Physiological Reports最新文献

Anabolic-androgenic steroids (AASs) impairment of reproduction has been reported. We investigated dose- and time-dependent effects of Nandrolone decanoate (ND) on reproductive system in comparison with Testosterone enanthate (TE). Male Wistar rats were administrated with 1, 3, and 9 mg/kg/weeks ND or 1 and 3 mg/kg/weeks TE for 8 weeks, and testicular phenotype and reproductive hormones were assessed at 4 and 8 weeks post-treatments. AASs × treatment period interaction was significant for gonadosomatic index (GSI), testosterone (T), 17β-estradiol (E₂), and luteinizing hormone (LH). At 4 weeks post-treatment, GSI was decreased in rats treated with 3 mg/kg/weeks ND and T was decreased in all ND-treated groups, while no significant changes in LH levels were observed. At 8 weeks post-treatment, GSI was decreased in rats treated with 1 and 3 mg/kg/weeks ND and with 3 mg/kg/weeks TE, T was decreased in all groups, and E₂ and LH were increased and decreased, respectively, in rats treated with 9 mg/kg/weeks ND and with 3 mg/kg/weeks TE. The testes showed histopathological defects in both ND- and TE-treated rats suggesting a delay in seminiferous cycle. This study shows AASs-induced hypogonadism at low-dose that coincided with inhibition of T biosynthesis and disruption of T feedback on pituitary.

Type III interferons (λ1, λ2, and λ3) are potent antiviral cytokines in the lung. However, their roles in nonviral lung injuries are less well understood. This study investigates the activation of type III interferon signaling in three distinct models of lung injuries caused by diverse stimuli: the bacterial pathogen Pseudomonas aeruginosa, bacterial endotoxin LPS, and the chemotherapeutic agent bleomycin. Our data show that, despite inducing a potent inflammatory response, Pseudomonas and LPS did not increase IFNλ secretion. In contrast, bleomycin instillation increased secretion of IFNλ in the airways at both early and late time points. Consistent with limited secretion, type III interferon signaling had a minimal role in the host response to both Pseudomonas and LPS, as measured by pathogen burden, inflammatory response, and lung injury. Conversely, a deficiency in type III interferon signaling led to increased inflammatory signaling and elevated acute lung injury in the bleomycin model on day 3. This elevated early injury resulted in impaired recovery in IFNLR1 knockout mice, as evidenced by their recovery from bleomycin-induced weight loss. Taken together, these data suggest a context-specific activation of type III interferon signaling, where it plays an anti-inflammatory role in the lung.

Epidemiological studies have established a link between air pollution and an elevated risk of type 2 diabetes mellitus (T2DM). This study aims to measure the impact of T2DM related to fine particulate matter (PM2.5) pollution by examining death rates and disability-adjusted life years (DALYs) from 1990 to 2019 in the United States of America. Using data from the Global Burden of Disease (GBD) database, we examined death and DALY rates per 100,000 populations in T2DM patients, specifically focusing on ambient particulate matter pollution (APMP) and household air pollution (HAP). We assessed average annual percentage change (AAPC) across various age and gender groups, states, and socio-demographic index (SDI) categories. Our findings reveal a significant decline in death rates and DALYs in the United States of America over the last 30 years, with more pronounced decreases among females and older adults. Despite national progress, state-level variations indicate complex interactions between environmental regulations, healthcare access, and socio-economic factors. Some states, such as Oregon, Idaho, and Alaska, exhibited increased AAPC. Our study emphasizes the need for targeted policies and interventions to reduce PM_2.5 exposure and further address regional disparities, ensuring continued improvement in public health outcomes.

The essential role of the inwardly rectifying potassium channel K_ir5.1 (KCNJ16) in controlling electrolyte homeostasis and blood pressure has been demonstrated in human and animal studies. Previous studies have identified several bi-allelic mutations of KCNJ16 in humans, causing severe hypokalemia, renal salt wasting, and disturbed acid-base homeostasis. Here, we identified a novel homozygous variant of KCNJ16, I26T, in an Amish patient affected with polydipsia, developmental delay, and chronic metabolic acidosis with low serum bicarbonate concentration. Subsequently, we generated the rat model with I26T mutation using Dahl salt-sensitive rat (I26T rat) to characterize this variant. The male mutant rats displayed similar blood pressure and electrolyte homeostasis under baseline and with a high salt (4% NaCl) challenge. Blood pH, HCO₃ ^- and renal damage also remained similar between WT and I26T rats after high salt challenge. Additionally, single-channel patch clamp analysis revealed similar channel activity in CHO cells overexpressed with WT and I26T mutant K_ir4.1/5.1 channels. In summary, this study reported a novel variant in KCNJ16, namely I26T, which is likely a benign variant and not associated with pathologic phenotype in either human or Dahl salt-sensitive rats, indicating that the type/location of variant should be considered when diagnosing and treating patients with KCNJ16 mutations.

The pelvic floor responds to changes in trunk pressure, elevating during low-pressure exhale and descending during high-pressure exhale. Voicing occurs during exhalation, spanning low-to-high trunk-pressure, yet it is unknown how voicing affects the pelvic floor. The aim of this study was to quantify pelvic floor response to voicing and identify if there are differences for women with stress urinary incontinence. We hypothesized that shouting would cause pelvic floor descent, with greater magnitude for incontinent women. Sixty women (38 incontinent, 22 continent) performed four voicing tasks (counting to "4" in speaking/shouting/low-pitch/high-pitch voice) while transperineal ultrasound measured changes in pelvic floor morphology. ANOVA compared variance of responses to voicing and t-tests compared groups. Bladder neck height shortened, levator plate length increased and levator plate angle decreased more during shouting compared to speaking; consistent with pelvic floor straining. There were no differences for high versus low pitch-voicing and small group differences based on continence status. Voicing causes pelvic floor muscles to strain, with greater strain during shouting. Changing vocal pitch does not affect pelvic floor morphology and incontinent women had slight differences from continent women. Voicing may be a safe way to lengthen the pelvic floor without provoking incontinence.

Sirtuin 3 has been shown to regulate endothelial function and coronary flow reserve in mice. Knockout of SIRT3 reduced endothelial nitric oxide synthase expression in the mouse hearts. In this study, we investigate whether endothelial SIRT3 regulates vascular function and myogenic responses in distal intramural branches of the left anterior descending coronary artery (CA) and middle cerebral artery (MCA) of mice. Both male and female endothelial SIRT3 knockout (SIRT3^ECKO) mice and control SIRT3^LoxP mice were used and CA and MCA were dissected and mounted in a myograph system. The myogenic response was evaluated by measuring changes in inner diameter in response to 20 mmHg stepwise increases in intraluminal pressure in PSS (active diameter) and Ca2⁺-free PSS (passive diameter). Acetylcholine (Ach)-induced endothelial-dependent relaxation (EDR) and sodium nitroprusside (SNP)-induced endothelial-independent relaxation (EIR) were examined. Our results showed that the myogenic responses were significantly impaired in both the CA and MCA of SIRT3^ECKO mice. Furthermore, female mice had worsened myogenic response in MCA. In CA, EDR was abolished in both male and female SIRT3^ECKO mice. Intriguingly, EIR was only reduced in the female mice. In MCA, EDR was reduced in male SIRT3^ECKO mice, whereas EIR was decreased in both male and female mice. Female SIRT3^ECKO mice had profound dysfunction in CA, whereas male mice exhibited more dysfunction in MCA. These data revealed a sex and organ-specific role of endothelial SIRT3 in vascular function and myogenic responses. Our study suggests that endothelial SIRT3 is necessary for maintaining vascular function and blood flow autoregulation.

Sepsis is associated with brain injury and acute brain inflammation, which can potentially transition into chronic inflammation, triggering a cascade of inflammatory responses that may lead to neurological disorders. Minocycline, recognized for its potent anti-inflammatory properties, was investigated in this study for its protective effects against sepsis-induced brain injury. Adult male C57 mice pretreated with minocycline (12.5, 25, and 50 mg/kg) 3 days before sepsis induction. An intraperitoneal injection of 5 mg/kg LPS was used to induce sepsis. Spontaneous locomotor activity (SLA) and weight changes were assessed over several days post-sepsis to monitor the recovery of the mice. The expression of inflammatory mediators and oxidative stress markers was assessed 24 h post sepsis. Septic mice exhibited significant weight loss and impaired SLA. Initially, minocycline did not attenuate the severity of weight loss (1 day) or SLA (4 h post-sepsis), but it significantly accelerated the recovery of the mice in later days. Minocycline dose-dependently mitigated sepsis-induced brain inflammation and oxidative stress. Our findings demonstrate that pretreatment with minocycline has the potential to prevent brain tissue damage and accelerate recovery from sepsis in mice, suggesting that minocycline may serve as a promising therapeutic intervention to protect against sepsis-induced neurological complications.

Depression and anxiety are common mental health disorders affecting thoughts, behaviors, and emotions. This study aimed to investigate the effect of the angiotensin II type I receptor blocker (AT1RB), valsartan, on menopause-induced depression and anxiety-like behaviors, and to elucidate possible mechanisms of action by measuring levels of nod-like receptor protein 3 (NLRP3), interleukin-1beta (IL-1β), brain-derived neurotrophic factor (BDNF), and oxidative stress in brain tissue. Thirty-two Wistar albino female rats were randomly divided into four groups (n = 8 per group): Control, AT1RB, OVX, and AT1RB + OVX. Following the bilateral ovariectomy (OVX) protocol, physiological saline was used as valsartan solvent, in a maximum volume of 0.4 mL, and valsartan was administered via intragastric gavage at a dose of 40 mg/kg/day. Depression and anxiety-like behaviors were assessed using the forced swimming test and open field test. Levels of oxidative stress markers, NLRP3, IL-1β, BDNF, and CREB were analyzed in the hippocampus and prefrontal cortex tissues. Behavioral tests indicated that depression and anxiety-like behaviors significantly increased in OVX rats (p < 0.01), while AT1RB treatment significantly reduced these behaviors (p < 0.05). In the hippocampus of OVX rats, oxidative stress (p < 0.01), NLRP3 (p < 0.05), and IL-1β (p < 0.01) levels were elevated, whereas BDNF levels were significantly decreased (p < 0.01). AT1RB treatment significantly improved oxidative stress parameters (p < 0.05) and BDNF levels (p < 0.01) but did not significantly affect the increased levels of NLRP3 and IL-1β in OVX rats. In conclusion, AT1RB has a therapeutic effect on menopause-induced depression and anxiety-like behaviors, likely by reducing oxidative stress and increasing BDNF production in the hippocampus.

Intravenous volume loading is a common treatment when hypovolemia is a potential cause of oliguria. We studied whether the effectiveness of Ringer's solution and 20% albumin in inducing diuresis differs depending on the mean arterial pressure (MAP). For this purpose, volume kinetic analysis was performed based on urine output and hemoglobin-derived plasma dilution obtained during and after 136 infusions of Ringer and 85 infusions of 20% albumin. Covariance analysis quantified the diuretic response at different arterial pressures. The results show that the diuretic response to a known plasma volume expansion was greater for Ringer's solution above a MAP of 70 mmHg, while 20% albumin was significantly more effective at lower pressures (p < 0.03). Simulations of the urinary output in response to infusion of a predefined fluid volume yielded superior efficacy for 20% albumin when the MAP was low, while Ringer's was similarly effective when the MAP averaged 100 mmHg. In conclusion, urine output in response to plasma volume expansion with 20% albumin was similar to, or even stronger, than that of Ringer's solution when the MAP was below 70 mmHg.