Distinct adaptive immune receptor feature of adipose-derived mesenchymal stem cells (AD-MSCs) treatment of psoriasis.

Psoriasis (Ps) is one of the most common chronic inflammatory skin disorders with its pathogenesis correlated with dysregulated innate and adaptive system. Even though biological agents have advanced the treatment of psoriasis, however, there are huge limitations, like high adverse reactions and relapse rate. Therefore, it is of great interest in searching clinical resolutions with better safety and efficacy. In the current study, we utilized the adipose-derived mesenchymal stem cell (AD-MSCs) to treat moderate/severe cases of psoriasis in a single-arm clinical study. This AD-MSC treatment has proven to be clinically safe and effective. Interestingly, a trend of adaptome improvement, including increased diversity, elevated uCDR3s and decreased large clone after AD-MSC treatment in a short (2 weeks) and long (12 weeks) terms. In conclusion, allogenic AD-MSC treatment has shown a good safety and efficacy in treating Ps and can effectively improve the compromised adaptive immune system of Ps patients.

Quercetin alleviates kidney damage caused by mercury Chloride: The protective effects of quercetin on autophagy and inflammation were studied based on TRIM32/TLR4/LC3 pathway.

OBJECTIVE: Mercury is one of the heavy metal pollutants causing serious harm to human health. Quercetin was observed to repair kidney damage through the TLR4/TRIM32 pathway, and the detoxification effect of quercetin on heavy metal poisoning was observed. METHODS: For the study, the researchers divided 40 male mice from the KM strain into five groups: control, HgCl2, QU30, HgCl2+QU15, and HgCl2+QU30. The biological effects of those mice in each group were detected by the biochemical experiment, histopathology experiment and protein expression experiment respectively. RESULTS: HgCl2 had effects in increasing the level of malondialdehyde (MDA) and decreasing the activity of antioxidant enzymes (P < 0.05). HgCl2 induced inflammation by increasing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and Toll Like Receptor 4 (TLR-4) (P < 0.05). The expression of creatinine (CRE) and urea nitrogen (BUN) showed that HgCl2 promoted kidney injury. HgCl2 altered renal tissue integrity and TRIM32 expression which resulted in the increased autophagy associated protein levels of LC3. In contrast, quercetin reduced oxidative stress, autophagy, inflammation and histopathological changes (P < 0.05). CONCLUSION: Quercetin has the renal protection effects of anti-inflammation, anti-oxidation and anti-autophagy.

Efficacy and Safety of 5-Aminolevulinic Acid Photodynamic Therapy for Treating Cervical and Vaginal Intraepithelial Neoplasia.

Persistent HPV infections may cause cervical and vaginal intraepithelial neoplasia (CIN and VaIN). Traditional methods might destroy the structure and function of the cervix. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive targeted therapy. This study aims to evaluate the efficacy and safety of ALA-PDT for CIN and VaIN and the clearance of HPV. A retrospective study of 303 patients who confirmed CIN or VaIN and received ALA-PDT was conducted. All the patients were followed up at six and twelve months after treatment and then annually thereafter. The effect was evaluated through HPV genotyping, a cytology test, and colposcopy-directed biopsy if necessary. After ALA-PDT, the remission rates for CIN 2, CIN 3, VaIN 2, and VaIN 3 were 90.6%, 88.5%, 87.3%, and 77.8%. For CIN 1, the remission rate at the six-month follow-up was 93.1%. The total HPV clearance rates were 72.5% at the six-month follow-up and 85.7% at the 12-month follow-up. The most common adverse event was vaginal discharge. No severe adverse effect was observed. ALA-PDT is an effective and safe treatment for all grades of CIN and VaIN and is helpful in clearing HPV with minimal side effects. This treatment may not influence fertility and delivery.

Anlotinib may enhance the efficacy of anti-PD1 therapy by inhibiting the AKT pathway and promoting the apoptosis of CAFs in lung adenocarcinoma.

Although PD-1 inhibitors have revolutionized the treatment paradigm of non-small cell lung cancer (NSCLC), their efficacy in treating NSCLC has remained unsatisfactory. Targeting cancer-associated fibroblasts (CAFs) is a potential approach for improving the immunotherapy response. Multitarget antiangiogenic tyrosine kinase receptor inhibitors (TKIs) can enhance the efficacy of PD-1 inhibitors in NSCLC patients. However, the effects and mechanisms of antiangiogenic TKIs on CAFs have not been elucidated. In this study, we first compared anlotinib with other antiangiogenic TKIs and confirmed the superior efficacy of anlotinib. Furthermore, we established NSCLC-associated CAF models and found that anlotinib impaired CAF viability and migration capacity and contributed to CAF apoptosis and cell cycle arrest in the G2/M phase. Moreover, anlotinib treatment attenuated the capacity of CAFs to recruit lung cancer cells and macrophages. Experiments in animal models suggested that anlotinib could enhance the efficacy of anti-PD1 therapy in NSCLC and affect CAF proliferation and apoptosis. Anlotinib increased the abundance of tumor-infiltrating CD8 + T cells, and PD-1 inhibitor-induced cytotoxicity to tumor cells was achieved through the transformation of the tumor microenvironment (TME) caused by anlotinib, which may partly explain the synergistic antitumor effect of anlotinib and PD-1 inhibitors. Mechanistically, anlotinib affects CAF apoptosis and cell viability at least in part by inhibiting the AKT pathway. In conclusion, our study suggested that anlotinib could regulate the TME, inhibit the AKT pathway and promote CAF apoptosis, providing new insights into the antitumor effect of anlotinib and improving the efficacy of immunotherapy.

Decompressive craniectomy for patients with malignant infarction of the middle cerebral artery: A pooled analysis of two randomized controlled trials.

BACKGROUND: Decompressive craniectomy (DC) reduces mortality without increasing the risk of very severe disability among patients with life-threatening massive cerebral infarction. However, its efficacy was demonstrated before the era of endovascular thrombectomy trials. It remains uncertain whether DC improves the prognosis of patients with malignant middle cerebral artery (MCA) infarction receiving endovascular therapy. METHODS: We pooled data from two trials (DEVT and RESCUE BT studies in China) and patients with malignant MCA infarction were included to assess outcomes and heterogeneity of DC therapy effect. Patients with herniation were dichotomized into DC and conservative groups according to their treatment strategy. The primary outcome was the rate of mortality at 90 days. Secondary outcomes included disability level at 90 days as measured by the modified Rankin Scale score (mRS) and quality-of-life score. The associations of DC with clinical outcomes were performed using multivariable logistic regression. RESULTS: Of 98 patients with herniation, 37 received DC surgery and 61 received conservative treatment. The median (interquartile range) was 70 (62-76) years and 40.8% of the patients were women. The mortality rate at 90 days was 59.5% in the DC group compared with 85.2% in the conservative group (adjusted odds ratio, 0.31 [95% confidence interval (CI), 0.10-0.94]; P=0.04). There were 21.6% of patients in the DC group and 6.6% in the conservative group who had a mRS score of 4 (moderately severe disability); and 10.8% and 4.9%, respectively, had a score of 5 (severe disability). The quality-of-life score was higher in the DC group (0.00 [0.00-0.14] vs 0.00 [0.00-0.00], P=0.004), but DC treatment was not associated with better quality-of-life score in multivariable analyses (adjusted ß Coefficient, 0.02 [95% CI, -0.08-0.11]; p=0.75). CONCLUSIONS: DC was associated with decreased mortality among patients with malignant MCA infarction who received endovascular therapy. The majority of survivors remained moderately severe disability and required improvement on quality of life. CLINICAL TRIAL REGISTRATION: The DEVT trial: http://www.chictr.org. Identifier, ChiCTR-IOR-17013568. The RESCUE BT trial: URL: http://www.chictr.org. Identifier, ChiCTR-INR-17014167.

Self-Assembled DNA Composite-Engineered Mesenchymal Stem Cells for Improved Skin-Wound Repair.

The direct use of mesenchymal stem cells (MSCs) as therapeutics for skin injuries is a promising approach, yet it still faces several obstacles, including limited adhesion, retention, and engraftment of stem cells in the wound area, as well as impaired regenerative and healing functions. Here, DNA-based self-assembled composites are reported that can aid the adhesion of MSCs in skin wounds, enhance MSC viability, and accelerate wound closure and re-epithelialization. Rolling-circle amplification (RCA)-derived DNA flowers, equipped with multiple copies of cyclic Arg-Gly-Asp (cRGD) peptides and anti-von Willebrand factor (vWF) aptamers, act as robust scavengers of reactive oxygen species (ROS) and enable synergistic recognition and adhesion to stem cells and damaged vascular endothelial cells. These DNA structure-aided stem cells are retained at localized wound sites, maintain repair function, and promote angiogenesis and growth factor secretion. In both normal and diabetes-prone db/db mice models with excisional skin injuries, facile topical administration of DNA flower-MSCs elicits rapid blood vessel formation and enhances the sealing of the wound edges in a single dose. DNA composite-engineered stem cells warrant further exploration as a new strategy for the treatment of skin and tissue damage.