Physiological Processes Research Articles

The muscle-intervertebral disc interaction mediated by L-BAIBA modulates extracellular matrix homeostasis and PANoptosis in nucleus pulposus cells.

Upon engaging in physical activity, skeletal muscle synthesizes myokines, which not only facilitate crosstalk with various organs, including the brain, adipose tissue, bone, liver, gut, pancreas, and skin but also promote intramuscular signaling. Crosstalk is vital for maintaining various physiological processes. However, the specific interactions between skeletal muscle and intervertebral discs remain largely unexplored. β-Aminoisobutyric acid (BAIBA), an exercise-induced myokine and a metabolite of branched-chain amino acids in skeletal muscle, has emerged as a key player in this context. Our study demonstrated that exercise significantly elevates BAIBA levels in skeletal muscle, plasma, and nucleus pulposus (NP) tissues. Moreover, exercise enhances extracellular matrix (ECM) synthesis in NP tissues and upregulates L-BAIBA synthase in skeletal muscle. Both in vivo and in vitro evidence revealed that L-BAIBA impedes PANoptosis and ECM degradation in NP cells by activating the AMPK/NF-κB signaling pathway. These findings suggest that exercise, coupled with the resulting increase in L-BAIBA, may serve as an effective intervention to decelerate the progression of intervertebral disc degeneration (IDD). Consequently, L-BAIBA, which originates from skeletal muscle, is a promising new therapeutic approach for IDD.

The role of choline in the physiology of reproductivity

Choline is an essential nutrient, but intake among pregnant women is insufficient – only 7% of them consume adequate amounts of choline. The discrepancy between choline requirements and actual intake raises questions about the need for choline supplementation and its potential benefits for pregnant women. The diet of the expectant mother, rich in choline, in the preconception period ensures folliculogenesis and better quality of oocytes, changes the foetal epigenome, counteracting genomic defects during intrauterine development and reducing the susceptibility to metabolic changes in adulthood. Choline is a source of methyl groups and its consumption reduces the risk of NTDs by 7 times, so a promising trend in nutritional support of pregnancy and prevention of NTDs is the intake of folates and choline in combination with other micronutrients. Choline promotes the growth, proliferation and functioning of placental cells, transport of macronutrients, and has an anti-inflammatory effect. The risk of low foetal weight is reduced by 69% when choline is added to the mother’s regular diet. A significant connection has been shown between high levels of choline in the mother and a 2-fold reduction in the risk of preeclampsia, premature birth and a significant effect on the neurodevelopment and mental health of the child – improving neurocognitive functions and reducing the risk of autism and attention deficit hyperactivity disorder. A choline supplement at a dose of 130 mg/day as part of the vitamin-mineral complex Femibion 1 is sufficient to meet the needs for this nutrient during the preconception period and in the first trimester of pregnancy. The need for choline supplementation in the pregravid period and the first trimester of pregnancy is because on folliculogenesis and oocyte protection, epigenetic programming, the effectiveness of preventing congenital malformations of the foetus, participation in metabolic and physiological processes in the placenta, reducing the risk of placenta-associated complications, influence on the development of nervous tissue and brain of the foetus and newborn.

Long-wavelength red-emitting ClO− fluorescent probe for visualizing inflammation and drug-induced renal injury

Hypochlorous acid (ClO−), a member of the reactive oxygen species (ROS) family, plays an important role in regulating physiological processes and maintaining homeostasis in the body. However, abnormal ClO− levels in the human body have been associated with a variety of pathological conditions, encompassing inflammation and kidney diseases. In this work, we have developed a novel fluorescent probe, RDNClO, specifically tailored for the sensitive detection of ClO−. RDNClO was synthesized through modifying N - (7 - (2 - carboxyphenyl) -3- (dimethylamino) - 5,6 - dihydro - 10H - benzo[c]xanthen - 10 - ylidene) - N - ethylethanaminium (RDNOH) with 1-naphthaloyl chloride moiety. Spectroscopic analyses reveal that RDNClO exhibits outstanding performance characteristics, including high selectivity, a rapid response time of <25 s, and an ultra-low detection limit of 3.7 nM. Additionally, RDNClO has demonstrated exceptional capabilities in detecting ClO− in real water samples and rapidly identifying ClO− in environmental samples, utilizing agarose as a carrier. It effectively monitors both endogenous ClO− levels in HeLa cells and exogenous ClO− levels in HEK293T cells. Furthermore, RDNClO has excelled in tracking fluctuations in ClO− levels, including in Escherichia coli, the mouse model of arthritis induced by k-carrageenan, and a mouse model of cisplatin-induced renal injury. The development of RDNClO not only establishes a robust theoretical foundation for investigating the pathogenic mechanisms of renal injury but also presents a promising tool for advancing research in this critical area.

Experimental Insights into the Formation, Reactivity, and Crosstalk of Thionitrite (SNO−) and Perthionitrite (SSNO−)

AbstractHydrogen sulfide (H2S) and nitric oxide (NO) are important gaseous biological signaling molecules that are involved in complex cellular pathways. A number of physiological processes require both H2S and NO, which has led to the proposal that different H2S/NO⋅ crosstalk species, including thionitrite (SNO−) and perthionitrite (SSNO−), are responsible for this observed codependence. Despite the importance of these S/N hybrid species, the reported properties and characterization, as well as the fundamental pathways of formation and subsequent reactivity, remain poorly understood. Herein we report new experimental insights into the fundamental reaction chemistry of pathways to form SNO− and SSNO−, including mechanisms for proton‐mediated interconversion. In addition, we demonstrate new modes of reactivity with other sulfur‐containing potential crosstalk species, including carbonyl sulfide (COS).

SLC35G1 is a highly chloride-sensitive transporter responsible for the basolateral membrane transport in intestinal citrate absorption.

The intestinal absorption of essential nutrients, especially those not readily biosynthesized, is a critical physiological process for maintaining homeostasis. Numerous studies have indicated that intestinal absorption is mediated by various membrane transporters. Citrate, a crucial bioactive compound produced as an intermediate in the Krebs cycle, is absorbed in the small intestine through carrier-mediated systems because of its high hydrophilicity. While the luminal absorption of citrate is mediated by Na+-dicarboxylate cotransporter 1 (NaDC1/SLC13A2), the mechanism governing the release of the transported citrate into the bloodstream remains unknown. Here, we explored the transporters responsible for intestinal citrate absorption at the basolateral membrane, focusing on highly expressed orphan transporters in the small intestine as candidates. Consequently, SLC35G1, originally identified as a partner of stromal interaction molecule 1, a cell surface transmembrane glycoprotein, was found to play a role in the intestinal absorption of citrate at the basolateral membrane. Furthermore, our results revealed that SLC35G1-mediated citrate transport was diminished by chloride ions at physiologically relevant extracellular concentrations. This suggests that SLC35G1, to our best knowledge, is the first transporter identified to be extremely sensitive to chloride ions among those functioning on the basolateral membrane of intestinal epithelial cells. This study provides valuable insights into the intestinal absorption of citrate and significantly contributes to elucidating the poorly understood molecular basis of the intestinal absorption system.

Zinc and its binding proteins: essential roles and therapeutic potential.

Zinc is an essential micronutrient that participates in a multitude of cellular and biochemical processes. It is indispensable for normal growth and the maintenance of physiological functions. As one of the most significant trace elements in the body, zinc fulfills three primary biological roles: catalytic, structural, and regulatory. It serves as a cofactor in over 300 enzymes, and more than 3000 proteins require zinc, underscoring its crucial role in numerous physiological processes such as cell division and growth, immune function, tissue maintenance, as well as synthesis protein and collagen synthesis. Zinc deficiency has been linked to increased oxidative stress and inflammation, which may contribute to the pathogenesis of a multitude of diseases, like neurological disorders and cancer. In addition, zinc is a key constituent of zinc-binding proteins, which play a pivotal role in maintaining cellular zinc homeostasis. This review aims to update and expand upon the understanding of zinc biology, highlighting the fundamental roles of zinc in biological processes and the health implications of zinc deficiency. This work also explores the diverse functions of zinc in immune regulation, cellular growth, and neurological health, emphasizing the need for further research to fully elucidate the therapeutic potential of zinc supplementation in disease prevention and management.

Leaf growth in third dimension: a perspective of leaf thickness from genetic regulation to ecophysiology.

Leaf thickness, the leaf growth in the third dimension as quantified by the distance between the adaxial and abaxial surface, is an indispensable aspect of leaf development. The fitness of a plant is strongly influenced by leaf thickness via modulation of major physiological processes, including photosynthesis and water use efficiency. The cellular basis of leaf thickness by alterations in either cell size or the number of cell layers is envisaged using Arabidopsis leaf thickness mutants, such as angustifolia (an) and rotundifolia (rot). Environmental factors coordinate with endogenous signaling mechanisms to exhibit leaf thickness plasticity. Plants growing in different ecological and environmental regimes show different leaf thickness attributes. However, genetic and molecular understandings of leaf thickness regulation remain largely limited. In this review, we highlight how cellular growth is transposed to fine-tune the leaf thickness via the integration of potential cues and molecular players. We further discuss the physiological significance of leaf thickness plasticity to the environmental cues that might serve as ecological adaptation enabling the plants to withstand future climatic conditions. Taken together, we seek to bridge the genetics and molecular biology of leaf thickness to its physiological significance so that leaf thickness can be systemically targeted in crop improvement programs.

Uptake, Translocation, Toxicity, and Impact of Nanoparticles on Plant Physiological Processes

The application of nanotechnology in agriculture has increased rapidly. However, the fate and effects of various nanoparticles on the soil, plants, and humans are not fully understood. Reports indicate that nanoparticles exhibit positive and negative impacts on biota due to their size, surface property, concentration within the system, and species or cell type under test. In plants, nanoparticles are translocated either by apoplast or symplast pathway or both. Also, it is not clear whether the nanoparticles entering the plant system remain as nanoparticles or are biotransformed into ionic forms or other organic compounds. Controversial results on the toxicity effects of nanomaterials on the plant system are available. In general, the nanomaterial toxicity was exerted by producing reactive oxygen species, leading to damage or denaturation of various biomolecules. The intensity of cyto- and geno-toxicity depends on the physical and chemical properties of nanoparticles. Based on the literature survey, it is observed that the effects of nanoparticles on the growth, photosynthesis, and primary and secondary metabolism of plants are both positive and negative; the response of these processes to the nanoparticle was associated with the type of nanoparticle, the concentration within the tissue, crop species, and stage of growth. Future studies should focus on addressing the key knowledge gaps in understanding the responses of plants to nanoparticles at all levels through global transcriptome, proteome, and metabolome assays and evaluating nanoparticles under field conditions at realistic exposure concentrations to determine the level of entry of nanoparticles into the food chain and assess the impact of nanoparticles on the ecosystem.

Role of the basic leucine zipper transcription factor BATF2 in modulating immune responses and inflammation in health and disease.

Basic leucine zipper transcription factor ATF-like 2 (BATF2) is a transcription factor that is known to exhibit tumor-suppressive activity in cancer cells. Within recent years, however, BATF2 has also emerged as an important transcriptional regulator of the immune system. Through its immunomodulatory function, BATF2 has been implicated in a variety of (patho)physiological processes, including host defense against infection, anti-tumor immunity, and maintenance of tissue inflammatory homeostasis. Below, we discuss recent literature that has provided insight into the role of BATF2 as a transcriptional regulator of immune responses in health and disease, including the cell types that express BATF2, the different diseases in which the immunomodulatory effects of BATF2 have been shown to play a role, and the molecular mechanisms through which BATF2 is thought to exert those effects. In doing so, we highlight that the immunological effects of BATF2 are highly context-dependent, and we point out overlap between the mechanisms of action of BATF2 in infectious disease and non-infectious disease. We also discuss areas of interest for future research, the clinical relevance of better understanding BATF2 function, and potential strategies for therapeutic modulation of BATF2.

An all-atom model of the human cardiac sodium channel in a lipid bilayer

Voltage-gated sodium channels (NaV) are complex macromolecular proteins that are responsible for the initial upstroke of an action potential in excitable cells. Appropriate function is necessary for many physiological processes such as heartbeat, voluntary muscle contraction, nerve conduction, and neurological function. Dysfunction can have life-threatening consequences. During the past decade, there have been significant advancements with ion channel structural characterization by CryoEM, yet descriptions of cytosolic components are often lacking. Many investigations have biophysically characterized reconstituted cytosolic components and their interactions. However, extrapolating the structural alterations and allosteric communication within an intact ion channel can be challenging. To address this, we have developed an all-atom model of the human cardiac sodium channel (NaV1.5) in a lipid bilayer with explicit salt and water. Our simulations contain descriptions of cytosolic components that are poorly predicted by AlphaFold and lacking in many CryoEM structures. Leveraging the latest advancements of the Amber force fields (ff19sb and Lipid21) and water model (OPC), our simulations improved protein backbone torsion angles and generated structural information across time (four independent one-microsecond simulations). Our analysis provided descriptions of lipid and solvent contacts and insight into the C-Terminal Domain - inactivation gate and inactivation gate - latch receptor interactions.

A review of vitamin D deficiency and vitamin D receptor polymorphisms in endocrine related disorders.

The endocrine system is a complex network of glands that produce and release hormones that regulate various physiological processes. In the past few decades, the human skin has been identified as an important peripheral endocrine organ that is the main site for the synthesis of vitamin D through exposure to sunlight. Mutations in downstream vitamin D-related gene pathways are associated with disease development. The vitamin D receptor (VDR) gene, which regulates the pleiotropic effects of vitamin D, has been extensively studied in adult populations. Several studies have reported the prevalence of vitamin D deficiency in children and adolescents. With changes in socioeconomic status and lifestyle, vitamin D-deficient individuals are prone to developing the disease at a young age. However, geographical and racial differences affect the association between VDR gene polymorphisms and vitamin D endocrine disorders, explaining the non-consensus effects of polymorphisms and their association with disease development across populations. In this review, we discuss the connection between the vitamin D endocrine system and polymorphisms in the gene encoding VDR in children and adolescents, focusing on its effects on growth, puberty, insulin resistance, and the immune system.

Unveiling tomorrow: Carbonic anhydrase activators and inhibitors pioneering new frontiers in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder and a principal basis of dementia in the elderly population globally. Recently, human carbonic anhydrases (hCAs, EC 4.2.1.1) were demonstrated as possible new targets for treating AD. hCAs are vital for maintaining pH balance and performing other physiological processes as they catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton. Current research indicates that hCA plays a role in brain functions critical for transmitting neural signals. Activation of carbonic anhydrase (CA) has emerged as a promising avenue in addressing memory loss and cognitive issues. Conversely, the exploration of CA inhibition represents a novel frontier in this field. By enhancing glial fitness and cerebrovascular health and blocking amyloid-β (Aβ)-induced mitochondrial dysfunction pathways, cytochrome C (CytC) release, caspase 9 activation, and H2O2 generation in neurons, CA inhibitors improve cognition and lessen the pathology caused by Aβ. Recent research has pushed hCAs into the spotlight as critical players in AD pathogenesis and precise therapeutic targets. The captivating dilemma of choosing between hCA inhibitors and activators looms large, as inhibitors reduce Aβ aggregation and improve cerebral blood flow, while activators enhance cerebrovascular functions and restore pH balance. The current review sheds light on the clinical evidence for hCAs and the roles of inhibitors and activators in AD. Additionally, this review offers a fascinating outlook on the data that may aid medicinal chemists in designing and developing new leads that are more effective and selective for upcoming in vitro and in vivo studies, allowing for the discovery and introduction of novel drug candidates for the treatment of AD to the market and into the clinical pipeline.

Augmentation of Endogenous 2-Arachidonoylglycerol Mitigates Autistic Behaviors of BTBR Mice.

The lipid-based endocannabinoid (eCB) system regulates a host of developmental, physiological, and pathological processes in the mammalian brain, and recent studies have suggested that dysfunction of eCB system may contribute to the neuropathology of autism spectrum disorder (ASD). However, specific contributions to ASD-related developmental, cognitive, and behavioral phenotypes remain largely unexplored. The current study was designed to investigate if enhancing eCB signaling by blocking 2-arachidonoylglycerol (2-AG) hydrolase can mitigate ASD-like behaviors in a mouse model, and if such effects are associated with suppression of inflammatory signaling, oxidative stress, or neuronal apoptosis. Intraperitoneal injection of the 2-AG hydrolase monoacylglycerol lipase (MAGL) JZL184 (4, 16, or 40mg/kg) elevated 2-AG and reversed eCB system metabolic enzymes and receptors expression deficits in BTBR T + ltpr3tf/J (BTBR) mouse model of ASD. Moreover, the hyperactivity, excessive stereotypy, impaired social behavior, and cognitive deficits characteristic of this animal model were significantly improved by JZL184. Concomitantly, JZL184 administration reversed the abnormal pro- and anti-inflammatory cytokine concentrations measured in the hippocampus of BTBR mice. In addition, JZL184 reversed the observed overexpression of pro-apoptotic Bax and underexpression of anti-apoptotic Bcl-2 in BTBR mice and enhanced neuronal numbers in hippocampal CA1 and CA3 regions. We also found that the behavioral test battery influenced eCB concentrations independently of JZL184 treatment. Collectively, these findings suggest that augmenting eCB signaling can mitigate ASD-related phenotypes by suppressing neuroinflammation and neuronal apoptosis.

GDF15 is required for maintaining subcutaneous adipose tissue lipid metabolic signature

Recent research has identified growth differentiation factor 15 (GDF15) as a crucial factor in various physiological and pathological processes, particularly in energy balance regulation. While the role of GDF15 in modulating energy metabolism through hindbrain GDNF family receptor alpha-like (GFRAL) signaling has been extensively studied, emerging evidence suggests direct peripheral metabolic actions of GDF15. Using knockout mouse models, we investigated GDF15 and GFRAL’s roles in adipose tissue metabolism. Our findings indicate that C57BL/6/129/SvJ Gdf15-KO mice exhibit impaired expression of de novo lipogenesis enzymes in subcutaneous adipose tissue (sWAT). In contrast, C57BL/6J Gfral-KO mice showed no impairments compared to wild-type (WT) littermates. RNA-Seq analysis of sWAT in Gdf15-KO mice revealed a broad downregulation of genes involved in lipid metabolism. Importantly, our study uncovered sex-specific effects, with females being more affected by GDF15 loss than males. Additionally, we observed a fasting-induced upregulation of GDF15 gene expression in sWAT of both mice and humans, reinforcing this factor’s role in adipose tissue lipid metabolism. In conclusion, our research highlights an essential role for GDF15 in sWAT lipid metabolic homeostasis. These insights enhance our understanding of GDF15’s functions in adipose tissue physiology and underscore its potential as a therapeutic target for metabolic disorders.

Genome-wide methylation and transcriptome differential analysis of skeletal muscle in broilers with valgus-varus deformity

ABSTRACT 1. Valgus-varus deformity (VVD) is a disease that severely affects leg function in broilers and for which there is no effective control method current available. Although DNA methylation has an important impact on most physiological and pathological processes, its involvement in skeletal muscle growth and development in VVD broilers is unknown. In this study, genome-wide DNA methylation was analysed in VVD-affected and normal broilers using whole genome resulphite sequencing. 2. The results showed that in the cytosine-phosphoric acid-guanine (CG) sequence environment there was a methylation rate of about 55% and 4,265 differentially methylated regions (DMRs) were found in the CG. Of these, 550 were located in the promoter, 547 in the exon region, and 1,718 in the intron region. 3. All differentially methylated genes (DMGs) were analysed for enrichment of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The GO was enriched in pathways related to protein degradation such as proteasome complex, endopeptidase complex and extracellular region. The KEGG pathways were enriched in signalling pathways related to protein degradation and catabolism such as proteasome, nitrogen metabolism, adherens junction and alanine. 4. Protein interactions analysis revealed that FOS, MYL9, and FRAS1 had a high degree of interactions, in which the DNA methylation level of the MYL9 promoter region was negatively correlated with mRNA expression level. Further studies showed that 5-azacytidine (5-AzaC) inhibited DNMT1 and DNMT3A gene expression and promoted MYL9 expression. 5. This study systematically investigated overall DNA methylation patterns in the leg muscle of VVD and normal broilers. It screened common differential genes in conjunction with transcriptomic data to further identify genes associated with muscle growth and development. This study provides new insights to better understand the pathogenesis of VVD from an epigenetic perspective.

YAP Signaling in Glia: Pivotal Roles in Neurological Development, Regeneration and Diseases.

Yes-associated protein (YAP), the key transcriptional co-factor and downstream effector of the Hippo pathway, has emerged as one of the primary regulators of neural as well as glial cells. It has been detected in various glial cell types, including Schwann cells and olfactory ensheathing cells in the peripheral nervous system, as well as radial glial cells, ependymal cells, Bergmann glia, retinal Müller cells, astrocytes, oligodendrocytes, and microglia in the central nervous system. With the development of neuroscience, understanding the functions of YAP in the physiological or pathological processes of glia is advancing. In this review, we aim to summarize the roles and underlying mechanisms of YAP in glia and glia-related neurological diseases in an integrated perspective.

Yigu decoction regulates plasma miRNA in postmenopausal osteoporosis patients: a randomized controlled trial

BackgroundPostmenopausal osteoporosis (PMOP) is a serious condition that affects elderly individuals. Our previous study revealed that Yigu decoction (YGD) effectively improved bone mineral density (BMD) in elderly individuals, but the mechanism underlying this effect remains unclear. In this study, we investigated the relationships among YGD, microRNAs (miRNAs), and bone metabolism by assessing the effects of YGD on the miRNA levels in patient plasma to provide a scientific basis for treating PMOP with YGD.MethodsIn this clinical trial, 60 patients were randomly assigned to the YGD group or the control group (ratio of 1:1) and treated for 3 months. The primary outcome measure was BMD, and the secondary outcome measures included plasma miRNA levels, visual analogue scale (VAS) scores, alkaline phosphatase (ALP) levels, anti-tartrate acid phosphatase (TRACP-5b) levels and traditional Chinese medicine (TCM) syndrome scores. We assessed the regulatory roles of miRNAs in PMOP patients by analysing publicly available data from the Gene Expression Omnibus (GEO) database. Bioinformatics methods were also used to explore the mechanism by which YGD regulates miRNAs that are involved in bone metabolism.ResultsCompared with those before treatment, the BMD, ALP levels, TRACP-5b levels, TCM syndrome scores and VAS scores improved in both groups after 3 months of treatment (P &amp;lt; 0.05). A total of 82 miRNAs differed between the groups. After analysing data from the GEO database, we confirmed that miR-133a-3p is the key molecule that mediates the effects of YGD intervention on PMOP. GO analysis of key genes suggested that gene enrichment was more pronounced in response to hormones, cellular response to growth factor stimulation, and positive regulation of physiological and metabolic processes. KEGG analysis revealed that these genes were enriched mainly in the PI3K-Akt, FOXO, and JAK-STAT pathways and other pathways. The results of the protein‒protein interaction (PPI) network analysis revealed that epidermal growth factor receptor (EGFR), Insulin-like growth factor 1 (IGF-1), Caveolin-1 (Cav-1) and others were core proteins.ConclusionThis study demonstrated that YGD is beneficial in the treatment of PMOP, ameliorating clinical symptoms and bone turnover indices. Moreover, the inhibition of miR-133a-3p expression may be the key mechanisms by which YGD regulates bone metabolism in the treatment of PMOP, although YGD regulates bone metabolism in a multitarget and multipathway manner.

Extracellular Vesicles as Biomarkers of Pregnancy Complications

Extracellular vesicles (EVs) are double-membrane vesicles that facilitate intercellular communication and play a pivotal role in both physiological and pathological processes. A substantial body of evidence suggests that EVs play a role in the pathogenesis of various pregnancy complications. Because EVs can be detected in the peripheral blood, they are potential biomarkers for the early diagnosis of pregnancy complications and foetal developmental disorders. The majority of studies have demonstrated a correlation between alterations in the concentration of EVs and changes in their contents and the occurrence of pregnancy complications. Despite the current limitations in establishing a clear link between these findings and the pathogenesis of the disease, as well as the lack of sufficient evidence to support their use in clinical practice, it is noteworthy to highlight the potential role of specific miRNAs carried by EVs in the development of pregnancy complications. These include miR-210 and miR-136-5p for pre-eclampsia and gestational diabetes mellitus, miR-155, miR-26b-5p, miR-181a-5p, miR-495 and miR-374c for pre-eclampsia and preterm birth. The following miRNAs have been identified as potential biomarkers for preterm birth and gestational diabetes mellitus: miR-197-3p and miR-520h, miR-1323, miR-342-3p, miR-132-3p, miR-182-3p, miR-517-3p, miR-222-3p, miR-16-5p and miR-126-3p. Additionally, miR-127-3p has been linked to foetal growth restriction and preterm birth. Nevertheless, it would be premature to propose that EVs can be employed as biomarkers for pregnancy complications. Further research and the accumulation of results obtained using the methods proposed in the MISEV2023 guidelines will enable a definitive conclusion to be reached.

Unlocking the therapeutic potential and personalized therapy of testosterone: a comprehensive review.

Testosterone, the primary male sex hormone, orchestrates various physiological processes including sex differentiation, development of male characteristics, sperm production, and fertility. Its synthesis primarily occurs in Leydig cells within the testes, with smaller contributions from the ovaries and adrenal glands, all derived from cholesterol. Current therapeutic use of testosterone is mainly confined totreating hypergonadotropic hypogonadism, with limited off-label usage for augmenting muscle growth. This review delves into numerous studies investigating testosterone's therapeutic potential across various medical conditions as depicted in the figure given below. Of all the studies in this review, which show a positive therapeutic result by using testosterone, the most promising areas of potential usage of testosterone are anxiety and diabetes mellitus, followed by obesity and depression. By the medium if this study, we want to not only enlist the various potential therapeutic uses of testosterone, butalso promote a optimal hormonal balance, which can lead toprevention and/or better treatment outcomes for the mentioned diseases.

An AIE fungal vacuole membrane probe toward species differentiation, vacuole formation visualization, and targeted photodynamic therapy

Vacuoles are unique organelles of fungi. The development of probes targeting the vacuoles membrane will enable visualization of physiological processes and precise diagnosis and therapy. Herein, a zwitterionic molecule, MXF-R, comprising of an aggregation-induced emission (AIE) photosensitizing unit and an antibiotic moxifloxacin, was found capable of specifically imaging vacuole membrane and using for targeted antifungal therapy. MXF-R demonstrated a higher signal-to-noise ratio, stronger targeting capability, and better biocompatibility than the commercial probe FM4-64. By using MXF-R, real-time visualization of vacuole formation during Candida albicans (C. albicans) proliferation was achieved. More importantly, owing to its varying staining ability towards different fungus, MXF-R could be used to quickly identify C. albicans in mixed strains by fluorescence imaging. Moreover, MXF-R exhibits a remarkable ability to generate reactive oxygen species under white light, effectively eradicating C. albicans by disrupting membrane structure. This antifungal therapy of membrane damage is more effective than clinical drug fluconazole. Therefore, this work not only presents the initial discovery of a probe targeting vacuolar membrane, but also provides a way to develop novel materials to realize integrated diagnosis and therapy.