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关键词： HLA   HLA-A*11:481   NGS novel allele  

摘要： The HLA-A*11:481 allele differs from HLA-A*11:01:01:01 by one nucleotide substitution in codon -8 in exon 1.

关键词： anakinra   normothermic machine perfusion   renal transplantation  

摘要： BackgroundThe interleukin 1 (IL-1) cytokine group plays a key role in sterile inflammation and may be an important target for transplant-related renal injury. This study examined the effects of anakinra, a non-specific IL-1 receptor antagonist, administered during normothermic machine perfusion (NMP) of porcine *** porcine kidneys (n = 5 pairs) underwent 15 min of warm ischemia plus 2 h of static cold storage in ice. Kidneys were then perfused with autologous whole blood using an ex vivo NMP platform. Kidneys were randomly allocated to receive anakinra or vehicle administered at the start of NMP. Cortical biopsies were collected at baseline before ischemic injury and at the end of NMP. Functional parameters were recorded and calculated, and inflammatory markers were measured by qPCR and ELISA *** NMP, there were no statistically significant differences in renal blood flow, urine output, creatinine clearance or fractional excretion of sodium in the anakinra and control groups. The administration of anakinra significantly downregulated transcriptional expression of IL-6, Fas ligand and intercellular adhesion molecule 1 (p = 0.029, 0.029, 0.028, respectively).ConclusionAnakinra, an IL-1 receptor blocker, successfully attenuated the downstream inflammatory and immune-mediated response within the kidney during NMP.

关键词： B10 cells   CD40/CD40L   low IgG   primary nephrotic syndrome   Th17/Treg  

摘要： Aim: This study aimed to investigate the contribution of interleukin (IL)-10-producing regulatory B cells (B10 cells) to the pathogenesis of PNS. Methods: The percentages of B10 cells, CD19(+)CD24(hi)CD27(+) B cells, CD19(+)CD24(hi)CD38(hi) B cells, CD19(+)CD24(hi)CD27(+)IL-10(+) B cells, CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells, Th17 cells, and regulatory T (Treg) cells within the peripheral blood mononuclear cells (PBMCs) from healthy subjects and PNS patients with active disease or in remission were analysed by flow cytometry. Results: The percentages and IL-10 production of circulating B10 cells and the two subsets were decreased in children with active PNS and returned to normal levels in PNS patients in remission. B10 cells and their subsets were negatively correlated with the Th17/Treg ratio. The percentages of B10pro+B10 cells, CD19(+)CD24(hi)CD27(+)IL-10(+) B cells, CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells, Th17 cells, Treg cells, and the Th17/Treg ratio did not significantly differ between groups after CpG and CD40L stimulation. However, in the presence of CpG and anti-CD40L mAb, the percentages of B10pro+B10 cells, CD19(+)CD24(hi)CD27(+)IL-10(+) B cells, CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells, and Treg cells were significantly reduced, whereas the Th17 cell percentage and the Th17/Treg ratio were significantly increased. Furthermore, the Th17/Treg ratio correlated negatively, whereas the percentages of B10 cells and their subsets correlated positively with serum immunoglobulin G (IgG) concentration. Conclusion: Our study demonstrates that the numbers of B10 cells and their ability to produce IL-10 are decreased, leading to an imbalance in the Th17/Treg ratio and low IgG levels, which may then contribute to the pathogenesis of PNS.

关键词： Familial Mediterranean fever   biomarkers   interleukin 18  

关键词： Hepatitis B virus   Kupffer cells   CD163   T cells   Antiviral immunity  

摘要： Background & aims: Chronic hepatitis B (CHB) arises from a persistent hepatitis B virus (HBV) infection, complicating efforts for a functional cure. Kupffer cells (KCs), liver-resident macrophages, are pivotal in mediating immune tolerance to HBV. Although CD163 marks M2-polarized KCs, its precise role in HBV infection remains unclear and warrants further investigation. Methods: CD163 expression in liver tissues of patients with CHB was analyzed using the Gene Expression Omnibus (GEO) database. Cd163 knockout mice were utilized to establish HBV-persistent mouse model, and CD163 deficiency effect on HBV viral markers and T cell immune responses were examined in vivo and in vitro. Results: CD163 expression was elevated and correlated with ALT levels in the liver of patients with CHB. In HBVpersistent mouse model, CD163 deficiency facilitated the clearance of HBsAg, HBeAg, HBV DNA, and HBcAg. Additionally, CD163 deficiency promoted the differentiation of na & iuml;ve T cells into HBV-specific effector T cells. Further, we found that CD163 deficiency reduces KCs-derived IL-10 secretion, and blocking IL-10 further strengthens the enhanced HBV-specific T cell response due to CD163 deficiency. Conclusions: Our findings indicate that CD163 deficiency enhances the HBV-specific T cell response, thereby facilitating HBV clearance through reducing KCs-derived IL-10 secretion. This suggests that CD163 may serve as a potential target for the restoration of exhausted T cell function.

关键词： Empagliflozin   SGLT-2 Inhibitors   Doxorubicin   PI3K/Akt/mTOR Pathway   Oxidative Stress   Neuroinflammation  

摘要： Chemobrain is a cognitive impairment observed in up to 75% of cancer patients treated with doxorubicin (DOX). Cognitive deficits associated with DOX are complex, and multiple interplay pathways contribute to memory impairment and the loss of concentration. Empagliflozin (EMPA), a sodium-glucose co-transporter-2 (SGLT-2) inhibitor with neuroprotective potential, has recently been elucidated because of its regulatory effects on oxidative stress and neuroinflammation. Thus, this study aimed to explore the protective mechanisms of EMPA in DOX-induced chemobrain. Rats were allocated to four groups: normal (NC), EMPA, DOX, and EMPA + DOX. Chemobrain was induced in the third and fourth groups by DOX (2 mg/kg, IP) on the 0th, 7th, 14th, and 21st days of the study, while EMPA was administered (10 mg/kg, PO) for 28 consecutive days in both the EMPA and EMPA + DOX groups. Behavioral and biochemical assessments were then performed. Rats treated with DOX exhibited significant memory, learning, and muscle coordination dysfunctions. Moreover, DOX boosted oxidative stress in the brain, as evidenced by elevated malondialdehyde (MDA) content together with decreased levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) and reduced glutathione (GSH). Neuroinflammation was also observed as an upsurge of tumor necrosis factor-alpha (TNF-alpha) and nuclear factor kappa B (NF-kappa B) (p65). Additionally, DOX diminished the expression of brain-derived neurotrophic factor (BDNF) and increased phosphoinositol-3-kinase (PI3K), phosphorylated-Akt (pAkt), and mammalian target of rapamycin (mTOR) content. EMPA exhibited potent neuroprotective potential in DOX-induced cognitive impairment, attributed to its antioxidant and neuroplasticity-enhancing properties and suppression of the PI3K/Akt/mTOR/NF-kappa B/TNF-alpha signaling *** AbstractDoxorubicin (DOX)-induced chemobrain may occur because of increased tumor necrosis factor-alpha (TNF-alpha) leve

关键词： COVID-19   IL-6   ferritin   C-reactive protein   cytokine storm   immuno-modulation   beta glucans   adjunct treatment  

摘要： BackgroundSeveral biomarkers, including C-reactive protein (CRP), ferritin, D-dimer, and Interleukin-6 (IL-6), are established predictors of disease severity and respiratory failure in patients with *** this randomised clinical study, we evaluated the efficiency of the combination of 2 variants' AFO-202 and N-163 strains of Aureobasidium pullulans produced 1,3-1,6 beta-glucans in comparison with the control arm on these biomarkers in COVID-19 *** RT-PCR positive COVID-19 patients were divided into 2 groups: control (n = 22) and standard treatment;ii. (n = 18) - Standard treatment + combination of AFO-202 and N-163 beta glucans for 15 ***-6 levels significantly decreased in the treatment group on day 7 (P = 0.03) but not by day 15 (P = 0.30). CRP levels in the treatment group decreased at day 7 (5.53 +/- 8.21 mg/L) compared to baseline but showed no significant difference from the control group (4.91 +/- 12.54 mg/L, P = 0.98). At day 15, CRP levels remained lower in the treatment group (5.42 +/- 10.41 mg/L) but increased in the control group (14.0 +/- 37.16 mg/L), with no significant difference (P = 0.52). Ferritin levels dropped significantly in the treatment group by day 15 (from 560.58 +/- 537.30 ng/mL to 127.51 +/- 215.91 ng/mL) but increased in the control (P = 0.98). D-dimer levels decreased in the treatment group by day 15 but were not significantly different from controls (P = 0.56).ConclusionThese results indicate that while co-supplementation with AFO-202 and N-163 beta-glucans led to improvement in CRP, ferritin, and IL-6 levels in COVID-19 patients, only the reduction in IL-6 levels on day 7 reached statistical significance. Further long-term multicentric clinical research is warranted to validate the potential of these supplements as treatment adjuncts, for addressing inflammation in COVID-19, especially in vulnerable populations infected with emerging SARS-CoV-2 variants.

关键词： ESRD   end-stage renal disease   Cr   creatinine   BMI   body mass index   CI   confidence interval   FSGS   focal segmental glomerulosclerosis   tHcy   serum homocysteine   CRP   C-reactive protein   eGFR   estimated glomerular filtration rate   IFTA-i   interstitial fibrosis/tubular atrophy and inflammation   HLA   human leukocyte antigen  

摘要： Background. Various clinicopathologic markers, such as 1-year serum creatinine (Cr), have been used to prognosticate kidney allografts after transplantation. However, a contemporary analysis of their relationship with long-term graft survival is lacking. This study aimed to analyze recent data on the association of prognostic factors with kidney allograft survival in patients who underwent transplantation in the modern era. Methods. Adult kidney-transplant recipients in the UNOS database (2008-2020) were identified. Living and deceased donor allografts were analyzed separately and stratified by 1-year serum Cr level: <= 1.0, 1.0 to 1.5, 1.5 to 2.0, and >2.0 mg/dL. Time-to-event analysis was performed with long-term death-censored graft survival as the primary outcome. In addition, factors associated with raised 1-year serum Cr and with long-term allograft failure were identified. Results. 174,547 patients were included. Ten-year survival decreased with increasing 1-year creatinine, and these trends persisted on adjusted analysis for both living donor (Cr <= 1.0 mg/dL: reference;Cr 1.0-1.5 mg/dL aHR = 1.77 [1.59-1.96];Cr 1.5-2.0 mg/dL aHR = 3.24 [2.89-3.64] and;Cr > 2.0 mg/dL aHR = 9.78, [8.64-11.07], P < .01) as well as deceased donor allografts (Cr <= 1.0 mg/dL: reference;Cr 1.0-1.5 mg/dL aHR = 1.74 [1.63-1.86];Cr 1.5-2.0 mg/dL aHR = 3.06 [2.84-3.30] and;Cr > 2.0 mg/dL aHR = 8.51, [7.89-9.18], P < .01). Conclusion. These results characterize the association between 1-year serum creatinine levels and other clinicopathologic factors with long-term kidney allograft survival. We demonstrate the ability of prognostic factors to stratify patients by risk of graft failure in a contemporary patient cohort that is representative of current practice and outcomes.

关键词： triterpenes of Prunella vulgaris (PVT)   triple-negative breast cancer   PTP1B/PI3K/AKT/mTOR pathway   IL-24/CXCL12/CXCR4 signaling axis  

摘要： Triple-negative breast cancer (TNBC) is a type of breast cancer characterized by high molecular heterogeneity. Owing to the lack of effective therapeutic strategies, patients with TNBC have a poor prognosis. Prunella vulgaris L. has the effects of reducing swelling, dissolving knots and treating breast carbuncles and mammary rocks. Modern pharmacological studies have reported that it can effectively inhibit the growth of breast cancer. The main active antitumor components of Prunella vulgaris are triterpenoids (PVT);however, the role and potential mechanism of PVT in TNBC remain unexplored. Our study aimed to further explore the inhibitory effects of PVT on TNBC and the associated mechanism. The results showed that 19 compounds associated with PVT were identified, 9 of which were triterpenoids. The percentages of ursolic acid and oleanolic acid in PVT were 34.51% and 11.32%, respectively. Triterpenes of Prunella vulgaris significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells and promoted their apoptosis in a concentration-dependent manner. PVT could also effectively downregulate the mRNA and protein expression levels of Ptp1b, Pi3k, Akt and mtor and upregulate the mRNA and protein expression levels of Il-24 in MDA-MB-231 cells. In mice with tumors of TNBC, PVT significantly reduced tumor growth and the expression levels of PTP1B, CXCL12, CXCR4, PI3K, AKT, mTOR and other proteins in TNBC tumor tissue and upregulated the expression of IL-24. This study showed that PVT played an anti-TNBC role by regulating the PTP1B/PI3K/AKT/mTOR signaling pathway and the IL-24/CXCL12/CXCR4 signaling axis.

关键词： Carbothioamide   X-ray diffraction   Thiazole   Cell cytotoxicity   Anti-inflammatory   Anti-oxidant   Molecular docking   MD simulation  

摘要： In this study, tetrahydronaphthalene carbothioamides 2, characterized by spectroscopic methods and X-ray diffraction studies, were used to develop a series of novel tetrahydronaphthalenone-coupled thiazole derivatives 3. The synthesized thiazole hybrids were evaluated for in-vitro anti-inflammatory activity against lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophage cells. Notably, compound 3f demonstrated the most potent anti-inflammatory effect by significantly reducing the expression of pro-inflammatory mediators, including nitric oxide species (IC50 = 62.93 mu M) and tumor necrosis factor-alpha (TNF-alpha) (67.50 mu M). Additionally, 3f inhibited cyclooxygenase-2 (COX-2) (IC50 = 73.18 mu M compared to celecoxib 41.21 mu M) expression in a dose-dependent manner. The antioxidant activity of newly generated derivatives was also assessed using the DPPH assay, with compounds 3a, 3b, and 3c showing the highest inhibition rates of 69.94%, 68.82%, and 64.77% at 100 mu g/mL, respectively. Molecular docking studies targeting the active site of Human Peroxiredoxin 5 (PDB ID: 1HD2) and COX-2 (PDB ID: 4M11) were conducted to explore the potential interactions of these compounds with the receptor. Molecular dynamics (MD) simulation predicted the stability of the protein-ligand complex.