Gastrodin alleviates the deterioration of depressive-like behavior and glucolipid metabolism promoted by chronic stress in type 2 diabetic mice.

The growing burden of psychological stress among diabetes patients has contributed to a rising incidence of depression within this population. It is of significant importance to conduct research on the impact of stress on diabetes patients and to explore potential pharmacological interventions to counteract the stress-induced exacerbation of their condition. Gastrodin is a low molecular weight bioactive compound extracted from the rhizome of Gastrodiae elata Blume, and it may be a preventive strategy for diabetes and a novel treatment for depression symptoms. However, its relevant pharmacological mechanisms for protecting against the impacts of psychological stress in diabetic patients are unclear. In this study, we performed 5 weeks CUMS intervention and simultaneously administered gastrodin (140 mg/kg, once daily) on T2DM mice, to investigate the potential protective effects of gastrodin. The protective effect of gastrodin was evaluated by behavioral tests, biochemical analysis, histopathological examination, RT-qPCR and gut microbiota analysis. We found that the depressive-like behavior and glucolipid metabolism could be deteriorated by chronic stress in type 2 diabetic mice, while gastrodin showed a protective effect against these exacerbations by regulating HPA hormones, activating FXR and Cyp7a1, reducing inflammatory and oxidative stress responses, and regulating ileal gut microbiota abundance. Gastrodin might be a potential therapeutic agent for mitigating the deterioration of diabetes conditions due to chronic stress.

Rapid azoospermia classification by stimulated Raman scattering and second harmonic generation microscopy.

Disease diagnosis and classification pose significant challenges due to the limited capabilities of traditional methods to obtain molecular information with spatial distribution. Optical imaging techniques, utilizing (auto)fluorescence and nonlinear optical signals, introduce new dimensions for biomarkers exploration that can improve diagnosis and classification. Nevertheless, these signals often cover only a limited number of species, impeding a comprehensive assessment of the tissue microenvironment, which is crucial for effective disease diagnosis and therapy. To address this challenge, we developed a multimodal platform, termed stimulated Raman scattering and second harmonic generation microscopy (SRASH), capable of simultaneously providing both chemical bonds and structural information of tissues. Applying SRASH imaging to azoospermia patient samples, we successfully identified lipids, protein, and collagen contrasts, unveiling molecular and structural signatures for non-obstructive azoospermia. This achievement is facilitated by LiteBlendNet-Dx (LBNet-Dx), our diagnostic algorithm, which achieved an outstanding 100% sample-level accuracy in classifying azoospermia, surpassing conventional imaging modalities. As a label-free technique, SRASH imaging eliminates the requirement for sample pre-treatment, demonstrating great potential for clinical translation and enabling molecular imaging-based diagnosis and therapy.

Profile of the bile acid FXR-FGF15 pathway in the glucolipid metabolism disorder of diabetic mice suffering from chronic stress.

Background: Imbalances in bile acid (BA) synthesis and metabolism are involved in the onset of diabetes and depression in humans and rodents. However, the role of BAs and the farnesoid X receptor (FXR)/fibroblast growth factor (FGF) 15 signaling pathway in the development of diabetes and depression is still largely unknown. Therefore, we investigated the potential molecular mechanisms of BAs that may be associated with glucolipid metabolism disorders in diabetic mice subjected to chronic stress. Methods: The type 2 diabetes mellitus (T2DM) mouse model was induced by feeding mice a high-fat diet and administering an intraperitoneal injection of streptozotocin (STZ). The chronic unpredictable mild stress (CUMS) procedure was performed by introducing a series of mild stressors. Forty mice were randomly divided into the regular chow feeding group and the high-fat diet feeding group. After two weeks of feeding, the mice were randomly divided into four groups: the Control group, CUMS group, T2DM group, and T2DM+CUMS group. The T2DM group and T2DM+CUMS group received an intraperitoneal injection of STZ to induce the T2DM model. The CUMS and T2DM+CUMS groups were exposed to CUMS to induce depressive-like phenotypes. Blood and tissue samples were obtained for pertinent analysis and detection. Results: Compared with the T2DM mice, T2DM+CUMS mice had higher blood glucose and lipid levels, insulin resistance, inflammation of the liver and pancreas, impaired liver function, and increased total bile acids. These changes were accompanied by attenuated FXR signaling. Chronic stress was found to attenuate FXR expression and its downstream target, FGF15, in the ileum when compared with the T2DM group. Conclusion: FXR may play a role in the diabetic disorder of glucolipid metabolism when aggravated by chronic stress. FXR and its downstream target, FGF15, may be therapeutic targets for treating comorbid T2DM and depression.

Corrigendum: Could peripheral 5-HT level be used as a biomarker for depression diagnosis and treatment? A narrative minireview.

[This corrects the article DOI: 10.3389/fphar.2023.1149511.].

Corrigendum: Lactobacillus reuteri strain 8008 attenuated the aggravation of depressive-like behavior induced by CUMS in high-fat diet-fed mice through regulating the gut microbiota.

[This corrects the article DOI: 10.3389/fphar.2023.1149185.].

Identification of ferroptotic genes and phenotypes in idiopathic nonobstructive azoospermia.

Effective treatments for nonobstructive azoospermia (NOA), which affects 1% of all men globally, are limited by undefined pathogenic mechanisms, especially in idiopathic NOA (iNOA). Here, we tried to identify the functional ferroptosis-related genes and phenotypes involved in iNOA. Differentially expressed ferroptotic genes were identified from iNOA mRNA microarray datasets by bioinformatic analyses, and these ferroptotic genes were subsequently filtered by various algorithms. Then, receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic ability of the abovementioned genes for iNOA. Generally, 11 differentially expressed ferroptotic genes were downregulated, and five genes were upregulated in iNOA samples. Four genes, including DUSP1, GPX4, HSD17B11, and SLC2A8, were technically selected and determined to be potential biomarkers for iNOA. Subsequently, similar expression levels were validated at both the RNA and protein levels in the iNOA specimens. Finally, morphologic and biochemical assays were applied to define the ferroptotic phenotypes in testes. The ferroptotic features, like shrunken mitochondria with electron-dense membranes and a reduction in cristae were observed across various cell types within iNOA patients, accompanied by the overload of ferrous ions and increased lipid peroxidation production. Our findings demonstrated that these ferroptosis genes could be involved in the underlying pathogenesis mechanisms of iNOA by regulating ferroptosis and serve as potential diagnostic biomarkers. Also, the ferroptotic phenotypes were identified in iNOA patients.

Fingerprint Stimulated Raman Scattering Imaging Unveils Ergosteryl Ester as a Metabolic Signature of Azole-Resistant Candida albicans.

Candida albicans (C. albicans), a major fungal pathogen, causes life-threatening infections in immunocompromised individuals. Fluconazole (FLC) is recommended as first-line therapy for treatment of invasive fungal infections. However, the widespread use of FLC has resulted in increased antifungal resistance among different strains of Candida, especially C. albicans, which is a leading source of hospital-acquired infections. Here, by hyperspectral stimulated Raman scattering imaging of single fungal cells in the fingerprint window and pixel-wise spectral unmixing, we report aberrant ergosteryl ester accumulation in azole-resistant C. albicans compared to azole-susceptible species. This accumulation was a consequence of de novo lipogenesis. Lipid profiling by mass spectroscopy identified ergosterol oleate to be the major species stored in azole-resistant C. albicans. Blocking ergosterol esterification by oleate and suppressing sterol synthesis by FLC synergistically suppressed the viability of C. albicans in vitro and limited the growth of biofilm on mouse skin in vivo. Our findings highlight a metabolic marker and a new therapeutic strategy for targeting azole-resistant C. albicans by interrupting the esterified ergosterol biosynthetic pathway.

Semen parameters' mediation effect on the association between advanced paternal age and IVF clinical outcomes: A 10-year retrospective cohort study.

OBJECTIVE: To explore the mediation between advanced paternal age and the outcomes of in vitro fertilization (IVF) in a female-adjusted cohort. METHODS: The study retrospectively included couples undergoing IVF cycles between 2011 and 2020, and whose female partner was free of medical conditions that would significantly worsen clinical outcomes. Data on patient medical conditions, clinical data, and follow-up information were collected. Causal mediation effect analysis adopting both linear/logistic regression and mixed-effects models was carried out to evaluate the effect of paternal age on the outcomes. RESULTS: 21,959 IVF cycles were included in the study. Semen volume, sperm motility and sperm morphology were significantly associated (P value <0.05) with paternal age. A lower fertilization rate was associated with increased paternal age after adjustment for maternal age (adjusted OR = 0.800; 95 % CI, 0.678, 0.943; P value = 0.008). Mediation analysis revealed that A-level sperm rate and progressive rate respectively mediated 37.0 % and 41.0 % of the association between paternal age and fertilization rate. CONCLUSION: Sperm motility rate, especially A-level sperm rate and rapid progressive rate, mediated the association between advanced paternal age and lower fertilization rate in the cycles.

Lactobacillus reuteri strain 8008 attenuated the aggravation of depressive-like behavior induced by CUMS in high-fat diet-fed mice through regulating the gut microbiota.

Objective: Gut microbiota play a key role in the pathogenesis of obesity and depression. Probiotics are a preventive strategy for obesity and a novel treatment for depression symptoms. However, the ameliorative or therapeutic effect of potential probiotic candidate Lactobacillus reuteri (L. reuteri) on obesity and depression comorbidity still remains unclear. We investigated the effects of chronic unpredictable mild stress (CUMS) in high-fat diet-fed mice and the effects of Lactobacillus reuteri strain 8008 on various disease indicators of obesity and depression comorbidity disease. Methods: Forty male C57BL/6 mice were randomized into 2 groups: the normal control (NC) group (n = 10) and the high-fat diet (HFD) group (n = 30), being fed with normal diet (ND) or high-fat diet (HFD) for 8 weeks, respectively. Then the obese mice fed with HFD were randomly allocated into 3 sub-groups: the HFD group (n = 10); the HFD + CUMS group (n = 10); the HFD + CUMS + L.r group (n = 10). The latter 2 subgroups underwent CUMS for 4 weeks to build the obesity and depression comorbidity mice model. During the duration of treatment, mice were gavaged with 0.5 mL PBS solution or L. reuteri (2 × 109 CFU/mL) once a day, respectively. The body weight, food intake, organ weight, behavioral indicators, histology, blood lipids, levels of inflammatory cytokines and tight junction proteins and abundance of colonic contents bacteria were measured. Results: The obesity and depression comorbidity mice model was successfully established after HFD feeding and chronic stress. The comorbid mice demonstrated inflammatory responses increase in liver and adipose tissues, worsened damage to the intestinal barrier as well as gut microbiota disorder. Gavaged with L. reuteri attenuated depressive-like behavior, improved blood lipids and insulin resistance, reduced inflammation in liver and adipose tissues, improved intestinal tight junctions as well as the microbiome dysbiosis in obesity and depression comorbidity mice. Conclusion: Lactobacillus reuteri strain 8008 could alleviate depressive-like behaviors and related indicators of obesity disorders by regulating the gut microbiota in obesity and depression comorbid mice.

Kinetically and thermodynamically controlled one-pot growth of gold nanoshells with NIR-II absorption for multimodal imaging-guided photothermal therapy.

Since the successful clinical trial of AuroShell for photothermal therapy, there is currently intense interest in developing gold-based core-shell structures with near-infrared (NIR) absorption ranging from NIR-I (650-900 nm) to NIR-II (900-1700 nm). Here, we propose a seed-mediated successive growth approach to produce gold nanoshells on the surface of the nanoscale metal-organic framework (NMOF) of UiO-66-NH2 (UiO = the University of Oslo) in one pot. The key to this strategy is to modulate the proportion of the formaldehyde (reductant) and its regulator / oxidative product of formic acid to harness the particle nucleation and growth rate within the same system. The gold nanoshells propagate through a well-oriented and controllable diffusion growth pattern (points → facets → octahedron), which has not been identified. Most strikingly, the gold nanoshells prepared hereby exhibit an exceedingly broad and strong absorption in NIR-II with a peak beyond 1300 nm and outstanding photothermal conversion efficiency of 74.0%. Owing to such superior performance, these gold nanoshells show promising outcomes in photoacoustic (PA), computed tomography (CT), and photothermal imaging-guided photothermal therapy (PTT) for breast cancer, as demonstrated both in vitro and in vivo.

Machine learning-based clustering to identify the combined effect of the DNA fragmentation index and conventional semen parameters on in vitro fertilization outcomes.

BACKGROUND: Previous studies have demonstrated an association between male sperm quality and assisted reproduction outcomes, focusing on the effects of individual parameters and reaching controversial conclusions. The WHO 6th edition manual highlights a new semen assay, the sperm DNA fragmentation index, for use after routine semen examination. However, the combined effect of the sperm DNA fragmentation index (DFI) and routine semen parameters remains largely unknown. METHODS: We assessed the combined effect of the sperm DFI and conventional semen parameters on single fresh conventional IVF outcomes for infertile couples from January 1, 2017, to December 31, 2020. IVF outcomes were obtained from the cohort database follow-up records of the Clinical Reproductive Medicine Management System of the Third Affiliated Hospital of Guangzhou Medical University. An unsupervised K-means clustering method was applied to classify participants into several coexposure pattern groups. A multivariate logistic regression model was used for statistical analysis. RESULTS: A total of 549 live births among 1258 couples occurred during the follow-up period. A linear exposure-response relationship was observed among the sperm DFI, sperm motility, and IVF outcomes. In multivariable adjustment, increased sperm DFI values and decreased sperm motility and semen concentration levels were associated with reduced odds of favourable IVF outcomes. Four coexposure patterns were generated based on the sperm DFI and the studied semen parameters, as follows: Cluster 1 (low sperm DFI values and high sperm motility and semen concentration levels), Cluster 2 (low sperm DFI values and moderate sperm motility and semen concentration levels), Cluster 3 (low sperm DFI values and low sperm motility and semen concentration levels) and Cluster 4 (high sperm DFI values and low sperm motility and semen concentration levels). Compared with those in Cluster 1, participants in Cluster 3 and Cluster 4 had lower odds of a live birth outcome, with odds ratios (95% confidence intervals [CIs]) of 0.733 (0.537, 0.998) and 0.620 (0.394, 0.967), respectively. CONCLUSIONS: When combined with low sperm DFI values, there was no significant difference between high or moderate sperm concentration and motility levels, and both were associated with favourable IVF outcomes. Low sperm parameter levels, even when DFI values remain low, may still lead to poor IVF outcomes. Participants with high sperm DFI values and low sperm motility and semen concentration levels had the worst outcomes. Our findings offer a novel perspective for exploring the joint effects of sperm DFI and routine semen parameter values.

Could peripheral 5-HT level be used as a biomarker for depression diagnosis and treatment? A narrative minireview.

The serotonin hypothesis of depression is still influential, but the relationship between peripheral 5-HT levels and depression is still unknown. This review aimed to verify whether peripheral 5-HT levels could be used as a biomarker for depression diagnosis and treatment. PubMed and EMBASE were searched using terms appropriate to the area of research. Articles from 1957 to 2022 in the following terms were identified: depression, 5-HT, serotonin and peripheral (serum, plasma, blood platelets). 33 studies were included: seven clinical trials about periphery 5-HT levels in depressive patients compared to normal subjects, 15 clinical trials about changes of peripheral 5-HT levels in patients with depression after drug treatment and 11 animal experiments about peripheral 5-HT levels in animal models of depression. Peripheral 5-HT levels presented three different outcomes before and after antidepressant treatments: increased, decreased and no significant change. In conclusion, changes in peripheral 5-HT levels did not show consistent results among these studies. Peripheral 5-HT level could not be used as a biomarker both for depression diagnosis and for antidepressant efficacy evaluation.