Hormone Regulation in Testicular Development and Function.

The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic-pituitary-gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives.

Multifunctional Hydrogel of Recombinant Humanized Collagen Loaded with MSCs and MnO2 Accelerates Chronic Diabetic Wound Healing.

Chronic wound repair is a clinical treatment challenge. The development of multifunctional hydrogels is of great significance in the key aspects of treating chronic wounds, including reducing oxidative stress, promoting angiogenesis, and improving the natural remodeling of extracellular matrix and immune regulation. In this study, we prepared a composite hydrogel, sodium alginate (SA)@MnO2/recombinant humanized collagen III (RHC)/mesenchymal stem cells (MSCs), composed of SA, MnO2 nanoparticles, RHC, and MSCs. The hydrogel has high mechanical properties and good biocompatibility. In vitro, SA@MnO2/RHC/MSCs hydrogel effectively enhanced the formation of intricate tubular structures and angiogenesis and showed synergistic effects on cell proliferation and migration. In vivo, the SA@MnO2/RHC/MSCs hydrogel enhanced diabetes wound healing, rapid re-epithelization, favorable collagen deposition, and abundant wound angiogenesis. These findings demonstrated that the combined effects of SA, MnO2, RHC, and MSCs synergistically accelerate healing, resulting in a reduced healing time. These observed healing effects demonstrated the potential of this multifunctional hydrogel to transform chronic wound care and improve patient outcomes.

Why is Smartphone Addiction More Common in Adolescents with Harsh Parenting? Depression and Experiential Avoidance's Multiple Mediating Roles.

Purpose: Harsh parenting is positively correlated with adolescents' smartphone addiction, according to a growing corpus of studies. The various mediating processes that could underlie this link, however, are not well understood. Based upon the experiential avoidance model, the current research aimed to identify the relation between harsh parenting and adolescents' smartphone addiction and the mediating roles of adolescents' depression and experiential avoidance. Methods: We recruited 456 adolescents (female = 52.6%; Mage = 13.19 years, SD = 0.85) at a public junior high school in China to complete the harsh discipline scale, 90-item Hopkins symptom checklist, acceptance and action questionnaire version II, and smartphone addiction scale short version. SPSS24.0 was used to conduct independent samples t-test, descriptive statistics, Pearson correlation analysis and common method bias test, PROCESS were used to conduct a significance test of the chain mediation effect on the data. Age, gender, and grade were used as con-founders that were controlled in order to make cautious predictions. Results: The results showed that (1) harsh parenting was positively correlated with adolescents' depression, experiential avoidance, and smartphone addiction; (2) both depression and experiential avoidance fully mediated the link between harsh parenting and smartphone addiction; and (3) depression and experiential avoidance also sequentially mediated the link between harsh parenting and smartphone addiction. These findings have significant implications for the prevention and intervention of adolescents' smartphone addiction. Conclusion: These findings suggested that harsh parenting may have an indirect impact on smartphone addiction in both a simple way (parallel mediation) and a complicated way (serial mediation). In addition, these studies shed light on smartphone addiction prevention and intervention.

[Effects of electroacupuncture on NLRP3/Caspase-1/GSDMD axis and neurological function in rats with cerebral ischemic reperfusion].

OBJECTIVE: To investigate the neuroprotective effect of electroacupuncture (EA) at "Quchi" (LI 11) and "Zusanli" (ST 36) in the rats with cerebral ischemic reperfusion and the potential mechanism of microglia pyroptosis. METHODS: Sixty SD rats were randomly divided into a sham-operation group, a model group and an EA group, with 20 rats in each group. The Zea Longa method was employed to establish the rat model of the middle cerebral artery occlusion and reperfusion (MACO/R) in the left brain. In the EA group, since the 2nd day of modeling, EA was given at "Quchi" (LI 11) and "Zusanli" (ST 36) of right side with disperse-dense wave, 4 Hz/20 Hz in frequency and 0.2 mA in current intensity, 30 min each time, once a day for lasting 7 consecutive days. The reduction rate of cerebral blood flow was measured with laser Doppler flowmetry during operation. The neurological function of rats was observed using Zea Longa neurobehavioral score. The cerebral infarction volume was detected by TTC staining method. The microglia positive expression in the ischemic side of the cortex was detected with the immunofluorescence method. Under transmission electron microscope, the ultrastructure of cell in the ischemic cortex was observed. The mRNA expression levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1) and gasdermin D (GSDMD) in the ischemic cortex were detected using real-time PCR. RESULTS: Compared with the sham-operation group, in the model group, the reduction rate of cerebral blood flow was increased during operation (P<0.001); Zea Longa neurobehavional score and the percentage of cerebral infarction volume were increased (P<0.001), the numbers of M1-type microglia marked by CD68+ and M2-type microglia marked by TMEM119+ were elevated in the ischemic cortex (P<0.001), the mRNA expression of NLRP3, ASC, Caspase-1 and GSDMD was increased (P<0.001, P<0.01); the cytomembrane structure was destroyed, with more cell membrane pores formed in the ischemic cortex. Compared with the model group, after intervention, Zea Longa neurobehavioral score and the percentage of cerebral infarction volume were reduced (P<0.05), the number of M1-type microglia marked by CD68+ was reduced (P<0.05) and the number of M2-type microglia marked by TMEM119+ was increased (P<0.05); and the mRNA expression of NLRP3, ASC, Caspase-1 and GSDMD was decreased (P<0.01, P<0.05) in the EA group. Even though the cytomembrane structure was incomplete, there were less membrane pores presented in the ischemic cortex in the EA group after intervention. CONCLUSION: The intervention with EA attenuates the neurological dysfunction and reduces the volume of cerebral infarction in the rats with cerebral ischemic reperfusion. The underlying mechanism is related to the inhibition of microglia pyroptosis through modulating NLRP3/Caspase-1/GSDMD axis.

[Electroacupuncture promotes the repair of neurological function in ischemic stroke rats by inhi-biting cofilin rod formation].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on modified neurological severity score (mNSS), cerebral infarction volume, expression of Lim domain kinase-1 (LIMK1) and slingshot homolog-1 (SSH1) proteins, Cofilin rod formation and neural cell apoptosis in rats with ischemic stroke (IS), so as to explore its mechanisms underlying improvement of IS. METHODS: Male SD rats were randomly divided into normal, model and EA groups, with 13 rats in each group. The IS model was established by occlusion of the middle cerebral artery (MCAO) according to Zea Longa's method. EA was applied to "Quchi" (LI11) and "Zusanli" (ST36) for 30 min, once a day for 7 consecutive days. The behavioral changes of mNSS were observed before and after modeling. The volume of cerebral infarction was measured by using a small animal magnetic resonance imaging. The protein expressions of LIMK1 and SSH1 in the cerebral ischemic tissues were detected by Western blot. The density of Cofilin rod and neural cell apoptosis in cerebral ischemic area were determined by immunofluorescence staining and TUNEL staining, separately. RESULTS: After modeling, the mNSS score, cerebral infarction volume ratio, expression level of SSH1, density of Cofilin rod and the number of apoptotic cells were significantly increased (P<0.01), while the expression level of LIMK1 protein was obviously decreased in the model group relevant to the normal group (P<0.01). After 7 days' treatment, all the increased and decreased levels of the indexes mentioned above were reversed in the EA group relevant to the model group (P<0.01, P<0.05). CONCLUSION: EA of LI11 and ST36 can improve neurological function and reduce infarction range in MCAO rats, which may be related to its action in regulating the expression of LIMK1 and SSH1, inhibiting the formation of Cofilin rod and reducing apoptosis of neural cells.

[Effect of electroacupuncture invention on activities of PGC-1α/Irisin (FNDC5)/BDNF signaling in cerebral cortex, hippocampus and muscles in focal cerebral ischemic/reperfusion injury rats].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on the expression of peroxisome proliferator-activated receptor gamma coactivators-1-alpha (PGC-1α), Irisin and brain-derived neurotrophic factor (BDNF) in the ischemic peripheral cortex, hippocampus and local skeletal muscle in rats with focal cerebral ischemic/reperfusion injury (CI/RI), so as to explore its underlying mechanism of improving of CI/RI. METHODS: Male SD rats were randomly divided into 3 groups: sham-operation, model and EA (11 rats in each group). The focal CI/RI model was established by middle cerebral artery occlusion (MCAO). EA (2 Hz /15 Hz, 2 to 4 mA) was applied to "Quchi" (LI11) and "Zusanli" (ST36) of the affected side for 20 min, once a day for 7 days. Zea-Longa's score and Balance Beam score were used to evaluate the neurological and motor functions. The infarcted volume of the brain was detected by using 2,3,5-triphenyltetrazolium chloride staining. The expression levels of PGC-1α, fibronectin type III domain-containing protein 5(FNDC5) and BDNF proteins in the ischemic peripheral cortex, hippocampus and local skeletal muscle were detected by Western blot. RESULTS: Compared with the sham-operation group, the Zea-Longa's score, Balance Beam score, percentage of cerebral infarct volume were notably increased (P<0.01), while the expression levels of PGC-1α, FNDC5 and BDNF proteins in the cerebral cortex and hippocampus (not in the local muscle) were significantly down-regulated in the model group (P<0.01, P<0.05). In comparison with the model group, the increase of Zea-Longa's score, Balance Beam score, percentage of cerebral infarct volume, and the decrease of expression levels of PGC-1α, FNDC5 and BDNF proteins in the ischemic peripheral cortex and that of BDNF in the hippocampus were reversed in the EA group (P<0.01, P<0.05). No significant changes were found in the expression levels of hippocampal PGC-1α and FNDC5 proteins in the hippocampus and those of PGC-1α, FNDC5 and BDNF proteins in the local muscle after EA intervention (P>0.05). CONCLUSION: EA can improve neurological and motor functions and reduce cerebral infarction volume in CI/RI rats, which may be related to its functions in activating PGC-1α/Irisin(FNDC5)/BDNF pathway in the cerebral cortex.

Electroacupuncture Attenuates Ischemic Brain Injury and Cellular Apoptosis via Mitochondrial Translocation of Cofilin.

OBJECTIVE: To investigate the potential mechanisms of electroacupuncture (EA) to prevent ischemic stroke. METHODS: The method of middle cerebral artery occlusion (MCAO) was employed to establish a rat model of ischemic stroke. Seventy-eight Sprague-Dawley rats were divided into the sham group, MCAO + EA control (EC) group, and MCAO + EA (EA) group according to a random number table (n=26 per group). EA was applied to the acupoints of Baihui (DU 20) and Shenting (DU 24) 5 min and 6 h, respectively after the onset of MCAO. Rats in the sham and EC groups received only light isoflurane anesthesia for 30 min after MCAO. The neuroprotective effects of EA were evaluated by rota-rod test, neurological deficit scores and infarct volumes. Additionally, Nissl staining and immunostaining were performed to examine brain damage, rod formation, cellular apoptosis, and neuronal loss induced by ischemia. The activities of caspase-3, and expression levels of cofilin and p-cofilin in mitochondria and cytoplasm after ischemic injury were determined by Western blot. RESULTS: Compared with the EC group, EA significantly improved neuromotor function and cognitive ability after ischemic stroke (P<0.05 or P<0.01). Therapeutic use of EA also resulted in a significant decrease of cofilin rod formation and microtubule-associated protein-2 (MAP2) degradation in the cortical penumbra area compared with the EC rats (P<0.01). Furthermore, Western blot analysis showed that EA stimulation significantly inhibited mitochondrial translocation of cofilin and caspase-3 cleavage (P<0.05 or P<0.01). Additionally, brain damage (infarct volume and neuropathy), cellular apoptosis and neuronal loss induced by ischemia were remarkably suppressed by EA in the cortical penumbra of rats (P<0.05 or P<0.01). CONCLUSION: EA treatment after ischemic stroke may attenuate ischemic brain injury and cellular apoptosis through the regulation of mitochondrial translocation of cofilin, a novel mechanism of EA therapy.

A systematic review and meta-analysis of the effects of early mobilization therapy in patients after cardiac surgery.

BACKGROUND: Prolonged hospitalization and immobility of critical care patients elevate the risk of long-term physical and cognitive impairments. However, the therapeutic effects of early mobilization have been difficult to interpret due to variations in study populations, interventions, and outcome measures. We conducted a meta-analysis to assess the effects of early mobilization therapy on cardiac surgery patients in the intensive care unit (ICU). METHODS: PubMed, Excerpta Medica database (EMBASE), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro), and the Cochrane Library were comprehensively searched from their inception to September 2018. Randomized controlled trials were included if patients were adults (≥18 years) admitted to any ICU for cardiac surgery due to cardiovascular disease and who were treated with experimental physiotherapy initiated in the ICU (pre, post, or peri-operative). Data were extracted by 2 reviewers independently using a pre-constructed data extraction form. Length of ICU and hospital stay was evaluated as the primary outcomes. Physical function and adverse events were assessed as the secondary outcomes. Review Manager 5.3 (RevMan 5.3) was used for statistical analysis. For all dichotomous variables, relative risks or odds ratios with 95% confidence intervals (CI) were presented. For all continuous variables, mean differences (MDs) or standard MDs with 95% CIs were calculated. RESULTS: The 5 studies with a total of 652 patients were included in the data synthesis final meta-analysis. While a slight favorable effect was detected in 3 out of the 5 studies, the overall effects were not significant, even after adjusting for heterogeneity. CONCLUSIONS: This population-specific evaluation of the efficacy of early mobilization to reduce hospitalization duration suggests that intervention may not universally justify the labor barriers and resource costs in patients undergoing non-emergency cardiac surgery. PROSPERO RESEARCH REGISTRATION IDENTIFYING NUMBER: CRD42019135338.

Cofilin Inhibition by Limk1 Reduces Rod Formation and Cell Apoptosis after Ischemic Stroke.

Cofilin, a cytoskeletal actin severing protein, is essential for the initiation phase of apoptosis. The formation of cofilin rods (containing 1:1 cofilin:actin) has been studied in cultured mammalian neurons under conditions of excessive glutamate, ATP depletion (ATP-D) or oxidative stress. These conditions simulate the pathologies occurring during ischemic stroke. In this study, we investigated the potential involvement of cofilin during ischemic-stroke induced apoptosis. Transient middle cerebral artery occlusion (tMCAO) was performed to establish an experimental model of ischemic stroke. We used 2,3,5-Triphenyltetrazolium Chloride (TTC) and immunostaining of the neuronal marker neuronal nuclei (NeuN) to evaluate the evolving phases of infarction in rats subjected tMCAO. Immunostaining and TdT-mediated dUTP Nick-End Labeling (TUNEL) apoptosis staining were collaboratively used to examine cofilin rod formation and cell apoptosis in response to ischemia at different time points (2 h, 8 h, 24 h and 7 d). Our results showed that infarct volume increased initially, between the first 2 h to 24 h and became stabilized 24 h to 7 d after tMCAO. The formation of cofilin rods significantly increased in the cortical core (from 2 h) and penumbra (from 8 h), peaking at 24 h and gradually diminishing 7 d after tMCAO. Progressive accumulation of cofilin rods subsequently induced microtubule-associated protein-2 (MAP2) degradation and ischemic cell apoptosis in the infarct cortex after stroke. To further corroborate the role of activated cofilin in ischemic stroke, inhibition of cofilin by LIM kinase (Limk1) over-expression was performed. Lmik1 reduced cofilin rod formation and MAP2 degradation, and consequently, attenuated cofilin mediated-apoptosis 24 h after tMCAO. From this evidence we conclude that cofilin plays a role in the onset of ischemic-induced apoptosis and may be efficacious in future studies as a drug target for ischemic stroke.

A systematic review and meta-analysis of the effects of early mobilization therapy in patients after cardiac surgery: A protocol for systematic review.

BACKGROUND: Prolonged hospitalization and immobility of critical care patients elevates the risk of long-term physical and cognitive impairments. However, the therapeutic effects of early mobilization have been difficult to interpret due to variations in study populations, interventions, and outcome measures. This systematic review and meta-analysis aims to assess the effects of early mobilization therapy for non-emergency cardiac surgery patients in the intensive care unit (ICU). METHODS: The following databases will be used to search for relevant keywords: PubMed, Embase, CINAHL, PEDro, and the Cochrane Library from inception to September 2018 by 2 researchers independently. Randomized controlled trials (RCTs), will be included if patients are adults (≥18 years) admitted to any ICU for cardiac surgery due to cardiovascular disease and who are treated with experimental physiotherapy initiated in the ICU (pre, post, or perioperative). The Review Manager 5.3 will be used for meta-analysis and the evidence level will be assessed by using the method for Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Continuous outcomes will be presented as the weighted mean difference (WMD) or standardized mean difference (SMD) with 95% confidence interval (CI), while dichotomous data will be expressed as relative risk (RR) with 95% CI. If the included studies have existing heterogeneity (P < 0.1), a random-effects model will be used. Otherwise, we will calculate using a fixed effects model. RESULTS: This review will evaluate the effects of early mobilization on length of ICU and hospital stay, physical function and adverse events in patients with cardiac surgery patients in the ICU. CONCLUSION: This systematic review will comprehensively provide conclusive evidence of the therapeutic effect of early mobilization on cardiac surgery patients in the ICU.PROSPERO Research registration identifying number: CRD42019135338.

Clinical study on the treatment of knee osteoarthritis of Shen-Sui insufficiency syndrome type by electroacupuncture.

OBJECTIVE: To study the clinical effificacy of electroacupuncture (EA) on treating knee osteoarthritis (KOA) of Shen ()-Sui () insuffificiency (SSI) syndrome type. METHODS: A total of 245 patients (279 knees) of KOA-SSI were randomly assigned to two groups by lottery: 141 knees in the treatment group and 138 knees in the control group. The treatment group was managed with EA at the dominant points of Neixiyan (Ex-LE4) and Waixiyan (Ex-LE5) as well as the conjugate points of Xuanzhong (GB39) and Taixi (KI3) for 30 min, once a day, with 15 days as one course; 2 courses were applied with a 5-day interval in between. The control group was treated with intra-articular injection of 2 mL hyaluronic acid into the affected joint every 7 days for 5 times in total. The clinical effects on the patients in different stages were observed, and their symptom scores of knee and contents of cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E(2alpha) (PGE(2alpha)) and matrix metalloproteinases-3 (MMP-3), in the knee joint fluid were measured before and after treatment. RESULTS: The study was completed in 235 patients (263 knees); four patients (7 knees) in the treatment group and six patients (9 knees) in the control group dropped out. Comparison of therapeutic effects (excellent and effective rates) between the two groups showed insignificant differences (P>0.05). Symptom scores of knee and contents of cytokines in the knee flfluid after treatment were lowered signifificantly in the patients of stage I-III in both groups (P<0.05 or P<0.01). However, the lowering of the total symptom score of knee in the patients of stage III in the treatment group was more signifificant (P<0.05). CONCLUSIONS: EA could effectively alleviate the clinical symptoms in KOA patients of stage III, showing an effect superior to that of hyaluronic acid. EA also shows action in suppressing the secretion of IL-1, IL-6, TNF-alpha, PGE(2alpha) and MMP-3 in the knee flfluid.