FGF13 enhances resistance to platinum drugs by regulating hCTR1 and ATP7A via a microtubule-stabilizing effect.

Platinum-based regimens are the most widely used chemotherapy regimens, but cancer cells often develop resistance, which impedes therapy outcome for patients. Previous studies have shown that fibroblast growth factor 13 (FGF13) is associated with resistance to platinum drugs in HeLa cells. However, the mechanism and universality of this effect have not been clarified. Here, we found that FGF13 was associated with poor platinum-based chemotherapy outcomes in a variety of cancers, such as lung, endometrial, and cervical cancers, through bioinformatics analysis. We then found that FGF13 simultaneously regulates the expression and distribution of hCTR1 and ATP7A in cancer cells, causes reduced platinum influx, and promotes platinum sequestration and efflux upon cisplatin exposure. We subsequently observed that FGF13-mediated platinum resistance requires the microtubule-stabilizing effect of FGF13. Only overexpression of FGF13 with the -SMIYRQQQ- tubulin-binding domain could induce the platinum resistance effect. This phenomenon was also observed in SK-MES-1 cells, KLE cells, and 5637 cells. Our research reveals the mechanism of FGF13-induced platinum drug resistance and suggests that FGF13 can be a sensibilization target and prognostic biomarker for chemotherapy.

[Effects of PM2.5 exposure on Klebsiella pneumoniae clearance in the lungs of rats].

OBJECTIVE: To investigate the effects of PM2.5 exposure on susceptibility to Klebsiella infection and bacterial clearance, and to discuss its possible mechanisms. METHODS: Eighty-six healthy male SD rats were randomly divided into 4 groups: a control group, a Klebsiella pneumoniae infection group(infection group), a PM2.5 group and a PM2.5+ Klebsiella pneumoniae infection group (combined group) .We developed a rat model in which the animals were given Klebsiella pneumoniae, PM2.5 exposure and PM2.5 exposure followed by infection with Klebsiella pneumoniae respectively. The clinical scores were evaluated. The total mortality of each group was assessed. Bacterial load in the BALF was quantified and the infection rate of each group was assessed.Lung histopathological changes were detected by HE staining. The concentrations of IL-6 and TNF-α in serum were detected by ELISA. Cells in the BALF were counted for each group by microscopy. The changes of tracheal membrane epithelial cells were observed by scanning electron microscope. RESULTS: The total mortality in the combined group (n = 14) was higher than that in the control group (n = 0), infection group(n = 4) and PM2.5 group(n = 4). The infected cases in the combined infection group (n = 13) was higher than that in the infection group (n = 6). The total number of WBC in BALF in the combined group on the first day[(11.96 ± 0.56)×10(5)/L] and seventh day [(15.68 ± 0.81)×10(5)/L] was higher than that in the control group, the infection group and the PM2.5 group. The neutrophil number in BALF in the combined group on the first day[(5.76 ± 0.44)×10(5)/L] and seventh day [(9.41 ± 0.64)×10(5)/L] was higher than that in the control group, the infection group and the PM2.5 group. The lung pathological changes were much more severe in the combined group as compared to those in the control, the infection and the PM2.5 groups. Concentrations of TNF-α in serum in the combined group on the first day [(829 ± 90) ng/L] and the seventh day [(1055 ± 91) ng/L] were higher than those in the control group and the PM2.5 group. Concentrations of IL-6 in serum in the combined group on the first day [(1.26 ± 0.16) ng/L] and seventh day [(1.95 ± 0.18) ng/L] was higher than those in the control, the infection and the PM2.5 groups. Tracheal cilia in the PM2.5 group showed signs of disorderly arrangement, adhesion and ecclasis. CONCLUSIONS: PM2.5 exposure increased the susceptibility of the rats to Klebsiella pneumoniae infection and decreased bacterial clearance.Its mechanism may be related to impairment of the bronchial mucociliary system and interaction of cytokines.

Impact of COVID-19 convalescence on pregnancy outcomes in patients undergoing IVF/ICSI during fresh ART cycles: a retrospective cohort study.

Objective: The aim was to study the impact of coronavirus disease 2019 (COVID-19) convalescence on female fertility and laboratory and clinical outcomes in fresh assisted reproductive technology (ART) cycles. Methods: In this retrospective cohort study, we analyzed data from 294 patients who had recovered from COVID-19 and who underwent fresh ART cycles between January and March 2023 (COVID-19 group). This group was compared with 631 patients who underwent similar ART cycles in the same period in 2022 but without having been infected with COVID-19 (non-COVID-19 group). The analysis focused on comparison of basic demographic characteristics and laboratory parameters of patients in each group. The primary outcome measure was the clinical pregnancy rate, which was examined to assess the impact of COVID-19 infection on the efficacy of ART treatment. Results: Basal follicle-stimulating hormone (FSH) levels were significantly lower and antral follicle count (AFC) was markedly higher in the COVID-19 group compared to the non-COVID-19 group (P<0.001 and P=0.004, respectively). The predominant ovarian stimulation protocol in the COVID-19 group was GnRH antagonists (64.85%, P<0.001), with a reduced gonadotropin (Gn) dosage and duration in comparison to the non-COVID-19 group (P<0.05). Although the number of blastocysts formed was lower in the COVID-19 group (P=0.017), this group also exhibited a higher blastocyst freezing rate and a higher rate of high-quality embryos per retrieved oocyte (P<0.001 and P=0.023, respectively). Binary logistic regression analysis indicated that COVID-19 convalescence did not significantly impact clinical pregnancy rates in fresh transfer cycles (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 0.68-1.96, P=0.5874). However, smooth curve-fitting and threshold effect analysis revealed an age-related decline in clinical pregnancy rates in both groups, more pronounced in the COVID-19 group, for women aged over 38 years, with the likelihood of clinical pregnancy decreasing by 53% with each additional year of age (odds ratio [OR] = 0.81, 95% confidence interval [CI] = 0.61-1.08, P=0.1460; odds ratio [OR] = 0.47, 95% CI = 0.21-1.05, P=0.0647). Conclusions: Our findings present no substantial evidence of adverse effects on clinical pregnancy outcomes in fresh ART cycles in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) during the period of convalescence from COVID-19. However, age emerges as a significant factor influencing these outcomes. Notably, for women above 38 years of age, the likelihood of clinical pregnancy in patients with a prior COVID-19 infection decreased by 53% with each additional year. This highlights the importance of considering maternal age, especially in the context of COVID-19, when evaluating the likelihood of successful pregnancy following ART treatments.

Down-regulation of the Smad signaling by circZBTB46 via the Smad2-PDLIM5 axis to inhibit type I collagen expression.

BACKGROUND: Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood. METHODS: Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5. RESULTS: In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development. CONCLUSIONS: CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

Physiological and pathological roles of Ang II and Ang- (1-7) in the female reproductive system.

The local Renin-Angiotensin System (RAS) has been demonstrated to exist in a wide range of tissues and organs, In the female reproductive system, it is mainly found in the ovary, uterus and placenta. The RAS system is made up of a series of active substances and enzymes, in addition to the circulating endocrine renin-angiotensin system. The active peptides Angiotensin II (Ang II) and Angiotensin (1-7) (Ang-(1-7)), in particular, appear to have distinct activities in the local RAS system, which also controls blood pressure and electrolytes. Therefore, in addition to these features, angiotensin and its receptors in the reproductive system seemingly get involved in reproductive processes, such as follicle growth and development, as well as physiological functions of the placenta and uterus. In addition, changes in local RAS components may induce reproductive diseases as well as pathological states such as cancer. In most tissues, Ang II and Ang- (1-7) seem to maintain antagonistic effects, but this conclusion is not always true in the reproductive system, where they play similar functions in some physiological and pathological roles. This review investigated how Ang II, Ang- (1-7) and their receptors were expressed, localized, and active in the female reproductive system. This review also summarized their effects on follicle development, uterine and placental physiological functions. The changes of local RAS components in a series of reproductive system diseases including infertility related diseases and cancer and their influence on the occurrence and development of diseases were elucidated. This article reviews the physiological and pathological roles of Ang II and Ang- (1-7) in female reproductive system,a very intricate system of tissue factors that operate as agonists and antagonists was found. Besides, the development of novel therapeutic strategies targeting components of this system may be a research direction in future.

Influence of auricular plaster therapy on sleeping structure in OSAS patients.

OBJECTIVE: To evaluate the therapeutic effects of auricular plaster therapy for obstructive sleep apnea syndrome (OSAS) and the influence on sleeping structure. METHODS: 45 OSAS patients were randomly divided into a treatment group of 30 cases and a control group of 15 cases for comparison of the changes in parameters of respiration and sleep at night. RESULTS: The auricular plaster therapy significantly improved the hypoventilation index, respiratory disturbance index and other respiratory parameters as well as the sleeping parameters such as the time and rate of sleep at stage I and II, and the waking time and rate. CONCLUSION: Auricular plaster therapy may show good therapeutic effects for OSAS, and with the advantages of low cost and less side effects.

Effects of dihydrotestosterone on synaptic plasticity of the hippocampus in mild cognitive impairment male SAMP8 mice.

The current study focused on how dihydrotestosterone (DHT) regulates synaptic plasticity in the hippocampus of mild cognitive impairment male senescence-accelerated mouse prone 8 (SAMP8) mice. Five-month-old SAMP8 mice were divided into the control, castrated and castrated-DHT groups, in which the mice were castrated and treated with physiological doses of DHT for a period of 2 months. To determine the regulatory mechanisms of DHT in the cognitive capacity, the effects of DHT on the morphology of the synapse and the expression of synaptic marker proteins in the hippocampus were investigated using immunohistochemistry, qPCR and western blot analysis. The results showed that the expression of cAMP-response element binding protein (CREB), postsynaptic density protein 95 (PSD95), synaptophysin (SYN) and developmentally regulated brain protein (Drebrin) was reduced in the castrated group compared to the control group. However, DHT promoted the expression of CREB, PSD95, SYN and Drebrin in the hippocampus of the castrated-DHT group. Thus, androgen depletion impaired the synaptic plasticity in the hippocampus of SAMP8 and accelerated the development of Alzheimer's disease (AD)-like neuropathology, suggesting that a similar mechanism may underlie the increased risk for AD in men with low testosterone. In addition, DHT regulated synaptic plasticity in the hippocampus of mild cognitive impairment (MCI) SAMP8 mice and delayed the progression of disease to Alzheimer's dementia. In conclusion, androgen-based hormone therapy is a potentially useful strategy for preventing the progression of MCI in aging men. Androgens enhance synaptic markers (SYN, PSD95, and Drebrin), activate CREB, modulate the fundamental biology of synaptic structure, and lead to the structural changes of plasticity in the hippocampus, all of which result in improved cognitive function.

[The change and significance of the cardiopulmonary exercise test parameters in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investigate the change of exercise cardiopulmonary function in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Thirty OSAHS patients and 18 normal healthy adults (control group) were studied by cardiopulmonary exercise test (CPET). The results including maximal oxygen uptake percent predicted (Vo(2)max% predicted), oxygen uptake to work rate (Vo(2)/WR), oxygen pulse percent predicted (Vo(2)/HRmax% predicted), anaerobic threshold to maximal oxygen uptake (AT/Vo(2)max), breathing reserve (V(E)max/MVV) and ventilatory equivalents for carbon dioxide (V(E)/V(CO2)) were compared between two groups. RESULTS: The levels of Vo(2)max% predicted, AT/Vo(2)max, Vo(2)/HRmax% predicted, Vo(2)/WR, and V(E)max/MVV in the OSAHS group [(83 +/- 5)%, (44 +/- 6)%, (79 +/- 5)%, (9.3 +/- 0.6) ml.min(-1).W(-1), (73 +/- 8)%] were lower than those in the control group [(88 +/- 5)%, (49 +/- 6)%, (83 +/- 4)%, (10.9 +/- 2.3) ml.min(-1).W(-1), (79 +/- 9)%, all P < 0.05]. The levels of V(E)/V(CO2) in the OSAHS group (29 +/- 3) was higher than the control group (26 +/- 3, P < 0.05). In the OSAHS group Vo(2)max% predicted, Vo(2)/HRmax% predicted, Vo(2)/WR AT/Vo(2)max and V(E)max/MVV correlated negatively with apnea-hypopnea index (AHI, r = -0.52, -0.62, -0.59, -0.37, -0.66, P < 0.05). Vo(2)max% predicted, Vo(2)/HRmax% predicted, Vo(2)/WR, AT/Vo(2)max and V(E)max/MVV correlated with lowest oxygen saturation (LSaO(2), r = 0.60, 0.63, 0.64, 0.40, 0.59, P < 0.05). V(E)/V(CO2) correlated with AHI (r = 0.57, P < 0.01) and correlated negatively with LSaO(2) (r = -0.62, P < 0.01). CONCLUSIONS: The cardiac output of patients with OSAHS can not meet the demand of hard exercise. At the same time, there is more significant ventilation-perfusion disturbance in OSAHS patients than normal subjects. The patients' exercise cardiopulmonary function has been compromised although there are no symptoms.

[Study on hemodynamic changes and cardiac troponin I level in pig model of acute experimental pulmonary embolism].

OBJECTIVE: To evaluate the hemodynamic effects and cardiac troponin I (cTn I), creatine kinase-MB (CK-MB), myoglobin (Mb) releasing kinetics of acute experimental pulmonary embolism of pigs. METHODS: Sixteen juvenile pigs, of either gender and weighing 30 to 40 kg were studied, 8 in the embolism group and 8 in the control group. The 8 embolism animals received 0.1 g/kg polystyrene beads (diameter range 0.65 to 0.67 mm) suspended in 0.9% saline by venous injection. Pulmonary arterial pressure (PAP), systemic arterial pressure (SAP), pulmonary capillary wedged pressure (PCWP), cardiac output (CO), blood gases and serum cTn I, CK-MB, and Mb were measured before and immediately, 30 min, 1 hour, 2 hour, and 3 hour after acute pulmonary embolism. RESULTS: PAP was increased to 2 - 3 fold of the baseline and the control level immediately, and then decreased to the baseline level in 2 to 3 hours. Serum cTn I and Mb increased significantly after embolism and remained at a higher level through the 3 hour experimental procedure. The CK-MB was not changed after acute pulmonary embolism. CONCLUSIONS: Acute pulmonary embolism caused lung gas exchange abnormality and acute pulmonary hypertension. The hemodynamic effects of acute pulmonary embolism include injury to the myocardial cells and releasing of cTn I and Mb to blood stream. cTn I can be detected in the early phase of acute pulmonary embolism, and maybe a useful marker in diagnosis and management of acute pulmonary embolism.

Lobar pneumonia caused by Ralstonia pickettii in a sixty-five-year-old Han Chinese man: a case report.

INTRODUCTION: Ralstonia pickettii is a gram-negative, oxidase-positive bacillus and is an emerging pathogen found in infections described in hospital settings. The cases reported in the literature mostly are nosocomial infections due to contaminated blood products, sterile water, saline, treatment fluids and venous catheters. Human infection unrelated to contaminated solutions is rare. We report a case of lobar pneumonia and pulmonary abscess caused by Ralstonia pickettii in an older patient. CASE PRESENTATION: A sixty-five-year old Han Chinese man presented having had cough, expectoration, chest pain and fever lasting for twenty days. His medical history was notable for hypertension over the previous ten years, and the habit of smoking for forty years. A thoracic computed tomography scan supported the diagnosis of right-sided lobar pneumonia. A lung biopsy was done and pathological analysis confirmed lobar pneumonia. Two lung biopsy specimens from separate sites grew Ralstonia pickettii. After six days, a repeat thoracic scan revealed a right-sided abscess. A thoracentesis was performed and the purulent fluid grew Ralstonia pickettii. The chest tube remained inserted to rinse the cavity with sterile sodium chloride. He received an antibiotic course of intravenous cefoperazone sodium-sulbactam sodium for eighteen days and imipenem-cilastatin for twelve days. A repeat chest X-ray revealed resolution of the pulmonary abscess and improvement of pneumonia. He remained afebrile and free of respiratory symptoms after treatments. CONCLUSION: This case demonstrates a Ralstonia pickettii infection in the absence of an obvious nosocomial source. It is possible that such cases will become common in the future. Therefore, further studies are needed to evaluate its sensitivity to common antibiotics.