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Ubiquitination, a pivotal posttranslational modification of proteins, plays a fundamental role in regulating protein stability. The dysregulation of ubiquitinating and deubiquitinating enzymes is a common feature in various cancers, underscoring the imperative to investigate ubiquitin ligases and deubiquitinases (DUBs) for insights into oncogenic processes and the development of therapeutic interventions. In this review, we discuss the contributions of the ubiquitin-proteasome system (UPS) in all hallmarks of cancer and progress in drug discovery. We delve into the multiple functions of the UPS in oncology, including its regulation of multiple cancer-associated pathways, its role in metabolic reprogramming, its engagement with tumor immune responses, its function in phenotypic plasticity and polymorphic microbiomes, and other essential cellular functions. Furthermore, we provide a comprehensive overview of novel anticancer strategies that leverage the UPS, including the development and application of proteolysis targeting chimeras (PROTACs) and molecular glues.
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Enzimas Desubicuitinizantes , Neoplasias , Complejo de la Endopetidasa Proteasomal , Ubiquitinación , Humanos , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Animales , Complejo de la Endopetidasa Proteasomal/metabolismo , Enzimas Desubicuitinizantes/metabolismo , Proteolisis , Ubiquitina/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Procesamiento Proteico-Postraduccional , Terapia Molecular Dirigida , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
The existence of potential pathogens may lead to severe water pollution, disease transmission, and the risk of infectious diseases, posing threats to the stability of aquatic ecosystems and human health. In-depth research on the dynamic of potential pathogenic communities is of significant importance, it can provide crucial support for assessing the health status of aquatic ecosystems, maintaining ecological balance, promoting sustainable economic development, and safeguarding human health. Nevertheless, the current understanding of the distribution and geographic patterns of potential pathogens in coastal ecosystems remains rather limited. Here, we investigated the diversity, assembly, and co-occurrence network of potential pathogenic communities in two anthropogenic coastal regions, i.e., the eight mouths (EPR) and nearshore region (NSE), of the Pearl River Estuary (PRE) and a total of 11 potential pathogenic types were detected. The composition and diversity of potential pathogenic communities exhibited noteworthy distinctions between the EPR and NSE, with 6 shared potential pathogenic families. Additionally, in the NSE, a significant pattern of geographic decay was observed, whereas in the EPR, the pattern of geographic decay was not significant. Based on the Stegen null model, it was noted that undominant processes (53.36%/69.24%) and heterogeneous selection (27.35%/25.19%) dominated the assembly of potential pathogenic communities in EPR and NSE. Co-occurrence network analysis showed higher number of nodes, a lower average path length and graph diameter, as well as higher level of negative co-occurrences and modularity in EPR than those in NSE, indicating more complex and stable correlations between potential pathogens in EPR. These findings lay the groundwork for the effective management of potential pathogens, offering essential information for ecosystem conservation and public health considerations in the anthropogenic coastal regions.
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The postharvest decay of chestnuts (Castanea mollissima Blume) limits their industrial utilization, and pathogenic fungi are the main cause for chestnut decay. In this study, the physiological changes and their correlation with the rotting degree of chestnuts were investigated during single or mixed infection by Fusarium proliferatum, Penicillium crustosum, and Alternaria alternata. During the infection period, the activities of cell wall degrading enzymes (CWDEs) and antioxidant enzymes firstly increased and then decreased, the contents of nutrients decreased, but the levels of physiological indexes increased. The mycelium and spores of pathogenic fungi colonized the intercellular space, and then the mycelium covered the entire tissue surface of chestnuts, leading to the disappearance of cell structure. Notably, the most prominent changes in physiological indexes and ultrastructure were observed in chestnuts infected with three pathogenic fungi. Furthermore, the rotting degree of chestnuts was positively correlated with the levels of CWDEs, antioxidant enzymes and malondialdehyde.
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PURPOSE: Kallmann syndrome is a rare disease characterized by delayed puberty, infertility and anosmia. We report the clinical and genetic characteristics of three patients with Kallmann syndrome who presented with Klinefelter syndrome and defined this neglected combined form of hypogonadism as mixed hypogonadism. METHODS: Clinical data and examinations were obtained, including laboratory examination and magnetic resonance imagination (MRI) of the olfactory structures. Congenital hypogonadotropic hypogonadism (CHH) related genes were screened by next generation sequencing (NGS). RESULTS: Three patients with Kallmann syndrome were included. They had co-existence with Klinefelter syndrome and showed hypogonadotropic hypogonadism. Patient 1 was complicated with germinoma. CONCLUSION: Mixed hypogonadism was defined as hypogonadotropic hypogonadism in Klinefelter syndrome or primary testicular disease. Clinicians should be alert to mixed hypogonadism when spermatogenesis induction failed in patients with CHH or gonadotropin levels decrease in patients with Klinefelter syndrome.
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Hipogonadismo , Infertilidad , Síndrome de Kallmann , Síndrome de Klinefelter , Masculino , Humanos , Síndrome de Kallmann/complicaciones , Síndrome de Klinefelter/complicaciones , Hipogonadismo/etiología , TestículoRESUMEN
OBJECTIVE: To compare the effects of combined gonadotropin and pulsatile gonadotropin-releasing hormone (GnRH) therapy on spermatogenesis in patients with pituitary stalk interruption syndrome (PSIS). METHODS: Male patients with PSIS (N = 119) were retrospectively studied. Patients received pulsatile GnRH therapy (N = 59) were divided into response and poor-response groups based on luteinizing hormone (LH) levels after 1-month treatment with a cutoff value of 1 or 2 IU/L. Participants with gonadotropin therapy were divided into human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) group (N = 60), and patients with pulsatile GnRH therapy were classified into GnRH group (N = 28) with treatment duration ≥6 months. RESULTS: The overall success rates of spermatogenesis for hMG/hCG and GnRH therapy were 51.67% (31/60) vs 33.90% (20/59), respectively. GnRH group required a shorter period to induce spermatogenesis (8 vs 15 months, P = .019). hMG/hCG group had higher median total testosterone than GnRH group [2.16, interquartile range(IQR) 1.06-4.89 vs 1.31, IQR 0.21-2.26 ng/mL, P = .004]. GnRH therapy had a beneficial effect on spermatogenesis compared to hMG/hCG therapy (hazard ratio 1.97, 95% confidence interval 1.08-3.57, P = .026). In patients with pulsatile GnRH therapy, compared with the poor-response group, the response group had a higher successful spermatogenesis rate (5.00% vs 48.72%, P = .002) and higher median basal total testosterone (0.00, IQR 0.00-0.03 vs 0.04, IQR 0.00-0.16 ng/mL, P = .026) with LH = 1 IU/L as the cutoff value after 1-month pulsatile GnRH therapy. CONCLUSIONS: Pulsatile GnRH therapy was superior to hMG/hCG therapy for spermatogenesis in patients with PSIS. Earlier spermatogenesis and higher concentrations of sperm could be obtained in the GnRH group if patients received therapy over 6 months.
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Hipogonadismo , Enfermedades de la Hipófisis , Humanos , Masculino , Hormona Liberadora de Gonadotropina/farmacología , Hormona Liberadora de Gonadotropina/uso terapéutico , Estudios Retrospectivos , Hormona Folículo Estimulante/farmacología , Hormona Folículo Estimulante/uso terapéutico , Hormona Luteinizante/farmacología , Hormona Luteinizante/uso terapéutico , Semen , Espermatogénesis , Gonadotropina Coriónica/farmacología , Gonadotropina Coriónica/uso terapéutico , Menotropinas/uso terapéutico , Menotropinas/farmacología , Síndrome , Testosterona/uso terapéutico , HipófisisRESUMEN
AIMS: We aimed to investigate whether peripheral T-cell subsets could be a biomarker to distinguish major depressive disorder (MDD) and bipolar disorder (BD). METHODS: Medical records of hospitalized patients in the Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2015 to September 2020 with a discharge diagnosis of MDD or BD were reviewed. Patients who underwent peripheral blood examination of T-cell subtype proportions, including CD3+, CD4+, CD8+ T-cell, and natural killer (NK) cells, were enrolled. The Chi-square test, t-test, or one-way analysis of variance were used to analyze group differences. Demographic profiles and T-cell data were used to construct a random forest classifier-based diagnostic model. RESULTS: Totally, 98 cases of BD mania, 459 cases of BD depression (BD-D), and 458 cases of MDD were included. There were significant differences in the proportions of CD3+, CD4+, CD8+ T-cell, and NK cells among the three groups. Compared with MDD, the BD-D group showed higher CD8+ but lower CD4+ T-cell and a significantly lower ratio of CD4+ and CD8+ proportions. The random forest model achieved an area under the curve of 0.77 (95% confidence interval: 0.71-0.83) to distinguish BD-D from MDD patients. CONCLUSION: These findings imply that BD and MDD patients may harbor different T-cell inflammatory patterns, which could be a potential diagnostic biomarker for mood disorders.
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Trastorno Bipolar , Trastorno Depresivo Mayor , Humanos , Trastorno Bipolar/diagnóstico , Trastorno Depresivo Mayor/diagnóstico , Estudios Retrospectivos , Subgrupos de Linfocitos T , BiomarcadoresRESUMEN
Leaf is the main photosynthetic organ in plants and the primary energy source all along the plant life. Given the beneficial role of leaf rolling in improving photosynthetic efficiency and yield in specific environmental conditions, a better understanding of the factors and molecular mechanisms underlying this process is highly suited. Previously, the SlARF4 knocking out mutant exhibited upward curly leaf showed higher resistance to water deficit which driving us to uncover the function of SlARF4 in regulating the curly leaf formation. In this study, we unraveled the unexplored role of the SlARF4-SlHB8 module of transcription factors in the development of leaf rolling. Both SlARF4 loss-of-function and SlHB8 overexpressing tomato plants exhibited upward-rolled leaves, reflecting the active role of the two genes in controlling leaf rolling. Dual-luciferase reporter assays and phenotypic analysis of hybrid progenies suggested that SlHB8 acts downstream of SlARF4 in curly leaf formation. SlARF4 and SlHB8 influence the development of leaf palisade tissues via modulating the expression of genes associated with curly leaf formation. SEM analysis revealed no significant differences in leaf epidermal cells between the two leaf-rolling mutants and the wild type, indicating that curly leaves of arf4 and SlHB8-OE do not result from the asymmetric leaf epidermal cell growth. Our data provide novel insight into the molecular mechanism of abaxial-adaxial determination involving SlARF4 and SlHB8 and reveals that leaf rolling operates via different regulation mechanisms in tomato and Arabidopsis model plant.
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Arabidopsis , Solanum lycopersicum , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Solanum lycopersicum/genética , Fenotipo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Hojas de la Planta/metabolismo , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
To comprehensively elucidate the ecology of the bacterial community and antibiotic resistance genes (ARGs) in urbanised coastal ecosystems, this study investigated the variations of bacterial community and five common types of ARGs, the impacting factors and assembly of bacterial community, as well as their co-occurrence relationships in two ecosystems of the Pearl River Estuary (PRE). The bacterial community composition and structure of the nearshore ecosystem (NSE) and the eight mouths of the PRE (EPR) markedly differed, with 38 phyla shared between these two ecosystems. The abundances of 10 ARGs and bacterial community diversity were significantly higher in the EPR than NSE. Moreover, 67.82% and 27.82% of the variation in the bacterial community was explained by spatial (44.42%/8.63%) and environmental (23.40%/19.19%) variables in the NSE and EPR, respectively. Significant distance-decay patterns were observed, and distinct stochastic processes (undominated processes or dispersal limitation) dominated bacterial community assembly in the NSE and EPR. Furthermore, co-occurrence patterns showed significant positive correlations between 48/182 ASVs belonging to 6/15 bacterial phyla and 8/11 ARGs in the NSE/EPR, with six common dominant hosts. These results clarify the drivers and mechanism shaping the bacterial community, providing further proof for potential ARG bacterial hosts in urbanised estuarine ecosystems.
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Antibacterianos , Ecosistema , Antibacterianos/farmacología , Genes Bacterianos , Ríos/microbiología , Estuarios , Bacterias/genética , Farmacorresistencia Microbiana/genética , ChinaRESUMEN
Aedes albopictus (Diptera: Culicidae) is a major vector of multiple diseases. While vaccines have been developed, preventing these Aedes-borne diseases continues to primarily depend on monitoring and controlling the vector population. Despite increasing research on the impacts of various factors on Ae. albopictus population dynamics, there is still no consensus on how meteorological or environmental factors affect vector distribution. In this study, the relationships between mosquito abundance and meteorological and environmental indicators were examined at the town level based on data collected from July to September, the peak abundance period of 2019 in Shanghai. In addition to performing Poisson regression, we employed the geographically weighted Poisson regression model to account for spatial dependency and heterogeneity. The result showed that the environmental factors (notably human population density, the Normalized Difference Vegetation Index (NDVI), socioeconomic deprivation, and road density) had more significant impacts than the meteorological variables in accounting for the spatial variation of mosquito abundance at a city scale. The dominant environmental variable differed in urban and rural places. Furthermore, our findings indicated that deprived townships are more susceptible to higher vector densities compared to non-deprived townships. Therefore, it is crucial not only to allocate more resources but also to increase attention towards controlling the vectors responsible for their transmission in these townships.
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Aedes , Animales , Humanos , China , Ciudades , Dinámica Poblacional , Análisis Espacial , Mosquitos VectoresRESUMEN
Background: Emotional blunting is prevalent in patients with mood disorders and adversely affects the overall treatment outcome. The Oxford Depression Questionnaire is a validated psychometric instrument for assessing emotional blunting. We aimed to evaluate the reliability and validity of the Chinese version of the ODQ (ODQ) in Chinese patients with mood disorders. Methods: 136 mood disorders patients and 95 healthy control participants were recruited at the First Affiliated Hospital of Zhejiang University, School of Medicine. Patients were assessed using the ODQ, Beck Depression Inventory-II (BDI-II), and Montgomery-Asberg Depression Rating Scale (MADRS). Internal consistency reliability and test-retest reliability were analyzed. Confirmatory factor analysis and correlation analysis were used to evaluate construct and convergent validity. Results: A total of 136 patients with mood disorders and 95 healthy controls participated in this study. Cronbach α values were 0.928 (ODQ-20) and 0.945 (ODQ-26). Test-retest reliability coefficients were 0.798 (ODQ-20) and 0.836 (ODQ-26) (p<0.05); intraclass correlation coefficient values were 0.777 (ODQ-20) and 0.781 (ODQ-26) (p<0.01). The score of ODQ was positively correlated with BDI-II and MADRS (r=0.326~0.719, 0.235~0.537, p<0.01). The differences in the ODQ scores between the patient and control groups were statistically significant. Conclusion: The reliability, structural validity, and criterion validity of the ODQ applied to patients with mood disorders meet the psychometric requirements, and the scale can be used to assess emotional blunting in Chinese patients with mood disorders.
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Emotion suppression is widely assumed to be unhealthy. Yet, this conclusion may be limited to independent Western cultures that value self-expression. In a pre-registered, daily diary study of European American and East Asian college students, we tested whether culture moderates the effects of daily use of emotion suppression on sleep-a critical component of healthy living among young adults. A total of 117 college students (62 European Americans and 55 East Asians) completed two diaries per day for 14 days to assess (a) their daily use of emotion suppression every night and (b) subjective sleep quality and mood upon awakening every morning. Participants also wore actigraphy watches to provide behavioral measures of sleep. The data were collected between 2018 and 2020. We used multilevel models to test cultural differences in the effects of emotion suppression on sleep and mood measures at both between-person (average) and within-person (day-to-day) levels. For European Americans, greater use of emotion suppression across 2 weeks was associated with lower average subjective sleep quality and more tense (vs. calm) feelings upon awakening. At the within-person level, on days when European Americans used emotion suppression more than usual, they had less amount of sleep that night. In contrast, these associations were completely absent among East Asians. These results provide support for the cultural fit hypothesis that how emotion suppression affects sleep health varies by cultural contexts, depending on whether this regulatory behavior is normatively congruous or incongruous with the values prioritized in each culture. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Emociones , Sueño , Adulto Joven , Humanos , Afecto , Estudiantes/psicología , BlancoRESUMEN
Perovskite nanopillars (PNPs) are propitious candidates for solar irradiation harvesting and are potential alternatives to thin films in flexible photovoltaics. To realize efficient daily energy output, photovoltaics must absorb sunlight over a broad range of incident angles and wavelengths congruent with the solar spectrum. Herein, we report highly periodic three-dimensional (3D) PNP-based flexible photovoltaics possessing a core-shell structure. The vertically aligned PNP arrays demonstrate up to 95.70% and 75.10% absorption at peak and under an incident angle of 60°. The efficient absorption and the orthogonal carrier collection facilitate an external quantum efficiency of 84.0%-89.18% for broadband wavelength. PNPs have been successfully implemented in flexible solar cells. The porous alumina membrane protects PNPs against water and oxygen intrusion and thereby imparts robustness to photovoltaic devices. Meanwhile, the excellent tolerance to mechanical stress/strain enables our unique PNP-based device to provide efficient solar-to-electricity conversion while undergoing mechanical bending.
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Objective: The aim of this study was to evaluate the diagnostic accuracy of different olfactory evaluation tools in congenital hypogonadotropic hypogonadism (CHH) patients. Methods: Seventy-one CHH patients were prospectively recruited at Peking Union Medical College Hospital between November 2020 and July 2021. The Chinese Olfactory Function Test (COFT) and Self-reported Olfactory Scale (SROS) were adapted as the subjective tools for the evaluation of olfactory function, and magnetic resonance imaging of olfactory apparatus (MRI-OA) was the objective tool. The olfactory bulb volume (OBV) and the olfactory sulcus depth (OSD) were quantified. Results: Based on the COFT, 36 patients were categorized as having normosmic CHH (nCHH), and the other 35 patients were categorized as having Kallmann syndrome (KS). Among nCHH patients, 35 patients were classified as having normal olfaction and 1 patient had abnormal olfaction by SROS. For KS patients, there were 30 patients grouped into abnormal olfaction, while 5 patients had normal olfaction by SROS. For MRI-OA, 67% (18/27) of nCHH patients showed normal olfactory apparatus, and 33% (9/27) showed bilateral or unilateral olfactory bulb aplasia or hypoplasia. Among KS patients, 96% (27/28) of patients showed bilateral olfactory bulb hypoplasia or aplasia, and 4% (1/28) of patients showed normal olfactory apparatus. All six patients with unilateral olfactory bulb aplasia and three patients with bilateral olfactory bulb aplasia showed normal olfactory function. The accuracy of the SROS in the diagnosis of nCHH and KS was 91.5%, with a sensitivity of 0.857 and a specificity of 0.972, while the accuracy of MRI-OA is 92.7%, with a sensitivity of 0.964 and a specificity of 0.889. Conclusion: SROS and MRI-OA both showed high accuracy to distinguish between KS and nCHH. The abnormal structure of the olfactory apparatus was relatively common in nCHH patients. CHH patients with unilateral olfactory bulb aplasia dysplasia usually had normal olfaction. Normal olfaction without apparent olfactory bulbs is rare but occurred in male CHH patients.
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Síndrome de Kallmann , Olfato , Pueblo Asiatico , Humanos , Hiperplasia , Síndrome de Kallmann/complicaciones , Síndrome de Kallmann/diagnóstico , Masculino , AutoinformeRESUMEN
OBJECTIVE: This study aimed to determine the clinical indicators influencing bone mineral density (BMD) of the lumbar spine and femoral neck in patients with pituitary stalk interruption syndrome (PSIS) who underwent multiple hormone replacement therapy (MHRT). METHODS: Male patients with PSIS (n = 51) who underwent MHRT for at least 1 year were enrolled in this study. Their BMD parameters were recorded and compared with age-, weight-, and height-matched control adults. In addition, we performed multiple linear regression analysis to correlate clinical parameters with BMD parameters at 2 different sites. RESULTS: Fifty-one patients with PSIS had a mean age of 30.39 ± 5.50 years. After 36 months of treatment, patients with PSIS who underwent MHRT had slightly lower BMD than those in the control group. Multiple linear regression models revealed a positive association between the Z-score values for the lumbar spine with treatment duration (r = 0.453, P < .001), insulin-like growth factor-1 (IGF-1) standard deviation score (SDS) values (r = 0.248, P = .038), and total testosterone level (r = 0.260, P = .036) and a positive association between the Z-score values for the femoral neck with treatment duration (r = 0.425, P < .001) and IGF-1 SDS values (r = 0.338, P = .009). CONCLUSION: Collectively, long-term MHRT improves bone density in patients with PSIS to the normal range. A combination of recombinant human growth hormone replacement is more beneficial to the BMD than non-recombinant human growth hormone treatment. Moreover, serum IGF-1 contributes to femoral and lumbar mineralization, whereas serum testosterone plays a role in lumbar mineralization.
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Hormona de Crecimiento Humana , Enfermedades de la Hipófisis , Adulto , Humanos , Masculino , Adulto Joven , Densidad Ósea , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hormona de Crecimiento Humana/uso terapéutico , Testosterona , Hipófisis/diagnóstico por imagenRESUMEN
Purpose: To explore the clinical indications of using the nerve-sparing technique in radical prostatectomy. Patients and methods: We retrospectively analyzed the clinical and pathological data of 101 patients who underwent radical prostatectomy (RP) at our institution. Twenty-five patients underwent open surgery, and 76 patients underwent laparoscopic surgery. The biochemical recurrence (BCR) rate was analyzed by the method of Kaplan-Meier. The distance between the ipsilateral neurovascular bundles (NVBs) and foci of prostate tumor (N-T distance) was measured in postoperative specimens. We defined the N-T distance >2 mm as the threshold to perform nerve-sparing (NS) in RP. Through logistic regression analysis, we determined the preoperative clinical indications for the nerve-sparing technique in RP. Results: The average BCR-free survival time was 53.2 months in these 101 patients with RP, with the 3- and 5-year BCR-free rates being 87.9% and 85.8%, respectively. The N-T distance was measured in 184 prostate sides from postoperative specimens of 101 patients. Univariate analysis showed that the percent of side-specific biopsy cores with cancer (≥1/3), maximum tumor length in biopsy core (≥5 mm), average percent involvement of each positive core (≥50%), PI-RADS score, and prostate MP-MRI imaging (extra-capsular extension) were associated with the N-T distance (p < 0.003). Furthermore, the percent of side-specific biopsy cores with cancer (≥1/3) (OR = 4.11, p = 0.0047) and prostate MP-MRI imaging (extra-capsular extension) (OR = 3.92, p = 0.0061) were found to be statistically significant independent predictors of the N-T distance in multivariate analysis. Conclusions: The clinical indications of nerve-sparing RP were <1/3 side-specific biopsy cores with cancer and no extra-capsular extension by prostate MP-MRI examination.
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Acute kidney injury is a frequent complication in the clinical setting and associated with significant morbidity and mortality. Preconditioning with short-term caloric restriction is highly protective against kidney injury in rodent ischemia reperfusion injury models. However, the underlying mechanisms are unknown hampering clinical translation. Here, we examined the molecular basis of caloric restriction-mediated protection to elucidate the principles of kidney stress resistance. Analysis of an RNAseq dataset after caloric restriction identified Cyp4a12a, a cytochrome exclusively expressed in male mice, to be strongly downregulated after caloric restriction. Kidney ischemia reperfusion injury robustly induced acute kidney injury in male mice and this damage could be markedly attenuated by pretreatment with caloric restriction. In females, damage was significantly less pronounced and preconditioning with caloric restriction had only little effect. Tissue concentrations of the metabolic product of Cyp4a12a, 20-hydroxyeicosatetraenoic acid (20-HETE), were found to be significantly reduced by caloric restriction. Conversely, intraperitoneal supplementation of 20-HETE in preconditioned males partly abrogated the protective potential of caloric restriction. Interestingly, this effect was accompanied by a partial reversal of caloric restriction--induced changes in protein but not RNA expression pointing towards inflammation, endoplasmic reticulum stress and lipid metabolism. Thus, our findings provide an insight into the mechanisms underlying kidney protection by caloric restriction. Hence, understanding the mediators of preconditioning is an important prerequisite for moving towards translation to the clinical setting.
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Lesión Renal Aguda , Daño por Reperfusión , Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/prevención & control , Animales , Restricción Calórica , Ácidos Hidroxieicosatetraenoicos/metabolismo , Ácidos Hidroxieicosatetraenoicos/farmacología , Riñón/metabolismo , Masculino , Ratones , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & controlRESUMEN
Background: Gonadotropins are effective in inducing spermatogenesis in patients with congenital combined pituitary hormone deficiency (CCPHD). Data on recombinant human growth hormone(rhGH) adjuvant treatment to improve gonadotropin-induced spermatogenesis are limited. Design and Setting: This retrospective study included 60 male patients with CCPHD on a relatively large case series in a single center from mainland China. Twenty-nine patients who received gonadotropin therapy alone were defined as the Gn group, while 31 patients treated with a combination of rhGH and gonadotropins were defined as GH/Gn group. Results: Spermatogenesis rate was 96.77% (30/31) and 62.07% (18/29) in the GH/Gn and Gn group, respectively (P < 0.001). The time for initial sperm appearance in the GH/Gn group was shorter than in the Gn group (14 versus 23 months, P < 0.001). A higher level of serum testosterone was achieved in the GH/Gn group than in the Gn group (4.79 versus 3.38 ng/mL, P = 0.026). After adjustment for potential confounders, rhGH supplementation was an independent beneficial factor on spermatogenesis (HR = 2.294, 95% CI: 1.143-4.604, P = 0.019). Conclusions: rhGH induces earlier spermatogenesis in patients with CCPHD, which encourages the co-treatment with rhGH and gonadotropins in CCPHD patients.
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Hormona de Crecimiento Humana , Hipopituitarismo , Espermatogénesis , Adulto , Gonadotropinas/uso terapéutico , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Hipopituitarismo/tratamiento farmacológico , Masculino , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , TestosteronaRESUMEN
The intricate processes of microbiota-gut-brain communication in modulating human cognition and emotion, especially in the context of mood disorders, have remained elusive. Here we performed faecal metagenomic, serum metabolomics and neuroimaging studies on a cohort of 109 unmedicated patients with depressed bipolar disorder (BD) patients and 40 healthy controls (HCs) to characterise the microbial-gut-brain axis in BD. Across over 12,000 measured metabolic features, we observed a large discrepancy (73.54%) in the serum metabolome between BD patients and HCs, spotting differentially abundant microbial-derived neuroactive metabolites including multiple B-vitamins, kynurenic acid, gamma-aminobutyric acid and short-chain fatty acids. These metabolites could be linked to the abundance of gut microbiota presented with corresponding biosynthetic potentials, including Akkermansia muciniphila, Citrobacter spp. (Citrobacter freundii and Citrobacter werkmanii), Phascolarctobacterium spp., Yersinia spp. (Yersinia frederiksenii and Yersinia aleksiciae), Enterobacter spp. (Enterobacter cloacae and Enterobacter kobei) and Flavobacterium spp. Based on functional neuroimaging, BD-related neuroactive microbes and metabolites were discovered as potential markers associated with BD-typical features of functional connectivity of brain networks, hinting at aberrant cognitive function, emotion regulation, and interoception. Our study combines gut microbiota and neuroactive metabolites with brain functional connectivity, thereby revealing potential signalling pathways from the microbiota to the gut and the brain, which may have a role in the pathophysiology of BD.
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Trastorno Bipolar , Microbioma Gastrointestinal , Microbiota , Humanos , Microbioma Gastrointestinal/genética , Trastorno Bipolar/metabolismo , Eje Cerebro-Intestino , Metaboloma , Encéfalo/metabolismoRESUMEN
BACKGROUND: Pituitary stalk interruption syndrome (PSIS), characterized by thinning or disappearance of the pituitary stalk, hypoplasia of the anterior pituitary, and an ectopic posterior pituitary, can lead to congenital combined pituitary hormone deficiency. There is a high prevalence of various metabolic disorders, including nonalcoholic fatty liver disease (NAFLD), in this population. OBJECTIVE: To investigate the characteristics of NAFLD in Chinese adult patients with PSIS and its association with growth hormone deficiency. DESIGN: Retrospective cross-sectional study in a tertiary referral center of China. PATIENTS: Adult patients with PSIS diagnosed, followed up between September 2019 and August 2021, were consecutively enrolled. MEASUREMENTS: Abdominal ultrasonography images were evaluated and noninvasive fibrosis scores were determined to assess the severity of NAFLD. Anthropometric, clinical, and biochemical parameters were compared between patients with and without NAFLD. Logistic regression was performed to assess the independent effects of insulin-like growth factor-1 (IGF-1) on NAFLD. RESULTS: A total of 93 patients (77 men, 16 women, mean age: 29.6 ± 7.1 years) were included. The prevalence of NAFLD and advanced fibrosis/cirrhosis was 50.5% and 4.3%, respectively. Insufficient hormone therapy and prominent metabolic disorders, including central obesity, dyslipidemia, insulin resistance, and metabolic syndrome, were more common in the NAFLD (+) group. After adjusting for multiple variables, IGF-1 <-2 standard deviation score (SDS) was found to be associated with an increased prevalence of NAFLD (odds ratio [OR]: 4.92, 95% confidence interval [CI]: 1.21-24.55, p = .035). Per 1 SDS increase in IGF-1 was associated with a 27% lower risk of NAFLD (OR: 0.73, 95% CI: 0.52-0.97, p = .042). CONCLUSION: NAFLD is a frequent comorbidity among Chinese adult patients with PSIS and is strongly associated with lower IGF-1 levels. Timely and appropriate hormone replacement, particularly growth hormone may contribute to decreasing the risk of NAFLD in these patients.