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Clinical studies have found that neonatal sevoflurane exposure can increase the risk of cognitive dysfunction. However, recent studies have found that it can exhibit neuroprotective effects in some situations. In this study, we aimed to explore the effects of sevoflurane neonatal exposure in rats. A total of 144 rat pups (72 males and 72 females) were assigned to six groups and separately according to sevoflurane exposure of different times on the seventh day after birth. Blood gas analysis and western blot detection in the hippocampus were conducted after exposure. The Morris water maze test was conducted on the 32nd to 38th days after birth. The expression of PSD95 and synaptophysin in the hippocampus was detected after the Morris water maze test. We found that neonatal exposure to sevoflurane promoted apoptosis in the hippocampus, and Bax and caspase-3 were increased in a dose-dependent manner. The 2-h exposure had the greatest effects on cognitive dysfunction. However, with the extension of exposure time to 6 h, the effects on cognitive function were partly compensated. In addition, sevoflurane exposure decreased synaptogenesis in the hippocampus. However, as the exposure time was extended, the suppression of synaptogenesis was attenuated. In conclusion, neonatal sevoflurane exposure exhibited duration-dependent effects on cognitive function via Bax-caspase-3-dependent apoptosis and bidirectional effects on synaptogenesis in rats.

Abstract Osteoarthritis (OA) is defined as a degenerative joint disease that can affect all tissues of the joint, including the articular cartilage, subchondral bone, ligaments capsule, and synovial membrane. The conventional nonoperative treatments are ineffective for cartilage repair and induce only symptomatic relief. Platelet-rich plasma (PRP) is a platelet concentrate derived from autologous whole blood with a high concentration of platelets, which can exert anti-inflammatory and regenerative effects by releasing multiple growth factors and cytokines. Recent studies have shown that PRP exhibits clinical benefits in patients with OA. However, high operational and equipment requirements greatly limit the application of PRP to OA treatment. Past studies have indicated that high-concentration PRP growth factors and cytokines may be applied as a commercial replacement for PRP. We reviewed the relevant articles to summarize the feasibility and mechanisms of PRP-based growth factors in OA. The available evidence suggests that transforming growth factor-α and β, platelet-derived growth factors, epidermal growth factor, insulin-like growth factor-1, and connective tissue growth factors might benefit OA, while vascular endothelial growth factor, tumor necrosis factor-α, angiopoietin-1, and stromal cell derived factor-1α might induce negative effects on OA. The effects of fibroblast growth factor, hepatocyte growth factor, platelet factor 4, and keratinocyte growth factor on OA remain uncertain. Thus, it can be concluded that not all cytokines released by PRP are beneficial, although the therapeutic action of PRP has a valuable potential to improve.

Abstract Irinotecan is a topoisomerase I inhibitor which has been widely used to combat several solid tumors, whereas irinotecan therapy can induce liver injury. Liver injury generally leads to tissue hypoxia, and hypoxia-inducible factor-1α (HIF-1α), a pivotal transcription factor, mediates adaptive pathophysiological responses to lower oxygen condition. Previous studies have reported a relationship between HIF-1α and autophagy, and autophagy impairment is a common characteristic in a variety of diseases. Here, irinotecan (50 mg/kg) was employed on mice, and HepG2 and L-02 cells were cultured with irinotecan (10, 20 and 40 μM). In vivo study, we found that irinotecan treatment increased final liver index, serum aminotransferase level and hepatic lipid accumulation. Impaired autophagic flux and activation of HIF-1α/BNIP3 pathway were also demonstrated in the liver of irinotecan-treated mice. Moreover, irinotecan treatment significantly deteriorated hepatic oxidative stress, evidenced by increased MDA and ROS contents, as well as decreased GSH-Px, SOD and CAT contents. Interestingly, protein levels of NLRP3, cleaved-caspase 1 and IL-1β were enhanced in the liver of mice injected with irinotecan. In vitro study, irinotecan-treated HepG2 and L-02 cells also showed impaired autophagic flux, while HIF-1α inhibition efficaciously removed the accumulated autophagosomes induced by irinotecan. Additionally, irinotecan treatment aggravated lipid accumulation in HepG2 and L-02 cells, and HIF-1α inhibition reversed the effect of irinotecan. Furthermore, HIF-1α inhibition weakened irinotecan-induced NLRP3 inflammasome activation in HepG2 cells. Taken together, our results suggest that irinotecan induces liver injury by orchestrating autophagy via HIF-1α/BNIP3 pathway, and HIF-1α inhibition could alleviate irinotecan-induced lipid accumulation in HepG2 and L-02 cells, which will provide a new clue and direction for the prevention of side effects of clinical chemotherapy drugs.

Polycystic ovary syndrome is a very common disease of gynecological endocrine, accompanied by irregular menstruation, hyperandrogenism, metabolic abnormalities, reproductive disorders and other clinical symptoms, which seriously endangers women’s physical and mental health, but its etiology and pathogenesis are not completely clear. Recently, the contribution of exosomes to the diagnosis and treatment of various diseases in the biomedical field has attracted much attention, including PCOS. Exosomes are extracellular vesicles secreted by cells, containing various biologically active molecules such as cell-specific proteins, lipids, and nucleic acids. They are important signaling regulators in vivo and widely participate in various physiopathological processes. They are new targets for disease diagnosis and treatment. Considering the important role of non-coding RNAs during the development and treatment of PCOS, this article takes exosomal miRNAs as the breakthrough point for elucidating the physiological functions and therapeutic potential of exosomes during the development and treatment of PCOS through analyzing the effects of exosomal miRNAs on ovarian follicle development, hormone secretion, oxidative stress, inflammatory response and insulin resistance, thus providing new research directions and theoretical basis for PCOS pathogenesis, clinical diagnosis and prognosis improvement.

Abstract Background Sugarcane is an important crop for sugar production worldwide. The Sugars Will Eventually be Exported Transporters (SWEETs) are a group of sugar transporters recently identified in sugarcane. In Saccharum spontaneum, SsSWEET13c played a role in the sucrose transportation from the source to the sink tissues, which was found to be mainly active in the mature leaf. However, the function and regulation of SWEETs in sugarcane remain elusive despite extensive studies performed on sugar metabolism. Results In this study, we showed that SsSWEET13c is a member of SWEET gene family in S. spontaneum, constituting highest circadian rhythm-dependent expression. It is a functional gene that facilitates plant root elongation and increase fresh weight of Arabidopsis thaliana, when overexpressed. Furthermore, yeast one-hybrid assays indicate that 20 potential transcription factors (TFs) could bind to the SsSWEET13c promoter in S. spontaneum. We combined transcriptome data from developmental gradient leaf with distinct times during circadian cycles and stems/leaves at different growth stages. We have uncovered that 14 out of 20 TFs exhibited positive/negative gene expression patterns relative to SsSWEET13c. In the source tissues, SsSWEET13c was mainly positively regulated by SsbHLH34, SsTFIIIA-a, SsMYR2, SsRAP2.4 and SsbHLH035, while negatively regulated by SsABS5, SsTFIIIA-b and SsERF4. During the circadian rhythm, it was noticed that SsSWEET13c was more active in the morning than in the afternoon. It was likely due to the high level of sugar accumulation at night, which was negatively regulated by SsbZIP44, and positively regulated by SsbHLH34. Furthermore, in the sink tissues, SsSWEET13c was also active for sugar accumulation, which was positively regulated by SsbZIP44, SsTFIIIA-b, SsbHLH34 and SsTFIIIA-a, and negatively regulated by SsERF4, SsHB36, SsDEL1 and SsABS5. Our results were further supported by one-to-one yeast hybridization assay which verified that 12 potential TFs could bind to the promoter of SsSWEET13c. Conclusions A module of the regulatory network was proposed for the SsSWEET13c in the developmental gradient of leaf and circadian rhythm in S. spontaneum. These results provide a novel understanding of the function and regulation of SWEET13c during the sugar transport and biomass production in S. spontaneum.

The stiffness of the extracellular matrix of tumour cells plays a key role in tumour cell metastasis. However, it is unclear how mechanical properties regulate the cellular response to the environmental matrix. In this study, atomic force microscopy (AFM) and laser confocal imaging were used to qualitatively evaluate the relationship between substrate stiffness and migration of prostate cancer (PCa) cells. Cells cultured on stiff substrates (35 kPa) undergone several interesting phenomena compared to those on soft substrates (3 kPa). Here, the stimulation generated by the stiff substrates triggered the F-actin skeleton to bundle its filaments, increasing the polarity index of the external contour of PCa cells. Analysis of AFM force–distance curves indicated that the elasticity of the cells cultured on 35 kPa substrates increased while the viscosity decreased. Wound-healing experiments showed that PCa cells cultured on 35 kPa substrates have higher migration potential. These phenomena suggested that the mechanical properties may be correlated with the migration of PCa cells. After actin depolymerisation, the elasticity of the PCa cells decreased while the viscosity increased, and the migration ability was correspondingly decreased. In conclusion, this study clearly demonstrated the relationship between substrate stiffness and the mechanical properties of cells in prostate tumour metastasis, providing a basis for understanding the changes in the biomechanical properties at a single-cell level.

With the acceleration of life pace and the increase of work pressure, the problem of male infertility has become a social problem of general concern. Sphingolipids are important regulators of many cellular processes like cell differentiation and apoptosis, which are ubiquitously expressed in all mammalian cells. Various sphingolipid catabolic enzymes can generate multiple sphingolipids like sphingosine-1-phosphate and sphingomyelin. Present studies have already demonstrated the role of steroid hormones in the physiological processes of reproduction and development through hypothalamus-pituitary-gonad axis, while recent researches also found not only sphingolipids can modulate steroid hormone secretion, but also steroid hormones can control sphingolipid metabolites, indicating the role of sphingolipid metabolites in the homeostasis of steroid hormones. Furthermore, sphingolipid metabolites not only contribute to the regulation of gametogenesis, but also mediate damage-induced germ apoptosis, implying the role of sphingolipid metabolites in the maintenance of testicular functions. Together, sphingolipid metabolites are involved in impaired gonadal function and infertility in males, and further understanding of these bioactive sphingolipids will help us develop new therapeutics for male infertility in the future.

Cotton gauze is widely used as haemostatic material for bleeding control, but its high blood absorption capacity can to cause extra blood loss. Here, the authors develop a cotton gauze whose surface is modified with a catechol compound featuring a flexible long hydrophobic alkyl chain which demonstrates excellent haemostatic performance.

Abstract The mating compatibility in fungi is generally governed by genes located within a single or two unlinked mating type (MAT) loci. Hypsizygus marmoreus is an edible mushroom in the order Agaricales with a tetrapolar system, which contains two unlinked MAT loci-homeodomain (HD) transcription factor genes and pheromone/pheromone receptor genes (P/R). In this study, we analyzed the genetic structure and diversity of MAT loci in tetrapolar system of H. marmoreus through sequencing of 54 heterokaryon and 8 homokaryon strains. Although within the HD loci, the gene order was conserved, the gene contents were variable, and the HD loci haplotypes were further classified into four types. By analyzing the structure, phylogeny, and the HD transmissibility based on the progeny of these four HD mating-type loci types, we found that they were heritable and tightly linked at the HD loci. The P/R loci genes were found to comprise three pheromone receptors, three pheromones, and two pheromone receptor-like genes. Intra- and inter-specific phylogenetic analyses of pheromone receptors revealed that the STE3 genes were divided into three groups, and we thus theorize that they diverged before speciation. Comparative analysis of the MAT regions among 73 Basidiomycete species indicated that the diversity of HD and P/R loci in Agaricales and Boletales may contribute to mating compatibility. The number of HD genes were not correlated with the tetrapolar or bipolar systems. In H. marmoreus, the expression levels of these genes at HD and P/R loci of compatible strains were found higher than in those of homonuclear/homokaryotic strains, indicating that these mating genes acted as switches for mating processes. Further collinear analysis of HD loci in interspecific species found that HD loci contains conserved recombination hotspots showing major rearrangements in Coprinopsis cinerea and Schizophyllum commune, suggesting different mechanisms for evolution of physically linked MAT loci in these groups. It seems likely that gene rearrangements are common in Agaricales fungi around HD loci. Together, our study provides insights into the genomic basis of mating compatibility in H. marmoreus.

Objective: Partial-thickness rotator cuff tears have a high prevalence in older people. Treatment for such tears remains controversial. Platelet-rich plasma has recently attracted attention for treating partial-thickness rotator cuff tears, due to its regenerative characteristics. However, the results of application of platelet-rich plasma in non-operative treatments are unclear. The aim of this review is to evaluate the effects on shoulder function improvement and pain relief of platelet-rich plasma injection in partial-thickness rotator cuff tears, at different follow-up times (3–6 weeks, 8–12 weeks, and more than 24 weeks after treatment) compared with placebo or corticosteroids. Design: A systematic review and meta-analysis. Methods: Several databases, including PubMed, EMBASE, and Cochrane, were searched. Eleven studies met the inclusion criteria for the meta-analysis. The quality of research was evaluated using the Cochrane risk-of-bias tool. The effectiveness of platelet-rich plasma was calculated as the difference between baseline measurements and post-injection outcomes. The standardized mean difference was used to compare different outcome scales or questionnaire measurements. Statistical analysis was performed using Stata 15.0. Results: The analysis included 11 studies, with a total of 641 patients (318 treated with platelet-rich plasma and 323 controls). Compared with placebo, platelet-rich plasma exhibited significantly better effects on shoulder function improvement and pain relief at all 3 follow-up times. Compared with other conservative treatments, platelet-rich plasma exhibited significantly better effects on shoulder function and pain relief at 8–12 weeks and at more than 24 weeks after treatment. Conclusion: This review showed positive effects on shoulder function improvement and pain relief of the use of platelet-rich plasma in treating partial-thickness rotator cuff tears, especially in relatively late stages of follow-up (more than 8 weeks) after treatment. LAY ABSTRACT Partial-thickness rotator cuff tears are common, especially in older people, and can cause shoulder pain and movement limitation. Platelet-rich plasma is a platelet concentrate made from autologous blood, which may have anti-inflammatory and healing effects. This systematic review and meta-analysis collected data from existing studies to determine the specific effects of platelet-rich plasma injection on partial-thickness rotator cuff tears. The results showed that, compared with both no treatment and other conservative treatments, platelet-rich plasma reduced pain and improved shoulder function when used to treat partial-thickness rotator cuff tears. Meanwhile, the effects were most significant at 8–12 weeks and at more than 24 weeks after treatment.

Chlorogenic acid (CGA) is a powerful antioxidant polyphenol molecule found in many diets and liquid beverages, playing a preventive and therapeutic role in various diseases caused by oxidative stress and inflammation. Recent research has found that CGA can not only improve clinical symptoms in PCOS patients but also improve follicular development, hormone status, and oxidative stress in PCOS rats, indicating the therapeutic effect of CGA on PCOS. Notably, our previous series of studies has demonstrated the expression changes and regulatory mechanisms of HIF-1alpha signaling in PCOS ovaries. Considering the regulatory effect of CGA on the HIF-1alpha pathway, the present article systematically elucidates the therapeutic role and molecular mechanisms of HIF-1alpha signaling during the treatment of PCOS by CGA, including follicular development, steroid synthesis, inflammatory response, oxidative stress, and insulin resistance, in order to further understand the mechanisms of CGA effects in different types of diseases and to provide a theoretical basis for further promoting CGA-rich diets and beverages simultaneously.

Abstract Background The dehydration-responsive element-binding proteins (DREBs) are important transcription factors that interact with a DRE/CRT (C-repeat) sequence and involve in response to multiple abiotic stresses in plants. Modern sugarcane are hybrids from the cross between Saccharum spontaneum and Saccharum officinarum, and the high sugar content is considered to the attribution of S. officinaurm, while the stress tolerance is attributed to S. spontaneum. To understand the molecular and evolutionary characterization and gene functions of the DREBs in sugarcane, based on the recent availability of the whole genome information, the present study performed a genome-wide in silico analysis of DREB genes and transcriptome analysis in the polyploidy S. spontaneum. Results Twelve DREB1 genes and six DREB2 genes were identified in S. spontaneum genome and all proteins contained a conserved AP2/ERF domain. Eleven SsDREB1 allele genes were assumed to be originated from tandem duplications, and two of them may be derived after the split of S. spontaneum and the proximal diploid species sorghum, suggesting tandem duplication contributed to the expansion of DREB1-type genes in sugarcane. Phylogenetic analysis revealed that one DREB2 gene was lost during the evolution of sugarcane. Expression profiling showed different SsDREB genes with variable expression levels in the different tissues, indicating seven SsDREB genes were likely involved in the development and photosynthesis of S. spontaneum. Furthermore, SsDREB1F, SsDREB1L, SsDREB2D, and SsDREB2F were up-regulated under drought and cold condition, suggesting that these four genes may be involved in both dehydration and cold response in sugarcane. Conclusions These findings demonstrated the important role of DREBs not only in the stress response, but also in the development and photosynthesis of S. spontaneum.

Fusarium head blight (FHB) is one of the most detrimental wheat diseases. The accurate identification of FHB severity is significant to the sustainable management of FHB and the guarantee of food production and security. A total of 2752 images with five infection levels were collected to establish an FHB severity grading dataset (FHBSGD), and a novel lightweight GSEYOLOX-s was proposed to automatically recognize the severity of FHB. The simple, parameter-free attention module (SimAM) was fused into the CSPDarknet feature extraction network to obtain more representative disease features while avoiding additional parameters. Meanwhile, the ghost convolution of the model head (G-head) was designed to achieve lightweight and speed improvements. Furthermore, the efficient intersection over union (EIoU) loss was employed to accelerate the convergence speed and improve positioning precision. The results indicate that the GSEYOLOX-s model with only 8.06 MB parameters achieved a mean average precision (mAP) of 99.23% and a detection speed of 47 frames per second (FPS), which is the best performance compared with other lightweight models, such as EfficientDet, Mobilenet-YOLOV4, YOLOV7, YOLOX series. The proposed GSEYOLOX-s was deployed on mobile terminals to assist farmers in the real-time identification of the severity of FHB and facilitate the precise management of crop diseases.

Porcine somatic cell nuclear transfer (SCNT) is currently inefficient, as 1–3.95% of reconstructed embryos survive to term; inadequate or erroneous epigenetic reprogramming of the specialized donor somatic nucleus could be a primary reason. Therefore, a locus-specific analysis of DNA methylation dynamics in embryogenesis and the DNA methylation status of gametes and donor cells used for SCNT were conducted in the following developmentally important gene loci: POU5F1, NANOG, SOX2, H19, IGF2, IGF2R, XIST; and the retrotransposon LINE-1. There were significant epigenetic differences between the gametes and the somatic donor cells. Three gamete-specific differentially methylated regions (DMRs) in POU5F1, XIST, and LINE-1 were identified. A delayed demethylation process at POU5F1 and LINE-1 loci occurred after three successive cleavages, compared to the in vitro fertilized (IVF) embryos. Although cloned embryos could undergo de-methylation and re-methylation dynamics at the DMRs of imprinted genes (H19, IGF2R, and XIST), the re-methylation process was compromised, unlike in fertilized embryos. LINE-1 loci are widely dispersed across the whole genome, and LINE-1 DMR might be a potential porcine nuclear reprogramming epi-marker. Data from observations in our present and previous studies, and two published articles were pooled to produce a schematic diagram of locus-specific, DNA methylation dynamics of cloned and IVF embryos during porcine early embryogenesis. This also indicated aberrant DNA methylation reprogramming events, including inadequate DNA demethylation and insufficient re-methylation in cloned embryos. Further research should focus on mechanisms underlying demethylation during the early cleavage of embryos and de novo DNA methylation at the blastocyst stage.

Abstract Background Sucrose phosphate synthase (SPS) genes play vital roles in sucrose production across various plant species. Modern sugarcane cultivar is derived from the hybridization between the high sugar content species Saccharum officinarum and the high stress tolerance species Saccharum spontaneum, generating one of the most complex genomes among all crops. The genomics of sugarcane SPS remains under-studied despite its profound impact on sugar yield. Results In the present study, 8 and 6 gene sequences for SPS were identified from the BAC libraries of S. officinarum and S. spontaneum, respectively. Phylogenetic analysis showed that SPSD was newly evolved in the lineage of Poaceae species with recently duplicated genes emerging from the SPSA clade. Molecular evolution analysis based on Ka/Ks ratios suggested that polyploidy reduced the selection pressure of SPS genes in Saccharum species. To explore the potential gene functions, the SPS expression patterns were analyzed based on RNA-seq and proteome dataset, and the sugar content was detected using metabolomics analysis. All the SPS members presented the trend of increasing expression in the sink-source transition along the developmental gradient of leaves, suggesting that the SPSs are involved in the photosynthesis in both Saccharum species as their function in dicots. Moreover, SPSs showed the higher expression in S. spontaneum and presented expressional preference between stem (SPSA) and leaf (SPSB) tissue, speculating they might be involved in the differentia of carbohydrate metabolism in these two Saccharum species, which required further verification from experiments. Conclusions SPSA and SPSB genes presented relatively high expression and differential expression patterns between the two Saccharum species, indicating these two SPSs are important in the formation of regulatory networks and sucrose traits in the two Saccharum species. SPSB was suggested to be a major contributor to the sugar accumulation because it presented the highest expressional level and its expression positively correlated with sugar content. The recently duplicated SPSD2 presented divergent expression levels between the two Saccharum species and the relative protein content levels were highest in stem, supporting the neofunctionalization of the SPSD subfamily in Saccharum.

The mechanical properties of cells could serve as an indicator for disease progression and early cancer diagnosis. This study utilized atomic force microscopy (AFM) to measure the viscoelastic properties of ovarian cancer cells and then examined the association with the invasion of ovarian cancer at the level of living single cells. Elasticity and viscosity of the ovarian cancer cells OVCAR-3 and HO-8910 are significantly lower than those of the human ovarian surface epithelial cell (HOSEpiC) control. Further examination found a dramatic increase of migration/invasion and an obvious decease of microfilament density in OVCAR-3 and HO-8910 cells. Also, there was a significant relationship between viscoelastic and biological properties among these cells. In addition, the elasticity was significantly increased in OVCAR-3 and HO-8910 cells after the treatment with the anticancer compound echinomycin (Ech), while no obvious change was found in HOSEpiC cells after Ech treatment. Interestingly, Ech seemed to have no effect on the viscosity of the cells. Ech significantly inhibited the migration/invasion and significantly increased the microfilament density in OVCAR-3 and HO-8910 cells, which was significantly related with the elasticity of the cells. An increase of elasticity and a decrease of invasion were found in OVCAR-3 and HO-8910 cells after Ech treatment. Together, this study clearly demonstrated the association of viscoelastic properties with the invasion of ovarian cancer cells and shed a light on the biomechanical changes for early diagnosis of tumor transformation and progression at single-cell level.

Objectives: To evaluate the effect of in-hospital pulmonary rehabilitation (PR) on short-term pulmonary functional recovery in patients with COVID-19.Methods: Patients with COVID-19 (n = 123) were divided into two groups (PR group or Control group) according to recipient of pulmonary rehabilitation. Six-min walk distance (6MW), heart rate (HR), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), diffusing capacity of the lung for carbon monoxide (DLCO), and CT scanning were measured at the time of discharge, 1, 4, 12, and 24 weeks.Results: At week one, both PR group and Control group showed no significant changes in pulmonary function. At 4 and 12 weeks, 6MW, HR, FVC, FEV1, and DLCO improved significantly in both groups. However, the improvement in the PR group was greater than the Control group. Pulmonary function in the PR group returned to normal at 4 weeks [FVC (% predicted, PR vs. Control): 86.27 ± 9.14 vs. 78.87 ± 7.55; FEV1 (% predicted, PR vs. Control) 88.76 ± 6.22 vs. 78.96 ± 6.91; DLCO (% predicted, PR vs. Control): 87.27 ± 6.20 vs. 77.78 ± 5.85] compared to 12 weeks in the control group [FVC (% predicted, PR vs. Control): 90.61 ± 6.05 vs. 89.96 ± 4.05; FEV1 (% predicted, PR vs. Control) 94.06 ± 0.43 vs. 93.85 ± 5.61; DLCO (% predicted, PR vs. Control): 91.99 ± 8.73 vs. 88.57 ± 5.37]. Residual lesions on CT disappeared at week 4 in 49 patients in PR group and in 28 patients in control group (p = 0.0004).Conclusion: Pulmonary rehabilitation could accelerate the recovery of pulmonary function in patients with COVID-19.

Hypoxia-inducible factor-1α (HIF-1α) is widely distributed in human cells, and it can form different signaling pathways with various upstream and downstream proteins, mediate hypoxia signals, regulate cells to produce a series of compensatory responses to hypoxia, and play an important role in the physiological and pathological processes of the body, so it is a focus of biomedical research. In recent years, various types of HIF-1α inhibitors have been designed and synthesized and are expected to become a new class of drugs for the treatment of diseases such as tumors, leukemia, diabetes, and ischemic diseases. This article mainly reviews the structure and functional regulation of HIF-1α, the modes of action of HIF-1α inhibitors, and the application of HIF-1α inhibitors during the treatment of diseases.

FoxO1 is a member of the forkhead transcription factor family subgroup O (FoxO), which is expressed in many cell types, and participates in various pathophysiological processes, including cell proliferation, apoptosis, autophagy, metabolism, inflammatory response, cytokine expression, immune differentiation, and oxidative stress resistance. Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in the women of childbearing age, which is regulated via a variety of signaling pathways. Currently, the specific mechanism underlying the pathogenesis of PCOS is still unclear. As an important transcription factor, FoxO1 activity might be involved in the pathophysiology of PCOS. PCOS has been associated with insulin resistance and low-grade inflammatory response. Therefore, the studies regarding the role of FoxO1 in the incidence and associated complications of PCOS will help provide novel ideas for establishing the treatment strategy of PCOS.

During the luteinization after ovulation in mammalian ovary, the containing cells undergo an energy consuming function re-determination process to differentiate into luteal cells under avascular environment. Previous evidences have delineated the contribution of autophagy to the cell differentiation and the catabolic homeostasis in various types of mammalian cells, whereas few interest had been focused on the involvement of autophagy in the luteinization of granulosa cells during the formation of early corpus luteum. Herein, the present study investigated that expression and contribution of autophagy during granulosa cell luteinization and early luteal development through in vivo and in vitro experiments. The results clearly demonstrated that HIF-1α/BNIP3-mediated autophagy plays a vital role in the luteinization of granulosa cells during the early luteal formation in vivo and in vitro. In the neonatal corpus luteum, HIF-1α up-regulated BNIP3 expressions, which contributed to the autophagic initiation by disrupting beclin1 from Bcl-2/beclin1 complex and protected cells from apoptosis by curbing the skew of mitochondria balance under avascular niche. Notably, Inhibition of HIF-1α activity by echinomycin enhanced the levels of cytoplasmic cytochrome c and cell apoptosis in the nascent corpus luteum. These findings revealed that HIF-1α/BNIP3-mediated autophagy enabled the process of granulosa cell luteinization and protected the granulosa-lutein cells from further apoptosis under hypoxia niche. To our knowledge, the present study firstly clarified that HIF-1α/BNIP3-mediated autophagy contributes to the luteinization of granulosa cells during the formation of pregnant corpus luteum, which will help us further understanding the luteal biology and provide us new clues for the treatment of luteal insufficiency.

Owing to the avascular structure of the ovarian follicle, proliferation of granulosa cells (GCs) and development of follicles occur under hypoxia, which is obviously different from the cell survival requirements of most mammalian cells. We hypothesized that autophagy may exert an inhibitory effect on GC apoptosis. To decipher the underlying mechanism, we constructed a rat follicular development model using pregnant mare serum gonadotropin and a cell culture experiment in hypoxic conditions (3% O2). The present results showed that the autophagy level was obviously increased and was accompanied by the concomitant elevation of hypoxia inducible factor (HIF)-1α and BNIP3 (Bcl-2/adenovirus E1B 19kDa-interacting protein 3) in GCs during follicular development. The levels of Bax (Bcl2-associated X) and Bcl-2 (B-cell lymphoma-2) were increased, while the activation of caspase-3 exhibited no obvious changes during follicular development. However, inhibition of HIF-1α attenuated the increase in Bcl-2 and promoted the increase in Bax and cleaved caspase-3. Furthermore, we observed the downregulation of BNIP3 and the decrease in autophagy after treatment with a specific HIF-1α activity inhibitor (echinomycin), indicating that HIF-1α/BNIP3 was involved in autophagy regulation in GCs in vivo. In an in vitro study, we also found that hypoxia did not obviously promote GC apoptosis, while it significantly enhanced the activation of HIF-1α/BNIP3 and the induction of autophagy. Expectedly, this effect could be reversed by 3-methyladenine (3-MA) treatment. Taken together, these findings demonstrated that hypoxia drives the activation of HIF-1α/BNIP3 signaling, which induces an increase in autophagy, protecting GC from apoptosis during follicular development.

Objective: To investigate the effect of progressive resistance training using resistance (elastic) bands on subacromial bursitis following triamcinolone acetonide injection. Design: Randomized clinical trial. Patients: A total of 68 patients with subacromial bursitis were randomized to a triamcinolone acetonide group or a triamcinolone acetonide plus resistance band training group. Methods: Visual analogue scale, Constant scores, range of motion, proprioception, and muscle strength were evaluated at pretreatment and at 3, 12 and 24 weeks’ follow-up. Re-treatment ratio was calculated at one-year follow-up. Results: At 3 and 12 weeks, both the triamcinolone acetonide group and triamcinolone acetonide plus resistance band training group showed a significant improvement in Visual analogue scale score, Constant score, range of motion, proprioception and muscle strength. Although the scores in the triamcinolone acetonide group had not increased at 24 weeks compared with baseline, the scores in the triamcinolone acetonide plus resistance band training group showed continued improvement at 24 weeks. A lower proportion of patients in the triamcinolone acetonide plus resistance band training bands group than in the triamcinolone acetonide group had received re-treatment at one-year follow-up (12.1% vs 82.9%). Conclusion: Progressive resistance training with resistance (elastic) bands has the advantages of extending the benefits of corticosteroid injection and maintaining long-term effects on shoulder function in patients with subacromial bursitis.

In mammals, developing ovarian follicles transform from primordial follicles to primary follicles, secondary follicles, and mature follicles, accompanied by changes in follicular secretory functions. FoxO3a is a member of the forkhead transcription factor family (FoxO), which plays an important role in the cell cycle, DNA damage repair, apoptosis, oxidative stress, and energy metabolism. Recent studies have shown that FOXO3a is involved in the physiological regulation of follicular development and pathological progression of related ovarian diseases, which will provide useful concepts and strategies for retarding ovarian aging, prolonging the ovarian life span, and treating ovarian diseases. Therefore, the regulation of FOXO3a expression, as well as the physiological contribution during ovarian follicular development are detailed in this paper, presenting an important reference for the further study of ovarian biology.

Renal fibrosis is a common pathological process where certain primary or secondary kidney diseases can continue to progress to the end-stage of the kidney disease; however, the molecular mechanisms underlying renal fibrosis remain unclear. Recently, research focusing on examining the function of inflammasomes has attracted a great deal of attention, and data derived from these research projects have increased our understanding of the effects and regulation of inflammasomes during renal fibrosis. Based on this, the present review summarizes recent findings in regard to NLRP3 inflammasome functions during various kidney diseases, and these findings indicate that the NLRP3 inflammasome not only mediates the inflammatory response but is also associated with pyroptosis, mitochondrial regulation, and myofibroblast differentiation during renal fibrosis. These novel findings provide us with a more in-depth understanding of the pathogenesis of renal fibrosis and will aid in the identification of new targets that can be used for the prevention and treatment of this disease.

Background: Our previous study has detected a stem cell deficiency in the renal medulla in Dahl salt-sensitive (S) rats. This study determined whether infusion of valproic acid (VA), an agent known to stimulate the stem cell function, attenuated salt-sensitive hypertension in Dahl S rats. Methods: Uninephrectomized Dahl S rats were infused with vehicle or VA (50mg/kg/d) into the renal medulla and fed with a low (LS) or high salt diet (HS). Stem cell marker and number were analyzed by immunohistochemistry, Real-time RT-PCR and Western blot. Sodium excretion and blood pressure were measured. Results: VA significantly increased the mRNA and protein levels of FGF2, a stem cell niche factor, and CD133, a stem cell marker. The number of CD133+ cells was significantly increased in the renal medulla in VA-treated rats. Meanwhile, high salt-induced increases in the mRNA level of proinflammatory factors interleukin-1β and interleukin-6 were blocked in VA-treated rats. Functionally, sodium excretion in response to the blood pressure increase and acute sodium loading was significantly enhanced, sodium retention attenuated, high salt-induced increase of blood pressure reduced in VA-treated rats. Conclusion: Activation of stem cell function by VA inhibits the activation of proinflammatory factors and attenuates salt-sensitive hypertension in Dahl S rats.

The contribution of autophagy to catabolic balance has been well-established in various types of cells, whereas the involvement of autophagy in progesterone synthesis during rat pregnancy still remains unknown. Therefore, the present study was designed to evaluate the role of autophagy in progesterone production during the luteal development of pregnant rats. The results showed autophagy-related proteins was maintained at a low level on day 10 after pregnancy, significantly induced on day 16 and subsided to a relative low level on day 21, which was consistent with the changes of serum progesterone levels. The findings further indicated the contribution of autophagy to progesterone production was regulated by inactivation of Akt/mTOR signaling during the luteal development of pregnant rats in in vivo and in vitro experiments. Further investigations revealed autophagy may be involved in the surge of progesterone production in pregnant rats, as inhibition of autophagy by 3-MA compromised serum progesterone levels. Furthermore, 3-MA treatment also leveled down the number of lipid droplets in luteal cells, implying that autophagy may affect the production of progesterone by manipulating the formation of lipid droplets in luteal cells. In addition, the results suggested that mitophagy was mobilized during the primary stage of luteolysis and inhibition of autophagy promoted the increase of redundant mitochondrial and cytoplasmic cytochrome C in luteal cells of pregnant rats. Taken together, the present study indicated that autophagy-related proteins were induced by the inactivation of Akt/mTOR signaling and then contributed to the progesterone production possibly by affecting the formation of intracellular lipid droplets during the luteal development of pregnant rats. To our knowledge, this will provide a new insight into the important mechanism of autophagy regulating progesterone production in ovaries of pregnant mammals.