2.Research progress on mTOR signaling pathway and regulatory T cell nutrition metabolic regulation mechanism.
Chinese Journal of Cellular and Molecular Immunology 2024;40(1):69-73
In the tumor microenvironment, metabolic reprogramming can impact metabolic characteristics of T cells, thus inducing immunosuppression to promote tumor immune escape. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in regulating diverse functions of various immune cells. This review mainly focuses on the molecular mechanism of mTOR signaling in regulating cellular energy metabolism process, and the activation status of mTOR signaling under different nutritional environments. In addition, it also summarizes the role of the mTOR signaling in regulatory T cell (Tregs) metabolism and function in current studies, and evaluates the potential of mTOR as a clinical immunotherapeutic target and its current application challenges.
Immunosuppression Therapy
;
Metabolic Reprogramming
;
Signal Transduction
;
Sirolimus
;
T-Lymphocytes, Regulatory
;
TOR Serine-Threonine Kinases
;
Humans
3.Progress in targeted inhibition of aerobic glycolysis combined with immunotherapy for renal cell carcinoma.
Kun ZHANG ; Mengyao RU ; Jiayuan WANG ; Jumei ZHAO ; Lan SHEN
Chinese Journal of Cellular and Molecular Immunology 2024;40(1):74-79
Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.
Humans
;
Carcinoma, Renal Cell/therapy*
;
Immunotherapy
;
Glycolysis
;
Metabolic Reprogramming
;
Kidney Neoplasms/therapy*
;
Tumor Microenvironment
4.Seasonal variations of the prevalence of metabolic syndrome and its markers using big-data of health check-ups.
Hiroe SETO ; Hiroshi TOKI ; Shuji KITORA ; Asuka OYAMA ; Ryohei YAMAMOTO
Environmental Health and Preventive Medicine 2024;29():2-2
BACKGROUND:
It is crucial to understand the seasonal variation of Metabolic Syndrome (MetS) for the detection and management of MetS. Previous studies have demonstrated the seasonal variations in MetS prevalence and its markers, but their methods are not robust. To clarify the concrete seasonal variations in the MetS prevalence and its markers, we utilized a powerful method called Seasonal Trend Decomposition Procedure based on LOESS (STL) and a big dataset of health checkups.
METHODS:
A total of 1,819,214 records of health checkups (759,839 records for men and 1,059,375 records for women) between April 2012 and December 2017 were included in this study. We examined the seasonal variations in the MetS prevalence and its markers using 5 years and 9 months health checkup data and STL analysis. MetS markers consisted of waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG).
RESULTS:
We found that the MetS prevalence was high in winter and somewhat high in August. Among men, MetS prevalence was 2.64 ± 0.42 (mean ± SD) % higher in the highest month (January) than in the lowest month (June). Among women, MetS prevalence was 0.53 ± 0.24% higher in the highest month (January) than in the lowest month (June). Additionally, SBP, DBP, and HDL-C exhibited simple variations, being higher in winter and lower in summer, while WC, TG, and FPG displayed more complex variations.
CONCLUSIONS
This finding, complex seasonal variations of MetS prevalence, WC, TG, and FPG, could not be derived from previous studies using just the mean values in spring, summer, autumn and winter or the cosinor analysis. More attention should be paid to factors affecting seasonal variations of central obesity, dyslipidemia and insulin resistance.
Male
;
Female
;
Humans
;
Metabolic Syndrome/epidemiology*
;
Seasons
;
Prevalence
;
Climate
;
Insulin Resistance
;
Triglycerides
5.Research progress on hereditary endocrine and metabolic diseases associated with sensorineural hearing loss.
Fang CHEN ; Qinying ZHANG ; Qiujing ZHANG ; Qiuju WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2024;38(1):63-69
Hereditary endocrine and metabolic diseases , caused by genetic factors, exhibit complex and diverse symptoms, including the possibility of concurrent sensorineural deafness. Currently, there is a limited clinical understanding of hereditary endocrine and metabolic diseases that manifest with deafness, the pathogenesis remains unclear,and there is a lack of effective diagnostic and treatment methods. This article summarizes the research progress of hereditary endocrine and metabolic diseases complicated with deafness from the pathogenesis, clinical phenotype, diagnosis and treatment. Understanding the current research progress and integrating genetic analysis into clinical practice are crucial for accurate diagnosis and treatment, evaluating clinical efficacy, and providing effective genetic counseling for these diseases.
Humans
;
Deafness/genetics*
;
Hearing Loss, Sensorineural/diagnosis*
;
Phenotype
;
Metabolic Diseases/genetics*
;
Genetic Counseling
6.Age and sex-related Chromogranin A Gene Polymorphisms and its association with metabolic syndrome components
Abdoljalal Marjani ; Nahid Poursharifi ; Atefe Sajedi ; Mahin Tatari
Journal of the ASEAN Federation of Endocrine Societies 2024;39(1):45-52
Introduction:
The purpose of this study was to determine the possible differences in genetic polymorphisms and serum levels of chromogranin A (CgA), according to age and sex, in subjects with and without metabolic syndrome (MetS).
Methodology:
The genotyping and serum level of CgA and biochemical parameters were measured by the T-ARMS-PCR and PCR-RFLP and ELISA and spectrophotometer methods, respectively.
Results:
A comparison of males with and without MetS showed significantly lower high-density lipoprotein-cholesterol (HDL-C) levels than those of females. At ages 30-70 years, both sexes showed significant differences in triglycerides (TG), fasting blood sugar (FBS), CgA levels and waist circumference (WC) when compared to the two groups. Both sexes with MetS indicated significant differences in systolic blood pressure (SBP) at ages 40-70 years, while at ages 40-59 years, there was a significant difference in HDL-C level in males. There was a significant correlation between serum levels of FBS, TG, SBP and WC (in both sexes), and CgA in subjects with MetS. Significant correlation was found between HDL-C level and diastolic blood pressure (DBP), and CgA level in males and females, respectively. CgA genotype frequency (T-415C and C+87T polymorphisms) showed no significant differences between males and females with and without MetS, while there was only a significant difference in frequency of the genotypes T-415C when compared to males with and without MetS.
Conclusion
The CgA appears to be strongly associated with MetS components in both sexes. Variation in CgA gene expression may affect the T–415C polymorphism in males. This may mean that the structure of CgA genetics differs in different ethnic groups. Differences in the serum level and expression of CgA gene may show valuable study results that it may be expected a relationship between these variables and the MetS.
Sex
;
Chromogranin A
;
Genotype
;
Metabolic Syndrome
7.Characteristics and prevalence of Metabolic Syndrome among adult Filipinos with hypothyroidism: A cross-sectional study
Harold Henrison Chiu ; Emilio Villanueva III ; Ramon Larrazabal Jr. ; Anna Elvira Arcellana ; Cecilia Jimeno
Journal of the ASEAN Federation of Endocrine Societies 2024;39(1):53-60
Objectives:
We determined the clinical characteristics and prevalence of metabolic syndrome among adult Filipinos with overt hypothyroidism.
Methodology:
This is a cross-sectional study of 151 adults. Patients were recruited by sequential enrollment. Anthropometric and blood pressure measurements were performed followed by blood extraction for metabolic parameters and thyroid function tests. Clinical and laboratory characteristics were compared between patients with and without metabolic syndrome.
Results:
The prevalence of metabolic syndrome is 40.4% (95%CI: 32.5%, 48.7%). Patients with metabolic syndrome have a waist circumference of 88.4 ± 7.7 cm in females and 93.3 ± 9.0 cm in males. The median fasting blood glucose was 111.4 (52.2) mg/dL, median systolic blood pressure of 120 (30) mm Hg and diastolic blood pressure of 80 (20) mmHg, median serum triglycerides of 174.3 (114.2) mg/dL, median HDL-C of 42.3 (19.2) mg/dL and a proportion of patients with diabetes (23.0%) and hypertension (44.3%), respectively. The presence of increased waist circumference is the most prevalent component seen among hypothyroid patients. There were no differences in terms of age, sex, etiology of hypothyroidism and anti-TPO levels in those with and without metabolic syndrome.
Conclusion
The prevalence of metabolic syndrome in adult Filipinos with hypothyroidism is high. Emphasis must be placed on early screening using waist circumference and metabolic parameters among hypothyroid patients who are at high risk of developing metabolic syndrome.
Dyslipidemias
;
Hypothyroidism
;
Metabolic Syndrome
;
Prevalence
8.The prevalence of metabolic syndrome among adult Filipinos with hypothyroidism: A retrospective cohort study
Harold Henrison C. Chiu, RCh, MD ; Ramon B. Larrazabal Jr., MD ; Anna Elvira S. Arcellana, MD ; Cecilia A. Jimeno, MD, MSc
Acta Medica Philippina 2023;57(7):31-37
Background and Objective:
Dyslipidemia in hypothyroidism results from the effects of thyroid hormones on lipid metabolism. These, in combination with hypothyroidism-induced hemodynamic changes, are risk factors for cardiometabolic diseases. We determined the prevalence of metabolic syndrome (MS) among adult Filipinos with hypothyroidism and compared clinical and laboratory characteristics of those with versus without MS.
Methods:
This is a retrospective study of 105 patients with biochemically confirmed hypothyroidism. A review of
records obtained anthropometric measurements, blood pressure, fasting blood glucose, lipid profile, and thyroid hormones. Clinical and laboratory characteristics were then compared between MS and those without. Significant differences were determined by two-way ANOVA, while heterogeneity of categorical variables was determined by chi-square or Fisher exact test. All data analyses were performed using Stata version 17.0 with a significance level of p<0.05.
Results:
The prevalence of MS is 36.19% (95%CI: 27.04%,46.15%). Body mass index (BMI) peaks at obese class I among those with MS. There is a significantly higher proportion of patients diagnosed to have diabetes (28.95% vs. 7.46%; p=0.003) and hypertension (52.63% vs. 14.93%; p<0.001) in the MS group. No significant differences were noted between groups regarding age, sex, etiology of hypothyroidism, blood pressure, fasting glucose, lipid profile, and thyroid hormone levels.
Conclusion
Our study showed that the prevalence of MS in adult Filipinos with hypothyroidism is increased at
36.19%. Only BMI, presence of diabetes, and hypertension were shown to be significantly higher. Emphasis must be placed on early screening among hypothyroid patients at high risk of developing MS. A prospective study using waist circumference and clinical and metabolic parameters is needed to validate these findings.
dyslipidemia
;
hypothyroidism
;
metabolic syndrome
;
prevalence
9.A case report on SMART-EST action plan with lifestyle medicine approach in the non-pharmacologic management of the metabolic syndrome
Andres Kim L. Tan III, MD, DFM
The Filipino Family Physician 2023;61(1):36-40
Obesity and overweight are considered health risks for non-communicable diseases. Most clinical practice guidelines suggest lifestyle modification as the primary management and as an adjunct to pharmacologic treatment. Using the SMART-EST goaloriented action plan and lifestyle medicine may improve weight reduction outcomes.
The case presented had clinical criteria (3/5) for metabolic syndrome, diagnosed previously as obese stage II, asthma moderately uncontrolled, prediabetes, and mild dyslipidemia. Baseline weight and waist-to-hip ratio were taken and interpreted as obese stage II with a very severe risk for comorbidity.
The diagnostics used were fasting plasma glucose, lipid profile, HbA1c, and 2-D echocardiography on the eight months of intervention only.
Using the SMART-EST action plan plus Lifestyle medicine approaches as non-pharmacologic management for metabolic syndrome. There was an 11.4 % reduction in weight, improved fasting glucose, lipid profile, and 2-D echocardiography within the eight months of intervention.
Metabolic syndrome
10.Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway.
Hongqi ZHANG ; Gang XIANG ; Jiong LI ; Sihan HE ; Yunjia WANG ; Ang DENG ; Yuxiang WANG ; Chaofeng GUO
Chinese Medical Journal 2023;136(12):1468-1477
BACKGROUND:
Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23.
METHODS:
We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined.
RESULTS:
DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown.
CONCLUSIONS
Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.
Humans
;
Osteopontin/genetics*
;
Alkaline Phosphatase/metabolism*
;
Receptor, Fibroblast Growth Factor, Type 3/metabolism*
;
Scoliosis/genetics*
;
Osteoblasts/metabolism*
;
Calcinosis
;
RNA, Messenger/metabolism*
;
Bone Diseases, Metabolic/metabolism*
;
Fibroblast Growth Factors/genetics*


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