Treatment of berberine alleviates diabetic nephropathy by reducing iron overload and inhibiting oxidative stress

Diabetic nephropathy (DN) has become one of the major fatal factors in diabetic patients. The aim of this study was to elucidate the function and mechanism by which berberine exerts renoprotective effects in DN. In this work, we first demonstrated that urinary iron concentration, serum ferritin and hepcidin levels were increased and total antioxidant capacity was significantly decreased in DN rats, while these changes could be partially reversed by berberine treatment. Berberine treatment also alleviated DN-induced changes in the expression of proteins involved in iron transport or iron uptake. In addition, berberine treatment also partially blocked the expression of renal fibrosis markers induced by DN, including MMP2, MMP9, TIMP3, β-arrestin-1, and TGF-β1. In conclusion, the results of this study suggest that berberine may exert renoprotective effects by ameliorating iron overload and oxidative stress and reducing D

Relation between sleep disorders and post-stroke cognitive impairment

ObjectiveTo investigate the effects of sleep disorders on post-stroke cognitive impairment (PSCI) and other factors affecting post-stroke cognitive impairment.MethodsA total of 1,542 first-ever stroke inpatients in department of neurology of Tianjin Huanhu Hospital from 2015.6.1 to 2016.12.31. We recorded the personal history of patients. The MMSE (mini-mental state examination), MoCA (Montreal Cognitive Assessment), HAMD (Hamilton Depression Scale), BI (Barthel index), mRS (Modified Rankin Scale), PSQI (Pittsburgh Sleep Quality Index), ESS (Epworth Sleepiness Scale), Berlin questionnaire, nocturnal TST (total sleep time) were assessed before discharge. All patients were followed up at 3 months, 6 months, and 4 years (2019–2020) after stroke. During follow-up, the above scales should be evaluated again to assess the sleep status and cognitive function of patients at that time.ResultsNocturnal TST (>8 h) (OR 3.540, 95% CI 1.692–7.406, P = 0.001) was a risk factor for cognitive impairment 3 months after stroke. Nocturnal TST (<7 h) (OR 6.504, 95% CI 3.404–12.427, P < 0.001) was a risk factor for cognitive impairment 6 months after stroke. Low sleep quality (OR 2.079, 95% CI 1.177–3.672, P = 0.012), sleepiness (OR 3.988, 95% CI 1.804–8.818, P = 0.001), nocturnal TST (<7 h) (OR 11.334, 95% CI 6.365–20.183, P < 0.001), nocturnal TST (>8 h) (OR 4.096, 95% CI 1.682–9.975, P = 0.002) were risk factors for cognitive impairment 4 years after stroke. The prevalence of cognitive impairment with TIA were 79.3% at admission, 68.1% at 3-months follow-up, 62.1% at 6-months follow-up and 52.2% at 4-year follow-up.ConclusionLong or short nocturnal TST (<7 h or >8 h) was a risk factor for cognitive impairment after stroke (3 months, 6 months and 4 years). Poor sleep quality and sleepiness were shown to be risk factors for cognitive impairment at 4-year follow-up. Cognitive impairment was very common in patients with TIA

Segmental Membranous Glomerulopathy in Adults

Introduction: The clinicopathological features of segmental membranous glomerulopathy (SMGN) have not been well characterized. The aim of this study was to investigate the prevalence and clinicopathological features of SMGN in adults. Methods: Adult patients with biopsy-confirmed SMGN in the native kidney at our center between January 2017 to September 2020 were identified. The clinicopathological features of SMGN were collected. The glomerular deposition of IgG subclasses, M-type phospholipase A2 receptor 1 (PLA2R), thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) were tested. Clinical and pathologic features were comparable between NELL1-positive and NELL1-negative SMGN. Results: A total of 167 patients with biopsy-proven SMGN were enrolled. During the same period, 32,640 (33.0%) out of 98,939 renal biopsies were diagnosed with membranous nephropathy (MN) in adults. SMGN accounted for 0.17% of total kidney biopsies and 0.51% of MN in adults. One hundred and fifty (89.8%) cases were isolated SMGN and 17 (10.2%) cases were complicated with other kidney disease. Clinically, the median age of isolated SMGN patients was 41.5 years, with female (74%) predominance, and 33.1% had full nephrotic syndrome. Pathologically, IgG1 was the dominant subclass (92.5%), followed by IgG4 (45.0%). PLA2R and THSD7A staining were done in 142 and 136 isolated SMGN cases, respectively. In which, all the cases showed negative. NELL1 staining was done in 135 isolated SMGN cases, 58 cases (43.0%) showed positive. Fifty-eight patients (41.1%) had diffuse (≥90%) foot process effacement, 119 patients (83.8%) had either stage I (38.0%) or stage II (45.8%) membranous alterations in patients with SMGN. Most patients with NELL1-positive SMGN were female. Patients with NELL1-positive SMGN were more likely with lower prevalence of full nephrotic syndrome than NELL1-negative SMGN. Conclusions: SMGN is a relatively rare pathological type. Majority of patients with isolated SMGN were female, with a median age of 41.5 years, 33.1% had full nephrotic syndrome, absence of PLA2R and THSD7A, 43.0% with NELL1-positive, and mainly stage I or II MN (83.8%). NELL1 is the major target antigen of SMGN in adults

Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients

IntroductionThe SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required.MethodsWe have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. ResultsThe aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. DiscussionOur findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278

Modification of Silica Xerogels with Polydopamine for Lipase B from <i>Candida antarctica</i> Immobilization

Silica xerogels have been proposed as a potential support to immobilize enzymes. Improving xerogels’ interactions with such enzymes and their mechanical strengths is critical to their practical applications. Herein, based on the mussel-inspired chemistry, we demonstrated a simple and highly effective strategy for stabilizing enzymes embedded inside silica xerogels by a polydopamine (PDA) coating through in-situ polymerization. The modified silica xerogels were characterized by scanning and transmission electron microscopy, Fourier tranform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and pore structure analyses. When the PDA-modified silica xerogels were used to immobilize enzymes of Candida antarctica lipase B (CALB), they exhibited a high loading ability of 45.6 mg/gsupport, which was higher than that of immobilized CALB in silica xerogels (28.5 mg/gsupport). The immobilized CALB of the PDA-modified silica xerogels retained 71.4% of their initial activities after 90 days of storage, whereas the free CALB retained only 30.2%. Moreover, compared with the immobilization of enzymes in silica xerogels, the mechanical properties, thermal stability and reusability of enzymes immobilized in PDA-modified silica xerogels were also improved significantly. These advantages indicate that the new hybrid material can be used as a low-cost and effective immobilized-enzyme support

The ATR inhibitor VE-821 increases the sensitivity of gastric cancer cells to cisplatin

Background: Chemoresistance is a common event after cancer chemotherapy, including gastric cancer (GC). Cisplatin has been reported to induce the DNA damage response (DDR), thus leading to chemoresistance. VE-821, a specific inhibitor of ATR, has been proven to suppress a variety of solid malignancies effectively. Our study aimed to explore the effect of VE-821 on enhancing the chemical sensitivity to cisplatin and clarify the potential molecular mechanisms. Methods: Cell viability and apoptosis of MKN-45 and AGS were measured by CCK8 and flow cytometry assay respectively. Western blotting was used to detect the expression of target proteins. TCGA database was used to analyze the correlation between the ATR expression with the prognosis of GC patients. The viability of GC organoids was detected by Cell Titer Glo (CTG) through luminescence. Results: Cisplatin inhibited the proliferation and induced apoptosis of GC cells with a relatively high IC50 value, and increased the phosphorylation levels of ATR-CHK1 and H2AX. VE-821 achieved the same effects but by downregulating the phosphorylation levels of the ATR-CHK1 pathway. Besides, higher ATR expression in GC tissues was positively correlated with higher pathological stage in GC patients. Interestingly, ATR inhibition reversed cisplatin-induced STAT3 activation and enhanced H2AX levels. Moreover, VE-821 significantly sensitized GC cells to cisplatin, and these two drugs had synergistic effects in GC cell lines, organoids, and in vivo. Conclusion: Our results suggested VE-821 sensitized GC cells to cisplatin via reversing DDR activation. And VE-821 treatment may be a promising therapeutic strategy for GC patients with cisplatin resistance