Zhen-Wu-Tang ameliorates lupus nephritis by diminishing renal tissue-resident memory CD8+ T cells via suppressing IL-15/STAT3 pathway.

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-ß. 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-ß in vitro. Mechanistically, it suppressed phosphorylation of STAT3 and CD122 （IL2/IL-15Rß）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.

MiR-124-3p mediates gastric cancer cell ferroptosis induced by an anti-cancer drug polyphyllin I.

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.

The protective effect of harpagoside on angiotensin II (Ang II)-induced blood-brain barrier leakage in vitro.

Hypertension and its associated dysfunction of the blood-brain barrier (BBB) contribute to cerebral small vessel disease (cSVD). Angiotensin II (Ang II), a vasoactive peptide of the renin-angiotensin system (RAS), is not only a pivotal molecular signal in hypertension but also causes BBB leakage, cSVD, and cognitive impair. Harpagoside, the major bioactive constituent of Scrophulariae Radix, has been commonly used for the treatment of multiple diseases including hypertension in China. The effect of harpagoside on Ang II-induced BBB damage is unclear. We employed an immortalized endothelial cell line (bEnd.3) to mimic a BBB monolayer model in vitro and investigated the effect of harpagoside on BBB and found that harpagoside alleviated Ang II-induced BBB destruction, inhibited Ang II-associated cytotoxicity in a concentration-dependent manner and attenuated Ang II-induced reactive oxygen species (ROS) impair by downregulation of Nox2, Nox4, and COX-2. Harpagoside prevented Ang II-induced apoptosis via keeping Bax/Bcl-2 balance, decreasing cytochrome c release, and inactivation of caspase-8, caspase-9, and caspase-3 (the mitochondria-dependent and death receptor-mediated apoptosis pathways). Moreover, harpagoside can alleviate Ang II-induced BBB damage through upregulation of tight junction proteins and decrease of caveolae-mediated endocytosis. Thus, harpagoside might be a potential drug to treat Ang II-induced cSVD.

Clinical features of retinal diseases masquerading as retrobulbar optic neuritis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Managements of optic neuritis (ON) included high-dose corticosteroids or combined with systemic immunomodulatory agents. It was important to make a correct diagnosis of ON before initiation of treatment. The purpose of the study was to report and analyze the clinical features of retinal diseases in patients who were misdiagnosed as having retrobulbar ON.</p><p><b>METHODS</b>Retrospective review of 26 patients (38 eyes) initially diagnosed with retrobulbar ON but were ultimately diagnosed with retinal or macular diseases. Data obtained from fundus examination, fluorescence fundus angiography (FFA), automated static perimetry, full-field electroretinogram (ffERG), multifocal electroretinogram (mfERG), and optical coherence tomography (OCT) were evaluated.</p><p><b>RESULTS</b>Thirty-eight eyes of 26 patients were found to have misdiagnosis of retrobulbar ON, based on normal or slight abnormal fundus findings and abnormal visual evoked potentials (VEP). The mean age of the patients was 34 years and the correct diagnosis of the patients included acute zonal occult outer retinopathy (AZOOR, 15 eyes, 14 patients), occult macular dystrophy (OMD, 8 eyes, 4 patients), cone or cone-rod dystrophy (10 eyes, 5 patients), acute macular neuroretinopathy (AMNR, 3 eyes, 2 patients), and cancer-associated retinopathy (CAR, 2 eyes, 1 patient).</p><p><b>CONCLUSION</b>When attempting to diagnose retrobulbar ON in clinical practice, it is crucial to carry out necessary examinations of the retinal function and morphology to decrease misdiagnosis.</p>

[Pharmacognosy identification of Embelia parviflora].

OBJECTIVE: To study the morphological character and microscopic identification of Embelia parviflora. METHODS: Researches on the morphological character and microscopic identification of roots and stems of Embelia parviflora were carried on respectively. RESULTS: Significant microscopic characteristics of Embelia parviflora were confirmed. Such as single stone cells scattered in the root cortical, lots of stone cell groups and fiber bundles scattered in the column parts and became ring intermittently. Stem phloem was broad, large scale secretory cells scattered near cambium region and stone cell groups in ray parts. Crystal stone cells of thick and thin could be seen in powder. CONCLUSION: These features can be used as the reference for quality standard of Embelia parviflora.

Genotyping and CA4 gene analysis in a Chinese family with retinitis pigmentosa / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To illuminate pathogenic gene and mutation in a Chinese family with autosomal dominant retinitis pigmentosa (adRP).</p><p><b>METHODS</b>Genetic linkage analysis was performed on the known genetic loci for adRP with a panel of polymorphic markers, and then all exons including exon-intron boundary, 5oUTR and 3oUTR of the candidate gene were sequenced directly.</p><p><b>RESULTS</b>Two-point LOD scores were negative with all markers tested except D17S701 (Zmax=2.107, theta=0) and D17S1604 (Zmax=1.806, theta=0). The disease gene locus was confined to RP17 with further genetic linkage and haplotype analysis. Screening all exons including exon-intron boundary, 5oUTR and 3oUTR of carbonic anhydrase 4 (CA4) revealed no mutation in this family.</p><p><b>CONCLUSION</b>The disease-causing gene of one Chinese family with adRP was first mapped to RP17, however no gene mutation of CA4 was detected in this family. Maybe there is a complex CA4 gene mutation in this family or a new disease-causing gene for this family in this locus, further study need to be done.</p>