Regulation Function Research Articles

Exploring the Frontiers of Cell Temperature Measurement and Thermogenesis.

The precise measurement of cell temperature and an in-depth understanding of thermogenic processes are critical in unraveling the complexities of cellular metabolism and its implications for health and disease. This review focuses on the mechanisms of local temperature generation within cells and the array of methods developed for accurate temperature assessment. The contact and noncontact techniques are introduced, including infrared thermography, fluorescence thermometry, and other innovative approaches to localized temperature measurement. The role of thermogenesis in cellular metabolism, highlighting the integral function of temperature regulation in cellular processes, environmental adaptation, and the implications of thermogenic dysregulation in diseases such as metabolic disorders and cancer are further discussed. The challenges and limitations in this field are critically analyzed while technological advancements and future directions are proposed to overcome these barriers. This review aims to provide a consolidated resource for current methodologies, stimulate discussion on the limitations and challenges, and inspire future innovations in the study of cellular thermodynamics.

Therapeutic mechanism and key active ingredients of Yinxing Mihuan Oral Solution in coronary heart disease comorbidity with anxiety: A network pharmacology and molecular docking approach.

Yinxing Mihuan Oral Solution (YMOS) is a Chinese patent medicine for treating coronary heart disease combined anxiety (CHDCA), but the molecular mechanism of its treatment is still unclear. This article aims to understand the molecular mechanism, optimize clinical drug use, and guide new drug development. Using the Swiss Target Prediction database, we obtained the main chemical composition of YMOS. Then we used network pharmacology to identify their potential targets. Network construction, coupled with protein-protein interaction and enrichment analysis was used to identify representative components and core targets. Finally, molecular docking simulation was conducted to further refine the drug-target interaction. Forty-two active chemicals were found in YMOS and 91 target genes related to CHDCA. The treatment effect was found to be associated with 1908 biological processes and 160 pathways, as revealed by the outcomes of the enrichment analysis. The potential therapeutic mechanisms of the drug are closely related to its antioxidant, anti-inflammatory, and vascular function regulation pathways, and the main core targets include albumin, tumor necrosis factor, TP53, AKT serine/threonine kinase 1, interleukin 1 beta, and vascular endothelial growth factor A. The potential molecular mechanisms of YMOS in CHDCA treatment were identified using network pharmacology and molecular docking approaches. The results reveal the systemic biological implications of YMOS. This study has systematically uncovered the molecular mechanism of YMOS for the first time, offering fresh insights for evidence-based clinical applications.

Distribution Of Microrna Counts Across Human Chromosomes.

microRNAs (miRNAs) are a class of non-coding RNAs that play important roles in gene regulation. miRNAs are transcribed from DNA sequences into primary miRNAs and then processed into precursor miRNAs and mature miRNAs. miRNA gene counts in chromosomes for different species have been studied. Certain chromosomes have higher numbers of miRNA genes in all species, such as the X chromosome, while the Y chromosome has the fewest or no miRNA genes. miRNA counts in different chromosomes might have a positive correlation with coding gene counts in many species. In this study, a regression model was used to find the relationship between the miRNA count and the coding gene count across human chromosomes, and miRNA counts for 23 human chromosomes were predicted based on this regression model. In addition, the chromosome locations for the miRNA biomarkers of major depression, diabetes, Parkinson's disease, and COVID-19 are discussed. The results reveal that miRNA biomarkers of these diseases are located in various chromosomes. The dispersion of miRNA locations across different chromosomes might explain the complication of the pathology of these diseases. Moreover, diabetes and COVID-19 have the largest number of miRNA biomarkers from Chromosome X. As Chromosome X is a sex chromosome, this phenomenon may explain the gender difference in the prevalence or severity of diabetes and COVID-19. The significant gender difference in the prevalence or severity of diabetes and COVID-19 might be due to the regulation function of their miRNA biomarkers from Chromosome X.

Hypoxanthine Produces Rapid Antidepressant Effects by Suppressing Inflammation in Serum and Hippocampus.

The occurrence and development of depression are closely related to disorders of the brain and peripheral substances. Abnormal metabolites in the blood affect the signal regulation function of the nerve center, which is one of the key factors for depression episodes. This study was focused on metabolites in serum and the mechanism of its antidepressant in the hippocampus. In the present study, serum metabolites in patients with depression were screened by metabolomic techniques. Various depressive mouse models and behavioral tests were used to assess its antidepressant effects. The expressions of inflammatory signaling were detected by using Western blot, ELISA, and immunofluorescence. We found that the metabolite hypoxanthine in the serum of patients with depression was significantly reduced, and the same result was also found in two mouse models of depression such as chronic unpredictable mild stress (CUMS) and social defeat stress (SD). By administering different doses of hypoxanthine (5, 10, 15 mg/kg), we found that only 15 mg/kg was able to significantly reduce the latency and increase food consumption in the novelty suppressed-feeding test (NSF), which was also able to reverse the depressive phenotypes of mice in the CUMS model after a single administration at 2 h later. Hypoxanthine obviously reduced the expressions of inflammation in serum and downregulated the expressions of MAPK and NLRP3-related pathways in the hippocampus in CUMS mice. Moreover, hypoxanthine also suppressed the activations of glial cells including GFAP and IBA-1 in hippocampal CA1, CA3, and dentate gyrus (DG). To sum up, hypoxanthine exerted antidepressant effect relying on the inhibition of peripheral and hippocampal inflammations by regulating MAPK, NLRP3-related pathways, and glial cells. This was the first time that we have found a disordered metabolite in patients with depression and further systematically demonstrated its efficacy and potential mechanism of antidepressants, providing new ideas for antidepressant drug development.

Alterations of regional brain activity and corresponding brain circuits in drug-naïve adolescents with nonsuicidal self-injury

Nonsuicidal self-injury (NSSI) is one of the major public health problems endangering adolescents. However, the neural mechanisms of NSSI is still unclear. The purpose of this study was to explore regional brain activity and corresponding brain circuits in drug-naïve adolescents with NSSI using amplitude of low-frequency fluctuations (ALFF) combined with functional connectivity (FC) analysis. Thirty-two drug-naïve adolescents with NSSI (NSSI group) and 29 healthy controls matched for sex, age, and level of education (HC group) were enrolled in this study. ALFF and seed-based FC analyses were used to examine the alterations in regional brain activity and corresponding brain circuits. The correlation between ALFF or FC values of aberrant brain regions and clinical characteristics were detected by Pearson correlation analysis. The NSSI group showed increased ALFF in the left inferior and middle occipital gyri, lingual gyrus, and fusiform gyrus; additionally, decreased ALFF in the right medial cingulate gyrus, left anterior cingulate gyrus, and left medial superior frontal gyrus compared to those in the HC group. With the left inferior occipital gyrus as seed, the NSSI group showed increased FC between the left inferior occipital gyrus and the bilateral superior parietal gyrus, right inferior parietal angular gyrus, right inferior frontal gyrus of the insular region, and left precuneus relative to that the HC group. With the left anterior cingulate gyrus as seed, the NSSI group showed increased FC between the left anterior cingulate gyrus and right dorsolateral superior frontal gyrus. With the left lingual gyrus as seed, the NSSI group showed increased FC between the left lingual gyrus and right middle frontal gyrus, and decreased FC between the left lingual gyrus and the left superior temporal gyrus, right supplementary motor area, and left rolandic operculum. With the left fusiform gyrus as seed, the NSSI group showed increased FC between the left fusiform gyrus and left middle and inferior temporal gyrus, and decreased FC between the left fusiform gyrus and the bilateral postcentral gyrus, right precentral gyrus, right lingual gyrus, and left inferior parietal angular gyrus. Moreover, the FC value between the left fusiform gyrus and left inferior temporal gyrus was positively correlated with suicidal ideations score. This study highlights alterations in regional brain activity and corresponding brain circuits in brain regions related to visual and emotional regulation functions in drug-naïve adolescents with NSSI. These findings may facilitate better understand the underlying neural mechanisms of NSSI in adolescents.

Expression of Molecules Characterizing Metabolic and Cytotoxic Activity of Natural Killer Different Subpopulations of Peripheral Blood During Pregnancy

The functions of peripheral blood NK cells change significantly during pregnancy, which is mainly due to the inhibition of their cytotoxicity. The functional activity of NK cells is directly related to their metabolic status, but these changes in physiological pregnancy have not been studied. The aim of this work is to study the expression of Glut-1, CD94 and CD107a molecules characterizing metabolic and cytotoxic activity, as well as the mitochondrial mass of different subpopulations of peripheral blood NK cells in the I and III trimesters of physiological pregnancy. The object of the study was the peripheral blood of healthy women in the I and III trimesters of physiological pregnancy. The control group consisted of healthy non-pregnant women in the follicular phase of the menstrual cycle. The expression of Glut-1, CD94, CD107a molecules and the mitochondrial mass were analyzed by flow cytometry on regulatory (CD16–CD56bright), cytotoxic (CD16+CD56dim), minor cytotoxic (CD16hiCD56–) NK cells. It was found that in non-pregnant women, minor cytotoxic CD16hiCD56–NK have the highest expression of Glut-1, CD107a and the lowest expression of CD94 compared to other NK cell subpopulations. On regulatory CD16–CD 56bright and cytotoxic CD16+CD56dimNK, the expression of these molecules is comparable to each other. The mitochondrial mass is similar in all studied subpopulations. In the first trimester, the expression of Glut-1 increases on regulatory CD16–CD56brightNK, the mitochondrial mass and the expression of CD94, CD107a in all NK cells do not differ from non-pregnant ones. In the third trimester, the mitochondrial mass increases in cytotoxic CD16+CD56dimNK cells, but CD94 expression decreases compared to non-pregnant ones, and the expression CD94 in regulatory CD16–CD56brightNK increases compared to the first trimester. CD107a expression in minor cytotoxic CD16hiCD56–NK decreases, but in other subpopulations does not change compared to non-pregnant. The expression of Glut-1 does not change in all subpopulations. Thus, different subpopulations of peripheral blood NK cells are heterogeneous in the expression of Glut-1, CD107a, CD94. The expression of these molecules during physiological pregnancy varies by trimester. The obtained results are important for understanding the mechanisms of NK cell function regulations during pregnancy.

Pancreatic β-Cells, Diabetes and Autophagy.

Pancreatic β-cells play a critical role in regulating plasma insulin levels and glucose metabolism balance, with their dysfunction being a key factor in the progression of diabetes. This review aims to explore the role of autophagy, a vital cellular self-maintenance process, in preserving pancreatic β-cell functionality and its implications in diabetes pathogenesis. We examine the current literature on the role of autophagy in β-cells, highlighting its function in maintaining cell structure, quantity, and function. The review also discusses the effects of both excessive and insufficient autophagy on β-cell dysfunction and glucose metabolism imbalance. Furthermore, we discuss potential therapeutic agents that modulate the autophagy pathway to influence β-cell function, providing insights into therapeutic strategies for diabetes management. Autophagy acts as a self-protective mechanism within pancreatic β-cells, clearing damaged organelles and proteins to maintain cellular stability. Abnormal autophagy activity, either overactive or deficient, can disrupt β-cell function and glucose regulation, contributing to diabetes progression. Autophagy plays a pivotal role in maintaining pancreatic β-cell function, and its dysregulation is implicated in the development of diabetes. Targeting the autophagy pathway offers potential therapeutic strategies for diabetes management, with agents that modulate autophagy showing promise in preserving β-cell function.

Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.

Viral infections are increasingly recognized as triggers for depressive disorders, particularly following the SARS-CoV-2 pandemic and the rise of long COVID. Viruses such as Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Human Immunodeficiency Virus (HIV) are linked to depression through complex neurobiological mechanisms. These include immune system dysregulation, chronic inflammation, and neurotransmitter imbalances that affect brain function and mood regulation. Viral activation of the immune system leads to the release of pro-inflammatory cytokines, resulting in neuroinflammation and associated depressive symptoms. Furthermore, specific viruses can disrupt neurotransmitter systems, including serotonin, dopamine, and glutamate, all of which are essential for mood stabilization. The unique interactions of different viruses with these systems underscore the need for virus-specific therapeutic approaches. Current broad-spectrum treatments often overlook the precise neurobiological pathways involved in post-viral depression, reducing their efficacy. This review emphasizes the need to understand these virus-specific interactions to create tailored interventions that directly address the neurobiological effects induced by each type of virus. These interventions may include immunomodulatory treatments that target persistent inflammation, antiviral therapies to reduce the viral load, or neuroprotective strategies that restore neurotransmitter balance. Precision medicine offers promising avenues for the effective management of virus-induced depression, providing patient-specific approaches that address the specific biological mechanisms involved. By focusing on the development of these targeted treatments, this review aims to pave the way for a new era in psychiatric care that fully addresses the root causes of depression induced by viral infections.

The impact of immersive virtual reality meditation for depression and anxiety among inpatients with major depressive and generalized anxiety disorders.

Mindfulness-Based Cognitive Therapy (MBCT) is a non-pharmacological approach to alleviating depression and anxiety. While technology based MBCT is a standardized cost-effective approach, there have been concerns about its feasibility and effectiveness in clinical settings. The purpose of this study was to investigate the longitudinal relationship between improved emotional regulation resulting from participation in Immersive Virtual Reality Meditation (IVRM) and Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) as monitored by electrocardiogram. This study was a longitudinal single-arm clinical trial in which the intervention was conducted three times a week for 10 weeks at a behavioral health unit in a community hospital (n = 26). We measured Coherence Achievement Score (CAS), depression, and anxiety. The relationships between CAS, anxiety, depression, and covariates were analyzed using a Generalized Estimated Equation (GEE). The findings of our study provide evidence that the CAS scores indicative of emotional regulation function after IVRM participation were associated with a reduction in depression and anxiety. Among the many technology-based complementary health care interventions that are available to reduce depression and anxiety, IVRM program use increases emotional regulatory function and decrease depression and anxiety.

Regulation of Mitochondrial and Peroxisomal Metabolism in Female Obesity and Type 2 Diabetes.

Obesity and type 2 diabetes (T2D) are widespread metabolic disorders that significantly impact global health today, affecting approximately 17% of adults worldwide with obesity and 9.3% with T2D. Both conditions are closely linked to disruptions in lipid metabolism, where peroxisomes play a pivotal role. Mitochondria and peroxisomes are vital organelles responsible for lipid and energy regulation, including the β-oxidation and oxidation of very long-chain fatty acids (VLCFAs), cholesterol biosynthesis, and bile acid metabolism. These processes are significantly influenced by estrogens, highlighting the interplay between these organelles' function and hormonal regulation in the development and progression of metabolic diseases, such as obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), and T2D. Estrogens modulate lipid metabolism through interactions with nuclear receptors, like peroxisome proliferator-activated receptors (PPARs), which are crucial for maintaining metabolic balance. Estrogen deficiency, such as in postmenopausal women, impairs PPAR regulation, leading to lipid accumulation and increased risk of metabolic disorders. The disruption of peroxisomal-mitochondrial function and estrogen regulation exacerbates lipid imbalances, contributing to insulin resistance and ROS accumulation. This review emphasizes the critical role of these organelles and estrogens in lipid metabolism and their implications for metabolic health, suggesting that therapeutic strategies, including hormone replacement therapy, may offer potential benefits in treating and preventing metabolic diseases.

Functional and transcriptional regulation of the anthocyanidin acyl modifier gene Gs5AT of Gentiana sino-ornata.

The Chinese gentian, Gentiana sino-ornata produces brilliant blue flowers. To investigate the biological function and transcriptional regulation mechanism of the anthocyanin 5-O-acyltransferase gene (Gs5AT ) in the corolla, it is beneficial to analyse the mechanism of blue flower colour presentation. In this investigation, we obtained the CDS and promoter sequences of the gene Gs5AT . Yeast one-hybrid experiments were used to identify the transcription factor GsbHLH7 that activates the gene Gs5AT . According to quantitive reverse transcription polymerase chain reaction analysis, the expression of the gene Gs5AT was significantly and positively correlated with the gene GsbHLH7 . The colour phenotype of the flowers was significantly altered by the virus-induced gene silencing transduction of Gs5AT and GsbHLH7 , with GsbHLH7 silencing producing more pronounced changes in the corolla colour than Gs5AT . The expression of GsF3'5'H , GsDFR , GsANS , Gs3GT , and Gs5GT all fell to varying degrees after GsbHLH7 silencing, indicating that GsbHLH7 may regulate transcription of these genes as well as Gs5AT . The results of this study indicate that Gs5AT was positively regulated by the GsbHLH7 , and thus affects the colour presentation of the blue corolla.

Effect of Aeromonas hydrophila infection on leptin receptor overlapping transcript expression in Rana amurensis

The leptin receptor overlapping transcript (LepROT) has been suggested to play several roles in immunomodulatory mechanisms; however, the understanding of its role in Rana amurensis immunity is still very limited. Here, we performed hematoxylin-eosin staining, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunofluorescence and western blotting to investigate the roles of LepROT in the immunomodulatory mechanism and the influence of its expression on the nuclear factor-kappa B (NF-κB) signaling pathway, such as the activation of IκB kinase and NF-кB, in amphibian resistance to infection with Aeromonas hydrophila (Ah). After Ah infection, the liver, lung, kidney, skin, muscle, and stomach of R. amurensis showed cell structure disturbance, bleeding, and texture abnormalities. In addition, the relative expression levels of LepROT, NF-кB, IKKα, and IKKβ were all upregulated after Ah infection; however, they showed time-dependent differential expression. The NF-кB signaling pathway exhibited robust expression levels, which might be explained by the positive feedback regulation function of LepROT. Overall, this study provides a basis for further assessment of the biological functions of LepROT and highlights its role in the regulation of immune mechanisms.

Sports Development Management in the Republic of Armenia: The Structure and Statistics

Sports is one of the many branches of the national economic complex and represents a complex and unique socio-economic system, the activity of which is characterized by multifaceted social and state relations. It should be considered that the management structure of any socio-economic sector of the state is largely determined first by the state policy, the very structure of the state. It should be organically integrated into the sports movement management system. The state body responsible for the development of sports in Republic of Armenia (RA) is the Ministry of Education, Science, Culture and Sports (MESCS), which is entrusted with the functions of implementing state policy and legal regulation, as well as providing support to sports organizations and sports federations. The main goal of its activity is the formation of a positive attitude of society, the state and the entire nation towards sports as an effective means of maintaining and strengthening human health, an integral part of universal culture, and as a factor, especially in the physical and moral education of children and young people. The Ministry carries out the functions of state policy and legal regulation in physical culture, sports and youth issues and the processes of developing and implementing them. Along with that, public sports organizations in the form of NAOC of Armenia and national sports federations and units play an important role in the development of sports in the republic. Funding for mass sports and high-performance sports is increasing year by year in Armenia, which is aimed at increasing the number of events, as well as increasing the number of incentives for the achievements of people who do sports and high-level athletes.

Axonal Energy Crisis and Calcium Phosphate Dysregulation as Pathogenesis of Optic Disc Drusen.

Soft tissue ectopic calcification is due to abnormal accumulation of calcium and phosphate outside the bone. It is the result of the failure of a complex, active, and highly regulated process - much of which is still not well understood. Some of our understanding of ectopic calcification come from studies on diseases such as atherosclerosis, aortic valve disease and kidney stone disease. In the eye, the most common causes of visual defects due to ectopic calcification include optic disc drusen (ODD) and age-related macular degeneration (AMD). In ODD, ectopic calcification occurs only in the most anterior, unmyelinated portion of optic nerve - the sole output of the eye and particularly susceptible to hypoxic and metabolic stress. In this article, we review the effects of hypoxia on mitochondrial function and calcium regulation and delineate the key processes likely involved in ectopic calcification. We propose a working hypothesis for ODD centering on the role of hypoxia-induced calcium and phosphate overload, mitochondrial dysfunction and osteogenic differentiation, leading to hydroxyapatite deposition and biomineralization.

Spatial and functional separation of mTORC1 signalling in response to different amino acid sources.

Amino acid (AA) availability is a robust determinant of cell growth through controlling mechanistic/mammalian target of rapamycin complex 1 (mTORC1) activity. According to the predominant model in the field, AA sufficiency drives the recruitment and activation of mTORC1 on the lysosomal surface by the heterodimeric Rag GTPases, from where it coordinates the majority of cellular processes. Importantly, however, the teleonomy of the proposed lysosomal regulation of mTORC1 and where mTORC1 acts on its effector proteins remain enigmatic. Here, by using multiple pharmacological and genetic means to perturb the lysosomal AA-sensing and protein recycling machineries, we describe the spatial separation of mTORC1 regulation and downstream functions in mammalian cells, with lysosomal and non-lysosomal mTORC1 phosphorylating distinct substrates in response to different AA sources. Moreover, we reveal that a fraction of mTOR localizes at lysosomes owing to basal lysosomal proteolysis that locally supplies new AAs, even in cells grown in the presence of extracellular nutrients, whereas cytoplasmic mTORC1 is regulated by exogenous AAs. Overall, our study substantially expands our knowledge about the topology of mTORC1 regulation by AAs and hints at the existence of distinct, Rag- and lysosome-independent mechanisms that control its activity at other subcellular locations. Given the importance of mTORC1 signalling and AA sensing for human ageing and disease, our findings will probably pave the way towards the identification of function-specific mTORC1 regulators and thus highlight more effective targets for drug discovery against conditions with dysregulated mTORC1 activity in the future.

Development and safety of investigational and approved drugs targeting the RAS function regulation in RAS mutant cancers.

The RAS gene family holds a central position in controlling key cellular activities such as migration, survival, metabolism, and other vital biological processes. The activation of RAS signaling cascades is instrumental in the development of various cancers. Although several RAS inhibitors have gained approval from the United States Food and Drug Administration (FDA) for their substantial antitumor effects, their widespread and severe adverse reactions significantly curtail their practical usage in the clinic. Thus, there exists a pressing need for a comprehensive understanding of these adverse events, ensuring the clinical safety of RAS inhibitors through the establishment of precise management guidelines, suitable intermittent dosing schedules, and innovative combination regimens. This review centers on the evolution of RAS inhibitors in cancer therapy, delving into the common adverse effects associated with these inhibitors, their underlying mechanisms, and the potential strategies for mitigation.

Ethionine-induced S-adenosylmethionine deficiency suppressed H3K27me3 and cell differentiation during neural tube development in mice.

S-adenosylmethionine (SAM) as a major methyl donor plays a key role in methylation modification in vivo, and its disorder was closely related to neural tube defects (NTDs). However, the exact mechanism between SAM deficiency and NTDs remained unclearly. Hence, we investigated the association between histone methylation modification and cell differentiation in NTDs mice induced by SAM deficiency. The levels of SAM and SAH (S-adenosylhomocysteine) were determined by enzyme linked immunosorbent assay (ELISA). The level of histone methylation, β-catenin were analyzed by Western blot, reversing transcription and quantitative PCR (RT-qPCR) and immunofluorescence. The results showed that the incidence rate of NTDs induced by ethionine were 46.2%. Post treatment of ethionine combined with SAM, the incidence rate of NTDs was reduced to 26.2%. The level of SAM was significantly decreased (p < 0.05) and a reduction in the SAM/SAH ratio was observed after entionine treatment. The SAM deficiency caused the reduction of H3K27me3 modifications and the elevated UTX activity (p < 0.05), and inhibited the expressions of β-catenin. The differentiations of NSCs into neurons and oligodendrocytes were inhibited under SAM deficiency (p < 0.05). These results indicated that the SAM deficiency led to reduce H3K27me3 modifications, prevented the β-catenin signaling pathway and NSCs differentiation, which provided an understanding of the novel function of epigenetic regulation in NTDs.

Multifaceted natural drought response mechanisms in three elite date palm cultivars uncovered by expressed sequence tags analysis.

This study extends our prior research on drought responses in three date palm cultivars (Khalas, Reziz, and Sheshi) under controlled conditions. Here, we investigated their drought stress adaptive strategies under ambient environment. Under natural field drought conditions, three date palm cultivars experienced significantly (p ≤ 0.05) varying regulations in their physiological attributes. Specifically, chlorophyll content, leaf RWC, photosynthesis, stomatal conductance, and transpiration reduced significantly, while intercellular CO2 concentration and water use efficiency increased. Through suppression subtraction hybridization (SSH), a rich repertoire (1026) of drought-responsive expressed sequence tags (ESTs) were identified: 300 in Khalas, 343 in Reziz, and 383 in Sheshi. Functional analysis of ESTs, including gene annotation and KEGG pathways elucidation, unveiled that these cultivars withstand drought by leveraging indigenous and multifaceted pathways. While some pathways aligned with previously reported drought resilience mechanism observed under controlled conditions, several new indigenous pathways were noted, pinpointing cultivar-specific adaptations. ESTs identified in three date palm cultivars were enriched through GSEA analysis. Khalas exhibited enrichment in cellular and metabolic processes, catalytic activity, and metal ion binding. Reziz showed enrichment in biological regulation, metabolic processes, signaling, and nuclear functions. Conversely, Sheshi displayed enrichment in organelle, photosynthetic, and ribosomal components. Notably, ca. 50% of the ESTs were unique and novel, underlining the complexity of their adaptive genetic toolkit. Overall, Khalas displayed superior drought tolerance, followed by Reziz and Sheshi, highlighting cultivar-specific variability in adaptation. Conclusively, date palm cultivars exhibited diverse genetic and physiological strategies to cope with drought, demonstrating greater complexity in their resilience compared to controlled settings.

Characterizing metabolomic and transcriptomic changes, and investigating the therapeutic mechanism of Psoralea corylifolia linn. In the treatment of kidney-yang deficiency syndrome in rats

Kidney-yang deficiency syndrome (KYDS) is characterized by a metabolic disorder stemming from neuroendocrine dysregulation, often associated with hepatic dysfunction. In traditional Chinese medicine, Psoralea corylifolia Linn. (BGZ) is commonly utilized for treating KYDS. However, the specific therapeutic effects of BGZ on liver function regulation remain unclear. To evaluate the protective effects of BGZ against KYDS in rats, organ index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other biochemical indices were analyzed. Hematoxylin and eosin (HE) staining was utilized to assess liver histopathology. Additionally, transcriptomic and metabolomic analyses were conducted to identify potential biomarkers. BGZ treatment led to a significant reduction in ALT and AST levels, accompanied by improvements in liver histopathology in rats with KYDS. Moreover, BGZ induced significant alterations in 92 differentially expressed genes (DEGs) and 20 metabolites in the KYDS rat model. The comprehensive examination of metabolites and DEGs identified potential mechanisms underlying the therapeutic effects of BGZ, highlighting the neuroactive ligand-receptor interaction, cAMP signaling pathway, calcium signaling pathway, and cytokine-cytokine receptor interaction as key mechanisms. Validation of key targets within the cAMP pathway was substantiated through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. The cAMP pathway emerges as a plausible mechanism through which BGZ exerts protective effects against KYDS. The findings of this study contribute to an improved understanding of the therapeutic actions of BGZ and establish a groundwork for further research into the complex pathways involved, as well as the potential for drug-targeted therapies for KYDS.

Dietary supplement guava leaf extract regulates growth, feed utilization, immune function, nutrient digestibility and redox regulation in growing rabbits

The use of agricultural waste in animal production has gained global interest. An eight-week trial was conducted to investigate the impacts of adding ethanolic guava leaf extract (GLE) as a feed supplement on the growth, feed utilization, immune response, nutrient digestibility, redox regulation, and blood health of growing rabbits. Ninety weaned growing rabbits were randomly assigned to three groups. The first group was fed a basal diet (GLE0), while the other two groups were fed the control diet fortified with 15 mg (GLE15) or 20 mg (GLE20) of GLE per kg of diet for 8 weeks. The HPLC analysis of GLE exhibited the presence of gallic acid, ferulic acid, catechin, and caffeic acid in significant amounts. The results indicated that final body weight, daily body weight, daily feed intake and nutrient digestibility were significantly higher in the GLE-treated groups compared to the un-treated group (p < 0.05). Dietary supplementation of GLE significantly reduced lipid contents including triglycerides, total cholesterol, LDL, HDL, and VLDL (P < 0.05), with the most significant results observed when adding 20 mg/kg to the diet. AST and ALT levels as well as cortisol hormone in rabbits fed GLE were lower than those in the GLE0 group (P < 0.05). Immunoglobulins (IgG and IgA), antioxidant biomarkers (SOD and TAC) and T3 hormone were significantly improved by GLE supplementation (P < 0.001). Rabbits fed with GLE had lower levels of ROS and MDA compared to those in the GLE0 group (P < 0.001). Moreover, the hepatic and intestinal architectures were maintained in all rabbits fed diets with GLE. The results suggest that GLE supplementation (20 mg/kg diet) in fattening rabbit diets could efficiently improve growth, health status, blood physiology, antioxidant capacity and tissue histology.