Abnormal Secretion Research Articles

Intestinal lysozyme engagement of Salmonella Typhimurium stimulates the release of barrier-impairing InvE and Lpp1

Lysozyme is a β-1,4-glycosidase that hydrolyzes the polysaccharide backbone of bacterial cell walls. With an additional bactericidal function mediated by a separate protein domain, lysozyme is considered a uniquely important antimicrobial molecule contributing to the host's innate immune response to infection. Elevated lysozyme production is found in various inflammatory conditions while patients with genetic risks for inflammatory bowel diseases demonstrate abnormal lysozyme expression, granule packaging, and secretion in Paneth cells. However, it remains unclear how a gain- or loss-of-function in host lysozyme may impact the host inflammatory responses to pathogenic infection. We challenged Lyz1-/- and ectopic Lyz1-expressing (Villin-Lyz1TG) mice with S. Typhimurium and then comprehensively assessed the inflammatory disease progression. We conducted proteomics analysis to identify molecules derived from human lysozyme-mediated processing of live Salmonella. We examined the barrier-impairing effects of these identified molecules in human intestinal epithelial cell monolayer and enteroids. Lyz1-/- mice are protected from infection in terms of morbidity, mortality, and barrier integrity, whereas Villin-Lyz1TG mice demonstrate exacerbated infection and inflammation. The growth and invasion of Salmonella invitro are not affected by human or chicken lysozyme, whereas lysozyme encountering of live Salmonella stimulates the release of barrier-disrupting factors, InvE-sipC and Lpp1, which directly or indirectly impair the tight junctions. The direct engagement of host intestinal lysozyme with an enteric pathogen such as Salmonella promotes the release of virulence factors that are barrier-impairing and pro-inflammatory. Controlling lysozyme function may help alleviate the inflammatory progression.

Assembled pH-Responsive Gastric Drug Delivery Systems Based on 3D-Printed Shells.

Gastric acid secretion is closely associated with the development and treatment of chronic gastritis, gastric ulcers, and reflux esophagitis. However, gastric acid secretion is affected by complex physiological and pathological factors, and real-time detection and control are complicated and expensive. A gastric delivery system for antacids and therapeutics in response to low pH in the stomach holds promise for smart and personalized treatment of stomach diseases. In this study, pH-responsive modular units were used to assemble various modular devices for self-regulation of pH and drug delivery to the stomach. The modular unit with a release window of 50 mm2 could respond to pH and self-regulate within 10 min, which is related to its downward floatation and internal gas production. The assembled devices could stably float downward in the medium and detach sequentially at specific times. The assembled devices loaded with antacids exhibited smart pH self-regulation under complex physiological and pathological conditions. In addition, the assembled devices loaded with antacids and acid suppressors could multi-pulse or prolong drug release after rapid neutralization of gastric acid. Compared with traditional coating technology, 3D printing can print the shell layer by layer, flexibly adjust the internal and external structure and composition, and assemble it into a multi-level drug release system. Compared with traditional coating, 3D-printed shells have the advantage of the flexible adjustment of internal and external structure and composition, and are easy to assemble into a complex drug delivery system. This provides a universal and flexible strategy for the personalized treatment of diseases with abnormal gastric acid secretion, especially for delivering acid-unstable drugs.

The TLR4/NF-κB/NLRP3 and Nrf2/HO-1 pathways mediate the neuroprotective effects of alkaloids extracted from Uncaria rhynchophylla in Parkinson's disease

Ethnopharmacological relevanceParkinson's disease (PD) is the second most common neurodegenerative disorder with limited therapeutic options available. Neuroinflammation plays an important role in the occurrence and development of PD. Alkaloids extracted from Uncaria rhynchophylla (URA), have emerged as a potential neuroprotective agent because of its anti-inflammatory and anti-oxidant properties. Nevertheless, the underlying mechanism by which URA exerts neuroprotective effects in PD remains obscure. Aim of the studyThe main aim of this study was to investigate the neuroprotective effects and underlying mechanism of URA in the treatment of PD through in vivo and in vitro models, focusing on the neuroinflammation and oxidative stress pathways. Materials and methodsThe protective effects of URA against PD were evaluated by neurobehavioral tests, immunohistochemistry, serum biochemical assays, and real-time quantitative polymerase chain reaction in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. The role of the TLR4/NF-κB/NLRP3 pathway and the Nrf2/HO-1 pathway in URA-mediated effects was examined in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and a microglia-neuron coculture system. ResultsURA significantly alleviated motor deficits and dopaminergic neurotoxicity, and reversed the abnormal secretion of inflammatory and oxidative stress factors in the serum of MPTP-induced mice. URA suppressed the gene expression of Toll-like receptor 4 (TLR4), NOD-like receptor protein 3, and cyclooxygenase 2 (COX2) in the striatum of PD mice. Further studies indicated that URA inhibited activation of the TLR4/NF-κB/NLRP3 pathway and enhanced activation of the Nrf2/HO-1 pathway, reduced reactive oxygen species (ROS) production, and reversed the secretion of inflammatory mediators in LPS-stimulated BV-2 microglial cells, thereby alleviating neuroinflammatory damage to SH-SY5Y neuronal cells. ConclusionURA exerted neuroprotective effects against PD mainly by the inhibition of the TLR4/NF-κB/NLRP3 pathway and activation of the Nrf2/HO-1 antioxidant pathway, highlighting URA as a promising candidate for PD treatment.

Lab on the Microneedles: A Wearable Metal-organic Frameworks-Based Sensor for Visual Monitoring of Stress Hormone.

Abnormal secretion and dysrhythmias of cortisol (CORT) are associated with various diseases such as sleep disorders, depression, and chronic fatigue. Wearable devices are a cutting-edge technology for point-of-care detection and dynamic monitoring of CORT with inspiring convenience. Herein, we developed a minimally invasive skin-worn device with the advanced integration of both interstitial fluid (ISF) sampling and target molecule sensing for simultaneous detection of CORT via a microneedle-based sensor with high sensitivity, excellent efficiency, and outstanding reproducibility. In the microneedle patch, swellable hydrogel was employed as the adsorption matrix for ISF extraction. Meanwhile, europium metal-organic frameworks (Eu-MOF) wrapped in the matrix played a vital role in CORT recognition and quantitative analysis. The wearable and label-free Eu-MOF-loaded microneedle patch exhibited high sensitivity in CORT detection with the detection limit reaching 10-9 M and excellent selectivity. Molecular dynamics simulation-driven mechanism exploration revealed that the strong interface interaction promoted fluorescence quenching of Eu-MOF. Moreover, in vitro and in vivo investigation confirmed the feasibility and reliability of the sensing method, and excellent biocompatibility was validated. Overall, a sensitive approach based on the wearable Eu-MOF microneedle (MN) patch was established for the simultaneous detection of CORT via visible fluorescence quenching with exciting clinical-translational ability.

EDUCATION ABOUT DIET MANAGEMENT OF DIABETES MELLITUS TO ELDERLY AT THE ELDERLY POSYANDU, PELEM VILLAGE, KEDIRI DISTRICT

Diabetes Mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia due to abnormalities in insulin secretion, insulin action or both. The number of DM sufferers globally increases every year, the causes include increasing population, age, obesity, and lack of physical activity. Preventive measures that can be taken include education and regular health checks. To increase knowledge and understanding of elderly about hypertension and diabetes, one of the efforts made is to provide health education about hypertension and diabetes, as well as screening elderly in Pelem Village, Kediri District. In this activity, the results showed that there was increasing knowledge about diabetes of elderly, which was the addition of information and insight about health and provided a clear description for elderly regarding the prevention and management of diabetes through counseling and educational media in the form of leaflets.

The Benson Relaxation Technique The Effect Of The Benson Relaxation Technique On Sugar Blood Levels Blood In Type 2 Diabetes Mellitus Patients At Tangerang District Hospital

Introduction: Diabetes Mellitus (DM) is a group of metabolic disorders characterized by an increase in blood glucose levels (hyperglycemia) caused by abnormalities in insulin secretion, insulin action, or both. A nonpharmacological therapy that can be used as a companion to pharmacological therapy is Benson's relaxation technique. Benson's relaxation technique produces a relaxed state so that it can suppress hormones that cause blood sugar levels to rise such as epinephrine, cortisol, glucagon, ACTH corticosteroids, and thyroid. Objective: This study was to determine the effect of Benson's relaxation technique on blood sugar levels in Type 2 Diabetes Mellitus patients. Method: The research design used experimental queasy, with one group pretest-posttest design. The sampling technique in this study used purposive sampling with a total sample of 28 respondents conducted from April 13 to April 29, 2023, in the inpatient room of the Tangerang Regency Regional General Hospital. Then the data of this study was analyzed using paired t-tests. Results: Average GDS value before intervention 306.25 mg/dl and after intervention 276.57 mg/dl with p-value = 0.000 (<0.05). Conclusion: In this study, there was an effect of Benson's relaxation technique on reducing blood sugar levels in Diabetes Mellitus patients.

Pola penggunaan obat anti diabetes mellitus tipe-II pada pasien rawat inap di RSUD Praya tahun 2021

Diabetes mellitus is a metabolic disease characterized by hyperglycemia due to abnormalities in insulin secretion. The prevalence of people with diabetes mellitus in Indonesia reached 6.2% per year in 2020 and ranks 7th in the world with 8.5 million people. Based on the results of observations at the Praya Hospital in 2021, type-II diabetes mellitus is the 4th highest-order disease suffered by the community, especially Central Lombok Regency, with a total incidence of 131 patients. This study aims to determine the pattern of drug use and HbA1c profile in patients with type-II diabetes mellitus in the inpatient installation of Praya Hospital in 2021. This study was retrospective, using the Nonprobability Sampling method, namely the type of purposive sampling so that a sample of 96 medical records of diabetes mellitus patients was obtained type-II. The data is presented as pie charts and tables in percentages, which were analyzed using Microsoft Excel and SPSS version 25. From the results of this research, it was found that the pattern of drug use at Praya Hospital in 2021 was given the highest from each group namely the oral antidiabetic drug group (OAD) was in the Biguanid class with 61 drugs (8,13%), while insulin drugs were in the Rapid-Acting class with 343 drugs (45,73%), and the OAD + Insulin combination with 119 drugs (15,87%). For the HbA1c profile, high HbA1c levels were found in 76 patients (79%). This shows that blood glucose control is not reasonable. Based on the study's results, the recommended recommendation is that patients routinely control blood sugar and be educated on the accuracy of drug use to control blood sugar.

White adipose tissue, a novel antirheumatic target: Clues from its secretory capability and adipectomy-based therapy.

White adipose tissue (WAT) is involved in rheumatoid arthritis (RA). This study explored its potential as an antirheumatic target. WAT status of healthy and adjuvant-induced arthritis (AIA) rats were compared. The contribution of WAT to RA pathology was evaluated by pre-adipocyte transplant experiments and by dissecting perirenal fat pads of AIA rats. The impact of RA on WAT was investigated by culturing pre-adipocytes. Proteins differentially expressed in WAT of healthy and AIA rats were identified by the UPLC/MS2 method. These together with PPARγ siRNA and agonist were used to treat pre-adipocytes in vitro. The medium was used for THP-1 monocyte culture. Compared with healthy controls, AIA WAT was smaller but secreted more leptin, eNAMPT, MCP-1, TNF-α, and IL-6. AIA rat pre-adipocytes increased the levels of these adipokines in healthy recipients. RA patients' serum induced a similar secretion change and impaired differentiation of pre-adipocytes. Adipectomy eased AIA-related immune abnormalities and arthritic manifestations. Hepatokines PON1, IGFBP4, and GPIHBP1 were among the differential proteins in high levels in RA blood, and induced inflammatory secretions by pre-adipocytes. GPIHBP1 inhibited PPARγ expression and caused differentiation impairment and inflammatory secretion by pre-adipocytes, a similar outcome to PPARγ-silencing. This endowed the cells with an ability to activate monocytes, which can be abrogated by rosiglitazone. Certain hepatokines potentiate inflammatory secretions by pre-adipocytes and expedite RA progression by inhibiting PPARγ. Targeting this signalling or abnormal WAT secretion by various approaches may reduce RA severity.

GDF9His209GlnfsTer6/S428T and GDF9Q321X/S428T bi-allelic variants caused female subfertility with defective follicle enlargement

BackgroundAntral follicles consist of an oocyte cumulus complex surrounding by somatic cells, including mural granulosa cells as the inner layer and theca cells as the outsider layer. The communications between oocytes and granulosa cells have been extensively explored in in vitro studies, however, the role of oocyte-derived factor GDF9 on in vivo antral follicle development remains elusive due to lack of an appropriate animal model. Clinically, the phenotype of GDF9 variants needs to be determined.MethodsWhole-exome sequencing (WES) was performed on two unrelated infertile women characterized by an early rise of estradiol level and defect in follicle enlargement. Besides, WES data on 1,039 women undergoing ART treatment were collected. A Gdf9Q308X/S415T mouse model was generated based on the variant found in one of the patients.ResultsTwo probands with bi-allelic GDF9 variants (GDF9His209GlnfsTer6/S428T, GDF9Q321X/S428T) and eight GDF9S428T heterozygotes with normal ovarian response were identified. In vitro experiments confirmed that these variants caused reduction of GDF9 secretion, and/or alleviation in BMP15 binding. Gdf9Q308X/S415T mouse model was constructed, which recapitulated the phenotypes in probands with abnormal estrogen secretion and defected follicle enlargement. Further experiments in mouse model showed an earlier expression of STAR in small antral follicles and decreased proliferative capacity in large antral follicles. In addition, RNA sequencing of granulosa cells revealed the transcriptomic profiles related to defective follicle enlargement in the Gdf9Q308X/S415T group. One of the downregulated genes, P4HA2 (a collagen related gene), was found to be stimulated by GDF9 protein, which partly explained the phenotype of defective follicle enlargement.ConclusionsGDF9 bi-allelic variants contributed to the defect in antral follicle development. Oocyte itself participated in the regulation of follicle development through GDF9 paracrine effect, highlighting the essential role of oocyte-derived factors on ovarian response.

Potential functionality of Cutibacterium acnes extracellular vesicles in atopic dermatitis and acne vulgaris: A comparative proteomic analysis.

Cutibacterium acnes is a commensal bacterium residing in healthy skin and plays a critical role in maintaining skin homeostasis. C. acnes has been considered closely related to acne vulgaris, while recent studies suggest that C. acnes and its metabolites may have a protective role in atopic dermatitis (AD) by modulating the immune system and maintaining skin homeostasis. Extracellular vesicles (EVs) are small membranous vesicles secreted by bacteria that participate in bacteria-host interactions. This study first compared C. acnes EVs from AD lesions (AD-EVs), acne lesions (Acne-EVs), and healthy skin (NC-EVs), using Label-free quantitative LC-MS/MS and validated differently expressed proteins by parallel reaction monitoring (PRM). Then Normal Human Epidermal Keratinocytes (NHEK) and human primary keratinocytes (KC) were treated with C. acnes EVs isolated from different groups, and the expressions of inflammatory factors were measured by quantitative real-time PCR and Western blotting. Compared with the acne group, the AD group showed greater downregulation of proteins related to energy metabolism and carbon source utilization pathway. Differences in protein profile in AD and acne lesion-separated C. acnes EVs correspond to the abnormal sebum secretion pattern in both diseases. C. acnes EVs from different groups affected different expressions of Th1 and Th2 inflammatory factors and epidermal barrier markers in NHEK and KC, indicating different immunomodulatory potentials. This study observed distinct proteomic differences between AD-EVs and Acne-EVs, and provided insights into the functional differences of C. acnes EVs in AD and acne.

Exploration of the core pathway of inflammatory bowel disease complicated with metabolic fatty liver and two-sample Mendelian randomization study of the causal relationships behind the disease.

Inflammatory bowel disease (IBD) is often associated with complex extraintestinal manifestations. The incidence of nonalcoholic fatty liver disease (NAFLD) in IBD populations is increasing yearly. However, the mechanism of interaction between NAFLD and IBD is not clear. Consequently, this study aimed to explore the common genetic characteristics of IBD and NAFLD and identify potential therapeutic targets. Gene chip datasets for IBD and NAFLD were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to identify modules in those datasets related to IBD and NAFLD. ClueGO was used for biological analysis of the shared genes between IBD and NAFLD. Based on the Human MicroRNA Disease Database (HMDD), microRNAs (miRNAs) common to NAFLD and IBD were obtained. Potential target genes for the miRNAs were predicted using the miRTarbase, miRDB, and TargetScan databases. Two-sample Mendelian randomization (MR) and two-way MR were used to explore the causal relationship between Interleukin-17 (IL-17) and the risk of IBD and NAFLD using data from GWAS retrieved from an open database. Through WGCNA, gene modules of interest were identified. GO enrichment analysis using ClueGO suggested that the abnormal secretion of chemokines may be a common pathophysiological feature of IBD and NAFLD, and that the IL-17-related pathway may be a common key pathway for the pathological changes that occur in IBD and NAFLD. The core differentially expressed genes (DEGs) in IBD and NAFLD were identified and included COL1A1, LUM, CCL22, CCL2, THBS2, COL1A2, MMP9, and CXCL8. Another cohort was used for validation. Finally, analysis of the miRNAs identified potential therapeutic targets. The MR results suggested that although there was no causal relationship between IBD and NAFLD, there were causal relationships between IL-17 and IBD and NAFLD. We established a comorbid model to explain the potential mechanism of IBD with NAFLD and identified the chemokine-related pathway mediated by cytokine IL-17 as the core pathway in IBD with NAFLD, in which miRNA also plays a role and thus provides potential therapeutic targets.

Identification of a novel intronic variant of ATP6V0A2 in a Han-Chinese family with cutis laxa.

Cutis laxa is a connective tissue disease caused by abnormal synthesis or secretion of skin elastic fibers, leading to skin flabby and saggy in various body parts. It can be divided into congenital cutis laxa and acquired cutis laxa, and inherited cutis laxa syndromes is more common in clinic. In this study, we reported a case of a Han-Chinese male newborn with ATP6V0A2 gene variant leading to cutis laxa. The proband was identified by whole-exome sequencing to determine the novel variant, and their parents were verified by Sanger sequencing. Bioinformatics analysis and minigene assay were used to verify the effect of this variant on splicing function. The main manifestations of the proband are skin laxity, abnormal facial features, and enlargement of the anterior fontanelle. Whole-exome sequencing showed that the newborn carried a non-canonical splicing-site variant c.117 + 5G > T, p. (?) in ATP6V0A2 gene. Sanger sequencing showed that both parents of the proband carried the heterozygous variant. The results of bioinformatics analysis and minigene assay displayed that the variant site affected the splicing function of pre-mRNA of the ATP6V0A2 gene. In this study, it was identified that ATP6V0A2 gene c. 117 + 5G > T may be the cause of the disease. The non-canonical splicing variants of ATP6V0A2 gene were rarely reported in the past, and this variant expanded the variants spectrum of the gene. The functional study of minigene assay plays a certain role in improving the level of evidence for the pathogenicity of splicing variants, which lays a foundation for prenatal counseling and follow-up gene therapy.

Endocrinopatias com impacto no sistema cardiovascular canino

The synthesis and secretion of hormones is performed by endocrine glands which, when under the effect of physiological disturbance, can result in abnormal hormonal secretion, leading to alterations in the organism's functionality, stimulus, or physiological response. Hormonal secretion at levels below or above necessary can result in cardiovascular changes that may be presented as symptoms commonly confused with behavioral characteristics, racial association, sedentary lifestyle, aging, or even nutritional management failure. Prolonged exposure to lower levels of hormonal secretion can lead the endocrine patient to develop chronic changes in cardiac functionality such as arrhythmia and bradycardia, as well as anatomical changes such as left ventricular hypertrophy and narrowing of the vena cava. Moreover, the dog may present laboratorial alterations and specific symptoms that can act as obstacles for the physiological functioning of the cardiovascular system, such as weight gain, muscle weakness, lethargy, hyperkalemia, hypercortisolemia and hyperglycemia. This paper lists the main impacts of endocrinopathies on the cardiovascular system, aiming to raise awareness among veterinarians of the importance of cardiovascular monitoring, both during and after the end of treatment or stabilization of an endocrinopathy.

EFFECT OF TRIGONA LAEVICEPS HONEY ON DECREASED GLUCOSE LEVELS IN MALE RATS (RATTUS NOVERGICUS)

ABSTRACT
 
 Diabetes mellitus (DM) is a metabolic disease characterized by increased blood sugar levels (hyperglycemia) which occurs due to abnormalities in insulin secretion, insulin action or both. People use many herbal remedies, one of which is Trigona laeviceps honey. This study aims to determine the effect of giving Trigona laeviceps honey on reducing glucose levels in male rats (Rattus novergicus L). This research was an experimental study using 28 Wistar rats (Rattus norvegicus) which were then analyzed by the Kruskall Wallis test to determine differences in glucose levels in the groups. The results showed that there was a decrease in glucose levels in the group given Trigona laeviceps honey and a significant difference in mean glucose levels was obtained based on the treatment group (p 0.000).
 Keywords : Trigona leaviceps honey, DM, blood glucose.

Biophysical Evidence for the Amyloid Formation of a Recombinant Rab2 Isoform of Leishmania donovani.

The most fatal form of Visceral leishmaniasis or kala-azar is caused by the intracellular protozoan parasite Leishmania donovani. The life cycle and the infection pathway of the parasite are regulated by the small GTPase family of Rab proteins. The involvement of Rab proteins in neurodegenerative amyloidosis is implicated in protein misfolding, secretion abnormalities and dysregulation. The inter and intra-cellular shuttlings of Rab proteins are proposed to be aggregation-prone. However, the biophysical unfolding and aggregation of protozoan Rab proteins is limited. Understanding the aggregation mechanisms of Rab protein will determine their physical impact on the disease pathogenesis and individual health. This work investigates the acidic pH-induced unfolding and aggregation of a recombinant Rab2 protein from L. donovani (rLdRab2) using multi-spectroscopic probes. The acidic unfolding of rLdRab2 is characterised by intrinsic fluorescence and ANS assay, while aggregation is determined by Thioflavin-T and 90⁰ light scattering assay. Circular dichroism determined the secondary structure of monomers and aggregates. The aggregate morphology was imaged by transmission electron microscopy. rLdRab2 was modelled to be a Rab2 isoform with loose globular packing. The acidinduced unfolding of the protein is a plausible non-two-state process. At pH 2.0, a partially folded intermediate (PFI) state characterised by ~ 30% structural loss and exposed hydrophobic core was found to accumulate. The PFI state slowly converted into well-developed protofibrils at high protein concentrations demonstrating its amyloidogenic nature. The native state of the protein was also observed to be aggregation-prone at high protein concentrations. However, it formed amorphous aggregation instead of fibrils. To our knowledge, this is the first study to report in vitro amyloid-like behaviour of Rab proteins in L donovani. This study provides a novel opportunity to understand the complete biophysical characteristics of Rab2 protein of the lower eukaryote, L. donovani.

Renal Hypokalemia: An Endocrine Perspective.

The majority of disorders that cause renal potassium wasting present with abnormalities in adrenal hormone secretion. While these findings frequently lead patients to seek endocrine evaluation, clinicians often struggle to accurately diagnose these conditions, delaying treatment and adversely impacting patient care. At the same time, growing insight into the genetic and molecular basis of these disorders continues to improve their diagnosis and management. In this review, we outline a practical integrated approach to the evaluation of renal hypokalemia syndromes that are seen in endocrine practice while highlighting recent advances in understanding of the genetics and pathophysiology behind them.

A Supramolecular Assembly of EGCG for Long-Term Treatment of Allergic Rhinitis.

Allergic rhinitis (AR) is a type-I hypersensitivity disease mediated by immunoglobulin E (IgE). Although antihistamines, glucocorticoids, leukotriene receptor antagonists, and other drugs are widely used to treat AR, the various adverse side effects of long-term use of these drugs should not be ignored. Therefore, more effective and safe natural alternative strategies are urgently needed. To this end, this study designed a nanosupramolecular delivery system composed of β-cyclodextrin supramolecular polymer (PCD), thiolated chitosan (TCS), and natural polyphenol epigallocatechin gallate (EGCG) for intranasal topical continuous treatment of AR. The TCS/PCD@EGCG nanocarriers exhibited an excellent performance in terms of retention and permeability in the nasal mucosa and released the vast majority of EGCG responsively in the nasal microenvironment, thus resulting in the significantly high antibacterial and antioxidant capacities. According to the in vitro model, compared with free EGCG, TCS/PCD@EGCG inhibited mast cell activity and abnormal histamine secretion in a more long-term and sustained manner. According to the in vivo model, whether in the presence of continuous or intermittent administration, TCS/PCD@EGCG substantially inhibited the secretion of allergenic factors and inflammatory factors, mitigated the pathological changes of nasal mucosa, alleviated the symptoms of rhinitis in mice, and produced a satisfactory therapeutic effect on AR. In particular, the therapeutic effect of TCS/PCD@EGCG systems were even superior to that of budesonide during intermittent treatment. Therefore, the TCS/PCD@EGCG nanocarrier is a potential long-lasting antiallergic medicine for the treatment of AR.

Advances in clinical research on glucagon.

We are now celebrating the 100th anniversary of the discovery of an important pancreatic hormone, glucagon. Glucagon is historically described as a diabetogenic hormone elevating glucose levels via increases in insulin resistance and hepatic gluconeogenesis. The more recently identified actions of glucagon include not only its pathophysiologic effects on glucose metabolism but also its significant roles in amino-acid metabolism in the liver. The possibility that abnormalities in α-cells' secretion of glucagon in metabolic disorders are a compensatory adaptation for the maintenance of metabolic homeostasis is another current issue. However, the clinical research concerning glucagon has been considerably behind the advances in basic research due to the lack of suitable methodology for obtaining precise measurements of plasma glucagon levels in humans. The precise physiology of glucagon secretory dynamics in individuals with metabolic dysfunction (including diabetes) has been clarified since the development in 2014 of a quantitative measurement technique for glucagon. In this review, we summarize the advances in the clinical research concerning glucagon, including those of our studies and the relevant literature.

N-Acetylcysteine Alleviates D-Galactose-Induced Injury of Ovarian Granulosa Cells in Female Rabbits by Regulating the PI3K/Akt/mTOR Signaling Pathway.

The ovary plays a crucial role in the reproductive system of female animals. Ovarian problems such as ovarian insufficiency, premature aging, polycystic ovary syndrome, and ovarian cysts may lead to ovulation disorders, abnormal hormone secretion, or luteal dysfunction, thereby increasing the risk of infertility and abortion. Only when the ovarian function and other organs in the reproductive system remain healthy and work normally can female animals be ensured to carry out reproductive activities regularly, improve the pregnancy rate and litter size, promote the healthy development of the fetus, and then improve their economic value. The follicle, as the functional unit of the ovary, is composed of theca cells, granulosa cells (GCs), and oocytes. GCs are the largest cell population and main functional unit in follicles and provide the necessary nutrients for the growth and development of follicles. N-acetylcysteine (NAC) is a prevalent and cell-permeable antioxidant molecule that effectively prevents apoptosis and promotes cellular survival. Over the past few years, its function in boosting reproductive performance in animals at the cellular level has been widely acknowledged. However, its specific role and mechanism in influencing GCs is yet to be fully understood. The objective of this study was to examine the effects of NAC on ovarian damage in female rabbits. For this purpose, D-galactose (D-gal) was first used to establish a model of damaged GCs, with exposure to 1.5 mg/mL of D-gal leading to substantial damage. Subsequently, varying concentrations of NAC were introduced to determine the precise mechanism through which it influences cell damage. Based on the results of the Cell Counting Kit-8 assay, flow cytometry, and Western blotting, it was found that 0.5 mg/mL of NAC could significantly suppress cell apoptosis and promote proliferation. In particular, it decreased the expression levels of Bax, p53, and Caspase-9 genes, while concurrently upregulating the expression of the BCL-2 gene. Moreover, NAC was found to alleviate intracellular oxidative stress, suppress the discharge of mitochondrial Cytochrome c, and boost the enzymatic activities of CAT (Catalase), GSH (Glutathione), and SOD (Superoxide dismutase). RNA sequencing analysis subsequently underscored the critical role of the PI3K/Akt/mTOR pathway in governing proliferation and apoptosis within GCs. These findings demonstrated that NAC could significantly influence gene expression within this pathway, thereby clarifying the exact relationship between the PI3K/Akt/mTOR signaling cascade and the underlying cellular processes controlling proliferation and apoptosis. In conclusion, NAC can reduce the expression of Bax, p53, and Caspase-9 genes, inhibit the apoptosis of GCs, improve cell viability, and resist D-gal-induced oxidative stress by increasing the activity of CAT, GSH, and SOD. The molecular mechanism of NAC in alleviating D-gal-induced ovarian GC injury in female rabbits by regulating the PI3K/Akt/mTOR signaling pathway provides experimental evidence for the effect of NAC on animal reproductive function at the cellular level.

The Impact of Atmospheric Cadmium Exposure on Colon Cancer and the Invasiveness of Intestinal Stents in the Cancerous Colon.

Inhalation exposure to carcinogenic metals such as cadmium (Cd) is a significant global health concern linked to various cancers. However, the precise carcinogenic mechanism underlying inhalation exposure remains elusive. In this study, CT26 mouse colon cancer (CC) cells were implanted into BALB/c mice to establish CC mouse models. Some of the CC mice were implanted with intestinal stents. The mice were exposed to atomized oxygen and nitrogen (O2/N2) gas containing Cd. Atmospheric Cd intensified inflammation in CC cells and heightened Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase 1 (NOX1) activity, which is an indirect measurement of increased reactive oxygen species (ROS) production. This escalated ROS production triggered abnormal Wnt protein secretion, activated the Wnt/β-catenin signaling pathway, and stimulated CC cell proliferation. No discernible body weight effect was seen in the CC mice, possibly due to the later-stage tumor weight gain, which masked the changes in body weight. Cd facilitated colon tumor restructuring and cell migration at the later stage. The implantation of intestinal stents inhibited the expression of Superoxide Dismutase 1 (SOD1) in the colon tumors of the CC mice, with no evident effects on the expression levels of NOX1, SOD2, and Catalase (CAT) enzymes. Elevated ROS levels, indirectly reflected by enzyme activity, did not substantially impact the Wnt/β-catenin signaling pathway and even contributed to slowing its imbalance. Stent implantation eased the inflammation occurring in colon tumors by reducing CC cell proliferation but it induced discomfort in the mice, leading to a reduction in food intake and weight. Cd partially fosters CC tumorigenesis via the ROS-mediated Wnt/β-catenin signaling pathway. The effect of Cd on the invasive effect of intestinal stents in the cancerous colon is not significant.