechuic acid (PCA), a phenolic compound of anthocyanins, was reported to possess various pharmacologic properties, including anti-oxidant, anti-inflammatory, anti-apoptosis, anti-diabetic and anti-tumor activities. However, the role of PCA in diabetic nephropathy remains elusive. The present study was conducted to evaluate the effects of PCA on extracellular matrix (ECM) accumulation in high glucose (HG)-induced human mesangial cells (MCs) and explore the possible mechanism. Our results demonstrated that PCA obviously inhibited HG-induced proliferation of MCs in a dose-dependent manner. In addition, PCA effectively reduced the protein expression levels of type IV collagen, laminin and fibronectin induced by HG, as well as decreased the levels of ROS and MDA in HG-stimulated MCs. Mechanistic studies showed that PCA efficiently down-regulated the phosphorylation level of p38 MAPK in HG-stimulated MCs. Taken together, our present study demonstrated that PCA protects MCs against HG damage might via inhibition of the p38 MAPK signaling pathway. Thus, PCA might be a beneficial agent for the prevention and treatment of diabetic nephropathy.

Transversus abdominis plane block versus local anaesthetic wound infiltration for postoperative analgesia: A systematic review and meta-analysis.

BACKGROUND: Transversus abdominis plane (TAP) block and local anaesthetic wound infiltration can provide effective pain relief at the wound site after surgery. However, the relative efficacy of two techniques for postoperative analgesia remains controversial. METHODS: We searched PUBMED, EMBASE and CENTRAL databases for randomized controlled trials (RCTs) comparing TAP block with wound infiltration for pain relief after surgery. The primary outcomes were pain scores at rest and on movement at 1, 8 and 24 hours postoperatively and cumulative morphine consumption over 24 hours. The secondary outcomes were time to first rescue analgesic, number of rescue analgesic use and opioids-related side-effects. RESULTS: Nine RCTs with a total of 500 participants were included. TAP block was associated with significant lower rest and dynamic pain scores at 8 hour [MD = -1.08, 95% CI (-1.89-0.26), P = 0.009] and 24 hour [MD = -0.83, 95% CI (-1.60, -0.06), P = 0.03] postoperatively than wound infiltration, but no significant difference was found at 1 hour [MD = -0.94, 95% CI (-1.97, 0.09), P = 0.08] postoperatively. In adults, TAP block significantly reduced 24-hour overall morphine consumption by 3.85 mg [MD = -3.85, 95% CI (-7.47, -0.22), P = 0.04] compared with wound infiltration. Subgroup analysis showed that adults received TAP block appeared to have lower rest pain scores at 24 hour than children (P = 0.008). CONCLUSION: TAP block provides superior analgesia compared with wound infiltration in the setting of a multimodal analgesic regimen. Subgroup analysis indicated that adults may have benefits additional to the analgesic effect than children.

Shenqifuzheng injection combined with chemotherapy in the treatment of advanced gastric cancer: a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of Shenqifuzheng (SQFZ) injection combined with chemotherapy in the treatment of advanced gastric cancer. MATERIALS AND METHODS: We conducted an electronic search by using PubMed, EMBASE, ASCO, ESMO and Chinese National Knowledge Infratructure (CNKI), databases. The randomized controlled trials about Shenqifuzheng injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced gastric cancer were reviewed and collected. Pooled odds ratio (OR) for the response rate and KPS improvement were calculated using the software MetaAnalyst 3.1. RESULTS: Fifteen trials met our inclusion criteria and finally included in this meta-analysis. The objective response rate (ORR) in patients treated with Shenqifuzheng injection combined with chemotherapy was much higher than that of chemotherapy only (OR = 1.66, 95% CI: 1.20-2.29) with statistical significance (P < 0.05). The pooled data showed the combined treatment can significant increase the Karnofsky score (KPS) compared with the chemotherapy only (OR = 3.74, 95% CI: 2.66-5.27 (P < 0.05). CONCLUSION: SQFZ injection combined with chemotherapy treatment regimen can improve the clinical efficacy and performance status in patients with advanced gastric cancer compared with chemotherapy alone.