Acupuncture on the Endometrial Morphology, the Serum Estradiol and Progesterone Levels, and the Expression of Endometrial Leukaemia-inhibitor Factor and Osteopontin in Rats

Although it is well known that acupuncture has beneficial effects on a variety of medical conditions especially in pain relief, nausea, and vomiting, it remains controversial whether it has positive impact on the female reproduction. The present study aimed to evaluate whether the following endometrial receptivity factors: the endometrial morphology, the hormone concentrations, and the protein expression of endometrial leukaemia-inhibitory factor (LIF) and osteopontin (OPN) could be improved by the acupuncture in clomiphene citrate(CC)-induced rat model during implantation period. Results showed that, compared with the CC group, glandular development advanced, the serum estradiol levels decreased significantly, and the glandular area and endometrial LIF and OPN expression were significantly higher in acupuncture group. There were no significant differences in serum progesterone levels, endometrial thickness, and stromal area between groups. These results suggest that acupuncture can improve certain aspects of endometrial receptivity in CC-induced rat model during implantation period, which might result in endometrial state better to female reproduction

Machine learning and integrative analysis identify the common pathogenesis of azoospermia complicated with COVID-19

BackgroundAlthough more recent evidence has indicated COVID-19 is prone to azoospermia, the common molecular mechanism of its occurrence remains to be elucidated. The aim of the present study is to further investigate the mechanism of this complication.MethodsTo discover the common differentially expressed genes (DEGs) and pathways of azoospermia and COVID-19, integrated weighted co-expression network (WGCNA), multiple machine learning analyses, and single-cell RNA-sequencing (scRNA-seq) were performed.ResultsTherefore, we screened two key network modules in the obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) samples. The differentially expressed genes were mainly related to the immune system and infectious virus diseases. We then used multiple machine learning methods to detect biomarkers that differentiated OA from NOA. Enrichment analysis showed that azoospermia patients and COVID-19 patients shared a common IL-17 signaling pathway. In addition, GLO1, GPR135, DYNLL2, and EPB41L3 were identified as significant hub genes in these two diseases. Screening of two different molecular subtypes revealed that azoospermia-related genes were associated with clinicopathological characteristics of age, hospital-free-days, ventilator-free-days, charlson score, and d-dimer of patients with COVID-19 (P < 0.05). Finally, we used the Xsum method to predict potential drugs and single-cell sequencing data to further characterize whether azoospermia-related genes could validate the biological patterns of impaired spermatogenesis in cryptozoospermia patients.ConclusionOur study performs a comprehensive and integrated bioinformatics analysis of azoospermia and COVID-19. These hub genes and common pathways may provide new insights for further mechanism research

Hub gene associated with prognosis in bladder cancer is a novel therapeutic target

Objective Bladder cancer is a clinical and social conundrum due to its high incidence and recurrence rate. It is urgent to find new targets for the diagnosis and treatment of bladder cancer and improve the prognosis and survival rate of bladder cancer patients. We sought a prognosis-related gene, built related models of evaluated bladder cancer and identified the function of the hub gene in bladder cancer. Methods We downloaded the data of bladder cancer patients from the TCGA database, and used differentially expressed genes (DEGs), copy number variation (CNV) and survival analysis to scan the hub genes associated with prognosis in bladder cancer. Then, multi-factor cox regression was used to obtain the bladder cancer prognosis correlation model. Then, we analyzed the relationship between the expression of hub gene and immune microenvironment of bladder cancer. The relationship between the expression of hub gene and prognosis in bladder cancer patients was verified by immunohistochemistry. Cell proliferation assay and drug sensitivity test in vivo were used to verify the inhibition of bladder cancer by targeted inhibitors. Results In bladder cancer, we screened seven hub genes (ACLY, CNP, NKIRAS2, P3H4, PDIA6, VPS25 and XPO1) associated with survival. Moreover, the multifactor regression model constructed with hub gene can well distinguish the prognosis of bladder cancer. Hub gene is mostly associated with immune microenvironment. Immunohistochemical results basically confirmed the importance of XPO1 in bladder cancer. Selinexor (an inhibitor of XPO1) could effectively inhibit the proliferation of bladder cancer in the cell proliferation experiments by CCK-8 assays and it could suppress the growth of bladder cancer in mouse bladder cancer model. Conclusions In this study, a prognostic model with seven hub genes has provided great help for the prognosis prediction of bladder cancer patients. And XPO1 is an important target affecting the prognosis of bladder cancer, and inhibition of XPO1 can effectively inhibit bladder cancer proliferation and growth

A new bivalve fauna from the Permian-Triassic boundary section of southwestern China

A new marine bivalve fauna from the continuous Upper Permian Longtan Formation to Lower Triassic Yelang Formation of the Zhongzai section in southwestern China is documented. Four bivalve assemblages spanning the Permian–Triassic boundary are recognized and regionally correlated in South China. The bivalve assemblages changed from elements dominated by Palaeozoic types to those dominated by Mesozoic types. Three new species, Claraia zhongzaiensis sp. nov., Claraia sp. nov. 1 and Claraia sp. nov. 2, are described

Baicalin reduces sunitinib-induced cardiotoxicity in renal carcinoma PDX model by inhibiting myocardial injury, apoptosis and fibrosis

Background and purpose: Sunitinib, a multi-targeted tyrosine kinase inhibitor, has anticancer function but it’s clinical use is often limited by cardiovascular complications. Baicalin is a flavonoid extracted from radix scutellariae that has been demonstrated various pharmacological activities including anti-inflammatory property, but its potential effects in sunitinib -induced cardiotoxicity have not been clarified. In this study, we to investigate the effect of baicalin in sunitinib-induced cardiotoxicity in vivo by using patient-derived xenograft (PDX) model. Material and Methods: Female Nod Scid mice with PDX were treated with vehicle, sunitinib (50 mg/kg/d), baicalin (100 mg/kg/d) or baicalin and sunitinib for 6 weeks. The tumor volume and weight of tumor-bearing mice were measured, and cardiovascular functions were evaluated by testing the Heart index and blood biochemical indicators, and by H&E, Masson and TUNEL staining. Results: Sunitinib therapy and combination therapy effectively inhibited the growth of renal tumors. Combination therapy inhibited sunitinib-induced increase of creatine kinase (CK) and lactate dehydrogenase (LDH), and ameliorated the heart parameters. Moreover, baicalin effectively protected SU-induced cardiac dysfunction by decreased the injury, apoptosis, and fibrosis.  Conclusion: Collectively, our results demonstrate that baicalin as a potential cardioprotective approach for cardiovascular complications during sunitinib regimen.  </p

Discovery of late Changhsingian (latest Permian) brachiopod Attenuatella species from South China

Attenuatella mengi sp. nov. and ?Attenuatella sp. from the Talung Formation, southern Guangxi Zhuang Autonomous Region, South China, are described herein. This discovery represents the first report of Attenuatella from the late Changhsingian (latest Permian) in South China and provides evidence that Attenuatella expanded its range from high-latitude cold-water regions to palaeoequatorial warm water areas in the Late Permian. Attenuatellaspecies appear to have been pseudoplanktonic, judging from their hair-like spinose ornamentation, which could have contributed to the global palaeogeographical distribution of Attenuatella.<br /

Liquiritigenin Protects Rats from Carbon Tetrachloride Induced Hepatic Injury through PGC-1α Pathway

The lack of effective treatment for liver cirrhosis and hepatocellular carcinomas imposes serious challenges to the healthcare system. Here, we investigated the efficacy and mechanism of liquiritigenin involved in preventing or retarding the progression of liver diseases in a rat model with chronic carbon tetrachloride (CCl4) exposure. Sprague Dawley rats were given CCl4 and lliquiritigenin alone or simultaneously for 8 weeks before liver was harvested to check histological changes by Hematoxylin and Eosin (H&E) staining, apoptosis by TUNEL assay, ROS by dihydroethidium staining, antioxidant enzyme activities and malondialdehyde using specific kits, and gene expression by quantitative real-time PCR and western blot. Chronic CCl4 exposure caused profound changes in liver histology with extensive hepatocyte death (necrosis and apoptosis), fat accumulation, and infiltration of inflammatory cells, accompanied by depressed activities of antioxidant enzymes, increased oxidative stress, elevated expression of inflammation and fibrotic genes, and downregulation of PGC-1α, ND1, and Bcl-x in rat liver. All these changes were abolished or alleviated by lliquiritigenin. The results demonstrated that liquiritigenin is effective in protecting liver from injury or treating chronic liver diseases. The modulation of PGC-1α and its downstream genes might play a critical role in relieving CCl4-induced hepatic pathogenesis by liquiritigenin

Mucoadhesive Thiolated Hyaluronic Acid/Pluronic F127 Nanogel Formation <i>via</i> Thiol–Maleimide Click Reaction for Intravesical Drug Delivery

The development of nanocarriers to prolong the residence time and enhance the permeability of chemotherapeutic drugs on bladder mucosa is important in the postsurgery treatment of superficial bladder cancers (BCs). Here, the mucoadhesive HA-SH/PF127 nanogels composed of a temperature-sensitive Pluronic F127 (PF127) core and thiolated hyaluronic acid (HA-SH) shell were prepared by the emulsification/solvent evaporation method. The nanogels were constructed through the thiol-maleimide click reaction in the HA-SH aqueous side of the oil–water interface and self-oxidized cross-linking thiols between HA-SH. The HA-SH/PF127 nanogels prepared at different thiol-to-maleimide group molar ratios, water-to-oil volume ratios, and cross-linking reaction times were characterized regarding hydrodynamic diameter (Dh) and zeta potential (ζ), and the optimal formulation was obtained. The excellent mucoadhesive properties of the HA-SH/PF127 nanogels were evaluated by using the mucin particle method. Doxorubicin (DOX) was encapsulated in the PF127 core of DOX@HA-SH/PF127 nanogels with a high loading efficiency (87.5%) and sustained release from the nanogels in artificial urine. Ex vivo studies on porcine bladder mucosa showed that the DOX@HA-SH/PF127 nanogels enhanced the penetration of the DOX into the bladder mucosa without disrupting the mucus structure or the bladder tissue. A significant dose-dependent cytotoxic effect of DOX@HA-SH/PF127 nanogels on both T24 and MB49 cells was observed. The present study demonstrates that the mucoadhesive HA-SH/PF127 nanogels are a promising intravesical drug delivery system for superficial BC therapy