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Zhen-Wu-Tang (ZWT), a conventional herbal mixture, has been recommended for treating lupus nephritis (LN) in clinic. However, its mechanisms of action remain unknown. Here we aimed to define the immunological mechanisms underlying the effects of ZWT on LN and to determine whether it affects renal tissue-resident memory T (TRM) cells. Murine LN was induced by a single injection of pristane, while in vitro TRM cells differentiated with IL-15/TGF-β. We found that ZWT or mycophenolate mofetil treatment significantly ameliorated kidney injury in LN mice by decreasing 24-h urine protein, Scr and anti-dsDNA Ab. ZWT also improved renal pathology and decreased IgG and C3 depositions. In addition, ZWT down-regulated renal Desmin expression. Moreover, it lowered the numbers of CD8+ TRM cells in kidney of mice with LN while decreasing their expression of TNF-α and IFN-γ. Consistent with in vivo results, ZWT-containing serum inhibited TRM cell differentiation induced by IL-15/TGF-β in vitro. Mechanistically, it suppressed phosphorylation of STAT3 and CD122 （IL2/IL-15Rβ）expression in CD8+ TRM cells. Importantly, ZWT reduced the number of total F4/80+CD11b+ and CD86+, but not CD206+, macrophages in the kidney of LN mice. Interestingly, ZWT suppressed IL-15 protein expression in macrophages in vivo and in vitro. Thus, we have provided the first evidence that ZWT decoction can be used to improve the outcome of LN by reducing CD8+ TRM cells via inhibition of IL-15/IL-15R /STAT3 signaling.

Background: Alzheimer's disease (AD) is an age-related neurodegenerative disease, which manifests primarily as memory impairment accompanied by a gradual decline in cognitive function. Rehmanniae Radix Praeparata (RRP) is a traditional Chinese medicine herb, which is widely used clinically and has diverse pharmacological properties. However, the protective properties and the underlying mechanisms by which RRP counteracts oxidative stress to treat AD have not been elucidated. Methods: In the study, we explored the neuroprotective impact of RRP on mitigating oxidative stress damage using C. elegans and Aβ1-42-induced HT22 cells. In the study encompassing the use of HT22 cells, we detected cell viability, ROS level, MDA/T-AOC/CAT/SOD activity, HT22 cells apoptosis and Nrf2 translocation. Western blot analysis was used to examine changes in protein expression levels. In nematode experiments, we performed spawning assay, life-span assay, ROS level, MDA/T-AOC/CAT/SOD activity, chemotaxis assay, paralysis, serotonin sensitivity, Th S Staining, acridine orange assay, SKN-1 nuclear localization and the gst-4 expression. Results: Pretreatment of RRP significantly reduced the generation of ROS and MDA in Aβ1-42-induced HT22 cells, and increase the T-AOC, CAT and total SOD activity. RRP mitigated the toxic effect and apoptosis induced by Aβ1-42 treatment, as evident by reduced cytochrome C release and decreased ratio of cleaved caspase-9/caspase-9, BAX/Bcl-2 and cleaved caspase-3/caspase-3. Additionally, RRP was found to induce Nrf2 nuclear translocation, elevate the expression of Nrf2 protein in the nucleus, and promote the expression of NQO1 and HO-1 proteins. In terms of the nematode experiments, RRP could prolong the survival time of N2 nematodes and improve the resistance of nematodes to external stress. RRP improved chemotaxis to chemical substances and decreased the sensitivity to 5-HT was observed in the CL2355 nematodes. It also alleviated the paralysis process and reduce Aβ deposition in the pharynx of the CL4176 nematodes. RRP inhibited the production of ROS and MDA, and increased the activity of T-AOC, CAT and total SOD in the nematodes. RRP decreased apoptosis in N2 C. elegans. Together, the data demonstrated that RRP possesses antioxidant capacity by promoting SKN-1 nuclear translocation and GST-4 expression in C. elegans. Conclusion: Overall, our study suggested that the antioxidant effect of RRP might occur by regulation of Nrf2/ARE pathway in HT22 cells, and is relevant to the activation of SKN-1 in C. elegans.

Background: Ferroptosis is an emerging type of regulated cell death and associated with antitumoral therapy, while some microRNAs have been shown to regulate the tumorigenesis and cancer progression. Meanwhile, polyphyllin I (PPI) has exhibited antitumoral effects by promoting cancer cell apoptosis and ferroptosis. However, it is unclear whether PPI induces cancer cell ferroptosis by regulating microRNAs.Methods: We used two gastric cancer cell lines (AGS and MKN-45) to set up a tumor model of the nude mice, which were then treated daily with PPI to measure the cancer growth in vitro and in vivo. Ferroptosis was measured using immunofluorescence staining and flow cytometric analysis according to levels of intracellular ROS, lipid ROS and ferrous ions. Moreover, NRF2 expression was measured by Western blotting. In some experiments, the mimics or inhibitors of miR-124-3p were used to further confirm its involvement in PPI-induced cancer cell ferroptosis.Results: Here we found that miR-124-3p mediated cancer ferroptosis and tumor repression induced by PPI since PPI increased miR-124-3p expression in gastric cancer cells and promoted their ferroptosis, whereas inhibition of miR-124-3p mostly abolished the effects of PPI on tumor growth, ferroptosis and NRF2 expression. Moreover, miR-124-3p mimics promoted cancer cell ferroptosis by downregulating NRF2 through directly targeting 3′-UTR region of NRF2, confirming a role for miR-124-3p in regulating PPI-induced ferroptosis.Conclusion: PPI exerts its antitumoral effects on the gastric cancer by promoting cell ferroptosis via regulating miR-124-3p. Our findings have clinical implications for cancer chemotherapy.

Multiple factors determine the susceptibility to intrauterine hepatitis B virus (HBV) infection. These factors include the HBV structure, HBV mutation, HBV DNA level, placental barrier, the immune status of the mother, and the genetic make-ups of the newborn infants. Since HLA system is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes are the key determinants of intrauterine HBV infection. In this study, we selected newborn infants of HBsAg-positive mothers, and divided the infants into 2 groups: intrauterine infection group and non-intrauterine infection group according to the status whether or not they were infected at birth. Each infected infant was compared with 2 controls from the same birth cohort. HLA-DR allele typing was performed using a PCR-sequence specific primer (PCR-SSP) for 24 subjects with intrauterine infection and 48 controls without infection. We found that, among the fifteen (15) HLA-DR alleles assessed, HLA-DRB1*07 was the one, and the only one, significantly in excess (OR = 6.66, P = 0.004) in the intrauterine infection group compared to the non-intrauterine infection group. Our findings thus suggest that high frequency of HLA class II molecules, e.g. HLA-DRB1*07, is associated with the susceptibility of the infants to intrauterine HBV infection.

Objective: To investigate whether the plasma asymmetrical dimethylarginine (ADMA) level correlates with the extent and severity of coronary atherosclerosis., Methods: 110 consecutive patients undergoing coronary angiography were divided into five groups according to the result thereof: control group (n = 22, with normal coronary artery), mild coronary artery disease (CAD) group (n = 21, with stenosis < 50% of the major coronary arteries), single branch CAD group III (n = 22, with stenosis >/= 50% of one major coronary artery); double branch CAD group IV (n = 23, with stenosis >/= 50% of two major coronary arteries); and multi-branch CAD group (n = 22, with significant stenosis >/= 50% of more than two major coronary arteries or companies with stenosis of left major coronary). ELISA was used to detect the plasma ADMA. Nitric acid reductase method and colorimetry were used to measure the levels of plasma nitric oxide (NO) and nitrogen oxide synthase (NOS). The relationship between the plasma ADMA and severity of CAD was analyzed., Results: The plasma ADMA levels of in last three a groups were 1.52 micromol/L +/- 0.61 micromol/L, 1.67 micromol/L +/- 0.80 micromol/L, and 2.60 micromol/L +/- 0.62 micromol/L all significantly higher than that of the control group (0.79 micromol/L +/- 0.54 micromol/L, P < 0.01). The plasma NO and NOS levels of the multi-branch CAD group were significantly lower than those of the other groups (all P < 0.01), and there were not significant differences in Plasma NO and NOS levels among the other groups. Multivariate stepwise logistic regression analysis showed that the plasma ADMA level was significantly positively correlated with the severity of coronary atherosclerosis (r = 0.684, P = 0.007) and total cholesterol and triglyceride (r = 0.623 and 0.536 respectively), and significantly negatively correlated with the NO and NOS levels (r = -0.709 and -0.701 respectively)., Conclusion: Correlated significantly with the severity of coronary atherosclerosis, the plasma ADMA level may become a novel marker of CAD.

Objective: To investigate the relationship between the levels of lysophsophatidic acid (LPA) and function of left ventricular after acute myocardial infarction (AMI) and the role of LPA in ventricular remodeling and the potential mechanism., Methods: In this study, we selected 86 patients with AMI and measured the levels of LPA and type III procollagen (PCIII) on admission and 4 day after admission, and performed echocardiographic examinations on admission and 8 approximately 10 day after admission. And according to their serum LPA value at day 4 patients were stratified into two group (group A, LPA < 6.0 micro mol/L, n = 45; group B, LPA >/= 6.0 micro mol/L, n = 41). In 40 normal individuals, level of LPA and PCIII were measured., Results: (1) The patient's levels of LPA after AMI were increased (5.1 micro mol/L +/- 1.1 micro mol/L and 6.4 micro mol/L +/- 1.3 micro mol/L vs 2.5 micro mol/L +/- 1.1 micro mol/L, P = 0.0001). (2) PCIII was significantly higher in group B than that in group A (136 micro g/L +/- 10 micro g/L vs 113 micro g/L +/- 12 micro g/L, P < 0.05). Left ventricular end-diastolic diameter was significantly higher in group B than in group A (54.0 mm +/- 3.3 mm vs 51.1 mm +/- 2.7 mm, P < 0.05). (3) The elevation of LPA after AMI was closed related to the function of left ventricular (P < 0.05)., Conclusion: The levels of LPA after AMI were increased, which may play a role in ventricular remodeling. The potential mechanism may be that LPA can stimulate cardiac myocyte hypertrophy and cardiac fibroblast proliferation and cause collagen production increasing.