The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Angiotensin II/pharmacology* ; Fibroblasts ; Mice, Inbred C57BL ; Fibrosis ; Collagen/pharmacology* ; Collagen Type I/metabolism* ; RNA, Messenger/metabolism* ; Myocardium/pathology*

The leaves of Vernonia amygdalina Delile of the family Asteraceae(also known as "bitter leaf"), rich in biological activities, are used as both medicine and food for a long time in West tropical Africa. They have been introduced into Southeast Asia and Fujian and Guangdong provinces of China in recent years. However, little is known about the properties of the plant in traditional Chinese medicine(TCM), which limits its combination with other Chinese medicinal herbs. In this study, 473 articles on V. amygdalina leaves were selected from PubMed, Web of Science, CNKI, Wanfang Data and VIP to summarize their components, pharmacological effects and clinical research. V. amygdalina leaves presented anti-microbial, hypoglycemic, anti-hypertensive, lipid-lowering, anti-tumor, anti-inflammatory, antioxidant, and other pharmacological effects. On the basis of the theory of TCM properties, the leaves were inferred to be cold in property and bitter and sweet in flavor, acting on spleen, liver, stomach and large intestine and with the functions of clearing heat, drying dampness, purging fire, removing toxin, killing insects and preventing attack of malaria. They can be used to treat dampness-heat diarrhea, interior heat and diabetes, malaria, insect accumulation and eczema(5-10 g dry leaves by decoction per day and an appropriate amount of crushed fresh leaves applying to the affected area for external use). Due to the lack of TCM properties, V. amygdalina leaves are rarely used medicinally in China. The determination of medicinal properties of the leaves is conducive to the introduction of new exotic medicinal herbs and the development of new TCM resources, which facilitated further clinical application and research and development of Chinese medicinal herbs.
Antioxidants ; Medicine, Chinese Traditional ; Plant Extracts/pharmacology* ; Plant Leaves ; Plants, Medicinal ; Vernonia

This study aims to investigate the role of slient mating-type information regulation 2 homolog 1(SIRT1)/tuberous sclerosis complex 2(TSC2)/mammalian target of rapamycin(mTOR) signaling pathways in the Periplaneta americana extract CⅡ-3-induced senescence of human leukemia K562 cells. K562 cells were cultured in vitro and treated with 0(control), 5, 10, 20, 40, 80, and 160 μg·mL~(-1) of P. americana extract CⅡ-3. Cell counting kit-8(CCK-8) and flow cytometry were employed to examine the proliferation and cell cycle of the K562 cells. Senescence-associated β-galactosidase stain kit(SA-β-gal) was used to detect the positive rate of senescent cells. Mitochondrial membrane potential was detected by flow cytometry. The relative mRNA level of telomerase reverse transcriptase(TERT) was determined by fluorescence quantitative PCR. The mRNA and protein levels of SIRT1, TSC2, and mTOR were determined by fluorescence quantitative PCR and Western blot, respectively. The results showed that CⅡ-3 significantly inhibited the proliferation of K562 cells and the treatment with 80 μg·mL~(-1) CⅡ-3 for 72 h had the highest inhibition rate. Therefore, 80 μg·mL~(-1) CⅡ-3 treatment for 72 h was selected as the standard for subsequent experiments. Compared with the control group, CⅡ-3 increased the proportion of cells arrested in G_0/G_1 phase, decreased the proportion of cells in S phase, increased the positive rate of SA-β-Gal staining, elevated the mitochondrial membrane potential and down-regulated the mRNA expression of TERT. Furthermore, the mRNA expression of SIRT1 and TSC2 was down-regulated, while the mRNA expression of mTOR was up-regulated. The protein expression of SIRT1 and p-TSC2 was down-regulated, while the protein expression of p-mTOR was up-regulated. The results indicated that P. americana extract CⅡ-3 induced the senescence of K562 cells via the SIRT1/mTOR signaling pathway.
Humans ; Animals ; Periplaneta ; Sirtuin 1/genetics* ; K562 Cells ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics* ; RNA, Messenger ; Mammals

Objective To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.Methods Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software. Results We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, p53 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4, JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes. Conclusion The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.
Humans ; Prognosis ; Apoptosis ; Regulated Cell Death ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Tumor Microenvironment

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on lung pathological phenotype and epithelial-mesenchymal transition of alveolar epithelial cells in lung fibrosis model rats caused by paraquat (PQ). Methods Lung fibrosis model was constructed by a single intraperitoneal injection of PQ (30 mg·kg

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

OBJECTIVE: To explore the clinical application of lockedge suspension combined with three steel wires vertical fixation in comminuted fracture of inferior pole of patella. METHODS: From August 2016 to May 2019, 23 patients with comminuted fracture of the lower pole of the patella, including 14 males and 9 females, were treated with lockedge suspension combined with three steel wires vertical fixation. The age ranged from 34 to 68 (55.0±1.2) years. One year after operation, the pain and function were evaluated by pain visual analogue scale(VAS) and knee flexion and extension range of motion, and the clinical efficacy was evaluated by Lysholm knee score standard. RESULTS: All 23 patients were followed up for 12 to 14, with a mean of(13.0±0.5) months. One patient had skin irritation by the tail of the steel wire, and the rest had no postoperative complications such as incision infection, internal fixation loosening and fracture displacement. The fractures of 23 patients were healed, and the healing time was 10 to 14 weeks with a mean of(12.0±1.1) weeks. The VAS score decreased from 7.96±0.93 before operation to 0.83±0.65 one year after operation. The range of knee flexion and extension activities increased from(20.30±8.69) ° before operation to 1 year after operation(127.39±6.55) °. Lysholm knee score increased from 18.48±4.00 before operation to 96.09±4.91 one year after operation(P<0.05). CONCLUSION The treatment of comminuted fracture of the lower pole of patella by lockedge suspension combined with three steel wires vertical fixation has reliable fixation and high fracture healing rate. It can meet the requirements of rapid rehabilitation and functional exercise, and the early clinical effect is satisfactory.
Adult ; Aged ; Bone Wires ; Female ; Fracture Fixation, Internal ; Fractures, Bone/surgery* ; Fractures, Comminuted/surgery* ; Humans ; Male ; Middle Aged ; Patella/surgery* ; Steel ; Treatment Outcome

Nucleocytoplasmic transport is the basic cellular activity of eukaryotic cells, which plays a role in cell physiological and pathological processes. A large amount of evidences indicate that impaired nucleocytoplasmic trafficking has emerged as a mechanism contributing to the pathology of neurodegenerative diseases. The regulation of nucleocytoplasmic transport is crucial to elucidate the pathogenesis and intervention in the neurodegenerative diseases. This article summarizes the evidences in disturbed nucleocytoplasmic transport of neurodegenerative diseases in the past two decades, further explores the directions and provides a theoretical basis for the pathogenesis and drug targets in neurodegenerative diseases.

Sleep has been widely concerned by the medical field all over the world. Sleep deprivation can cause damage to organs of the human body， which is related to the occurrence of a variety of diseases. Besides， the pathological change in different organs of the human body is also a key factor that causes or aggravates insomnia. When treating insomnia and its complications， traditional Chinese medicine （TCM） focuses on the homology of the brain and heart， and insomnia is mainly treated from the five internal organs， especially the heart and liver. Sleep duration and structure change with age. The prevalence of insomnia is higher in older individuals susceptible to complications than in the younger population. In TCM， insomnia of blood deficiency and Yin deficiency is common among the elderly. Suanzaoren Tang is a classic prescription for nourishing blood and calming the mind and it is critical in the treatment of "sleeplessness due to consumptive disease and dysphoria"， with the effects of nourishing liver blood to calm the mind and clearing internal heat to relieve dysphoria. It has good efficacy on the insomnia of the elderly caused by deficiency of Qi and blood and abnormal operation of nutrient Qi and defense Qi. Furthermore， it also shows a certain therapeutic effect on insomnia combined with cardiovascular and cerebrovascular diseases. The present study revealed the damage to the brain， heart， and liver caused by sleep deprivation and the effect of Suanzaoren Tang on the brain， heart， and liver， and clarified the facts that Suanzaoren Tang inhibited the damage to organs caused by sleep deprivation and regulated energy metabolism， thereby exploring the sedative and hypnotic mechanism of Suanzaoren Tang to provide new ideas for Suanzaoren Tang in the treatment of sleep disorders and other diseases.