Assessment of the Effects of Supplemental Rumen Protected B Vitamins and Choline for Periparturient Cows: A Meta-Analysis of 28 Feeding Studies

There are currently no prescribed requirements for B vitamins or choline for dairy cows during the transition period, but many recent studies have shown a variety of benefits from supplying these nutrients to periparturient cows. The purpose of this research effort was to determine the potential benefit of including a rumen protected blend composed of B vitamins (riboflavin, folic acid, vitamin B12) and choline (RPBlend, Jefo Nutrition Inc., St. Hyacinthe, QC, Canada) for dairy cows during the transition period, based on results from 28 on-farm feeding studies (USA-12, Mexico-7, Canada-4, Chile-3, Australia-1, Brazil-1) conducted between 2011 and 2018. All farms participated in monthly herd management record keeping systems and were selected to participate in studies due to their excellent management. Meta-analyses in which risk differences were determined were used to assess the effects of the supplemental RPBlend on health parameters and reproduction. The effect size was used as the determinant of the possible contribution of RPblend on the yields of milk, energy corrected milk (ECM), fat and protein yields during the first four weeks of lactation. Results showed that the inclusion of RPblend reduced (P < 0.05) involuntary culling and mastitis by cows during the first 30 days after calving. There was a tendency (P < 0.10) for reduced retained placenta and metritis. The meta-analyses revealed that the risk of the displaced abomasum and milk fever did not diminish (P > 0.10) with the inclusion of the BPBlend. The incidence rate of subclinical ketosis, determined as blood beta hydroxy butyric acid greater than 1.2 mM was lower (P (than those not supplemented. The proportion of cows confirmed pregnant by 100 days in milk was greater for cows given the BPBlend (P < 0.05). Milk yield and ECM were greater for cows receiving the RPBlend (1.13 and 0.93 kg/cow respectively, P < 0.05). There was no change in fat yield (P > 0.10) while the yield of milk protein was greater (P < 0.05) when the cows received the blend. These results suggest that the inclusion of rumen protected B vitamins and choline can assist cow health, reproduction and production at the start of lactation.

SIMULTANEOUS DETERMINATION OF FAT SOLUBLE VITAMINS A, D_3, E AND K_1 IN FORTIFIED MILK POWDERS BY HPLC

A high performance liquid chromatographic method for the simultaneous determination of four fat soluble vitamins: retinol (vitamin A), cholecalciferol(vitamin D), tocopherol(vitamin E) and phylloquinone(vitamin K_1) in fortified milk powders and egg yolk has been developed. The method requires enzymatic hydrolysis of lipid component of the sample as a pretreatment. Several factors which influence the enzymatic hydrolysis were studied-Separation was achieved using μ-Bondapak C-18 column(3.9×300mm), 98% methanol as mobile phase, a double channel detection was selected; vitamins D_3 E_1 K_1 were detected by UV spectrophotometry (265 nm) first, then vitamin A by fluorometry (EX 325nm, EM 480mm). The retention times of vitamin A_1 D_3, E and K_1 4.87, 9.00, 10.58 and 15.45 min respectively. Detection limit were 0.64, 0.25, 0.50 and 0.07 ng; and the recoveries were 90.5%～103.6% 90.0%～95.6%, 91.7%～98.8%, 91.5%～98.6%, respectively. The vitamins A, D_0, E, K_1 contents in foods were determined satisfactorily.

Protective effect of some vitamins against the toxic action of ethanol on liver regeneration induced by partial hepatectomy in rats

AIM: To investigate the effects of vitamins (A, C and E) on liver injury induced by ethanol administration during liver regeneration in rats. METHODS: Male Wistar rats subjected to 70% partial hepatectomy were divided into five groups (groups 1-5). During the experiment, animals of Group 1 drank only water. The other four groups (2-5) drank 30 mL of ethanol/L of water. Group 3 additionally received vitamin A, those of group 4 vitamin C and those of group 5 received vitamin E. Subsequently serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin and bilirubin were measured colorimetrically. Lipid peroxidation (thiobarbituric-acid reactive substances, TBARS) both in plasma and liver was measured, as well as liver mass gain assessment and total DNA. RESULTS: Compared with sham group, serum AST and ALT increased significantly under ethanol treatment (43% and 93%, respectively, with P < 0.05). Vitamin C and vitamin E treatment attenuated the ethanol-induced increases in ALT and AST activity. Ethanol treatment also decreased serum albumin concentration compared to sham group (3.1 ± 0.4 g/dL vs 4.5 ± 0.2 g/dL; P < 0.05). During liver regeneration vitamins C and E significantly ameliorated liver injury for ethanol administration in hepatic lipid peroxidation (4.92 nmol/mg and 4.25 nmol/mg vs 14.78 nmol/mg, respectively, with P < 0.05). In association with hepatic injury, ethanol administration caused a significant increase in both hepatic and plasma lipid peroxidation. Vitamins (C and E) treatment attenuated hepatic and plasma lipid peroxidation. CONCLUSION: Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus appear to be significantly more effective than vitamin A against ethanol-mediated toxic effects during liver regeneration.

Effects of Dietary Vitamins A,B_2,and B_6 Supplementation on Growth and Feed Utilization of Juvenile Chinese Soft-shelled Turtle Pelodiscus sinensis according to an Orthogonal Array Experiment

An orthogonal experimental design OA9 （33） was used to evaluate the effects of vitamins （A, B2, and B6） on the growth and digestive ability of the juvenile Chinese soft-shelled turtle, Pelodiscus sinensis （initial weight, 5.9-0.2 g）. A total of 135 turtles were divided into 9 groups, which each included 15 individuals. The results revealed that vitamin A （VA） had the strongest impacts on the growth rate and feed utilization among the three vitamins; 35,000 IU kg^-1 VA had optimal effects on the feeding intake and specific growth rate, and 20,000 IU kg^-1 VA had optimal effects on protein digestibility and the feed conversion ratio. Vitamin B2 （VB2） was essential for regulating protein deposition and the energy efficiency for growth of the turtles; 120 mg kg^-1 VB2 resulted in increased protein and energy deposition, and 180 mg kg^-1 VB2 had greater beneficial effects on the growth rate. Vitamin B6 （VB6） had important effects on protein and feed efficiency; however, VB6 at an excessive level （120 mg kg^-1） restricted turtle growth. Based on the above growth results, dietary supplementation ofVA, VB2 and VB6 at levels of 35,000 IU kg^-1, 180 mg kg^-1 and 70 mg kg^-1, respectively, were recommended for the juvenile soft-shelled turtle.

Potential Inhibitory Effect of Vitamins Against COVID-19

Coronavirus disease 2019(COVID-19)is a current pandemic that has affected more than 195 countries worldwide.In this severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic,when treatment strategies are not yet clear and vaccines are not available,vitamins are an excellent choice to protect against this viral infection.The rationale behind this study was to examine the inhibitory effect of vitamins B,C,and D against the main protease of SARSCoV-2 and angiotensin-converting enzyme 2(ACE2),which have critical rolesin the immune system.Molecular docking,performed by using MOE-Dock of the Chemical Computing Group,was used to understand the mechanism.The vitamins all docked within the active sites of the Mpro(PDB ID:6LU7)and ACE2 receptor proteins(PDB ID:6VW1).Vitamins B and C delivered maximum energy scores against both targets,while vitamin D displayed a binding energy score of−7.9532 kcal/mol for M^(pro) and−7.9297 for ACE2.The efficiency of all three vitamins is higher than the binding energy score of chloroquine(−6.889 kcal/mol),which is now under clinical trials.The use of vitamins is beneficial,being immune system restorative,and they also act as anti-COVID agents.Although the potential beneficial effects of vitamin B and C are revealed through docking studies,further clinical trials are required for the validation of these results.

An Association of Vitamins A and E with Hyaluronic and Lactobionic Acids may Prevent Molecular Changes Associated with Keratocyte to Myofibroblast Transition

Inflammatory events in the corneal stroma may activate keratocytes and trigger their transition towards myofibroblasts,which now produce different extracellular matrix(ECM)proteins thus causing corneal opacification.Corneal haze is a frequent side effect after photorefractive keratectomy(PRK)to correct high myopia.Currently,a preventive treatment with mitomycin-c can be used to limit the occurrence of this phenomenon.However,mitomycin-c is a toxic drug,not devoid of side effects,which may occasionally involve the corneal endothelium.Therefore,we have searched for a less risky,natural way,to prevent keratocytes transition.To this purpose,we have used as markers of the phenotype switch the proteins lumican(highly expressed by keratocytes and much less by myofibroblasts)and smooth muscle actin(αSMA)(highly expressed by myofibroblasts and poorly found in keratocytes),beside Fibronectin(Fn),the expression of which is also increased by transforming growth factor-beta(TGFβ)treatment.Treatment of human keratocytes with TGFβwas used to induce the protein shift.Among different possible candidates,we have found that vitamins A and E,hyaluronic and lactobionic acids may prevent,either alone,or much better in association,the shift in the ratio between lumican andαSMA and the increased Fn expression.In conclusion,it could be speculated that topic treatment of the ocular surface with an association of these four compounds could be able to prevent or at least limit the occurrence of post-PRK corneal haze,with the additional advantage of lubrication,hydration and antioxidant defense exerted by these molecules.

Epidemic management in a measles outbreak in 2023,the return of vaccine-preventable diseases:A single center,retrospective observational study

Objective:To investigate the importance of immunization in preventing measles infection and to determine the most useful laboratory tests for confirmation of measles.Methods:This study included pediatric cases evaluated with a presumed diagnosis of measles between December 2022 and June 2023,at Marmara University Pendik Training and Research Hospital.The effects of vaccination status and underlying disease on the clinical course,treatments,and complications were evaluated.Results:In total,117 patients were enrolled in the study with a median age of 80 months(IQR:32.5-125.0).Twelve patients with contact history were asymptomatic and had an underlying disorder,and intravenous immunoglobulin was given to them for post-exposure prophylaxis.Fifty-one patients had confirmed measles diagnosis.Ribavirin treatment was given to three patients(a newborn,a girl with rhabdomyosarcoma,and a healthy boy)with respiratory distress.Seventy-eight percent of confirmed measles cases were unvaccinated,and all hospitalized cases were unvaccinated or under-vaccinated.Four full-vaccinated children had confirmed measles infection.Measles PCR from nasopharyngeal swabs was negative in all of them,and their diagnosis was established with anti-measles IgM positivity.Conclusions:The measles vaccine is the most effective way to protect from measles and measles-related complications.Although measles can also occur in fully vaccinated patients,the disease is milder than in unvaccinated patients.Using ELISA and RT-PCR tests together may be beneficial in patients with high clinical suspicion for early diagnosis.

Vitamin D,selenium,and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis

BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.

Calcium-fortified fresh milk ameliorates postmenopausal osteoporosis via regulation of bone metabolism and gut microbiota in ovariectomized rats

The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy.After 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical testing.The results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid biosynthesis.Furthermore,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and microarchitecture.Mechanistically,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.

Metabolic disorders in prediabetes:From mechanisms to therapeutic management

Diabetes,one of the world's top ten diseases,is known for its high mortality and complication rates and low cure rate.Prediabetes precedes the onset of diabetes,during which effective treatment can reduce diabetes risk.Prediabetes risk factors include high-calorie and high-fat diets,sedentary lifestyles,and stress.Consequences may include considerable damage to vital organs,including the retina,liver,and kidneys.Interventions for treating prediabetes include a healthy lifestyle diet and pharmacological treatments.However,while these options are effective in the short term,they may fail due to the difficulty of long-term implementation.Medications may also be used to treat prediabetes.This review examines prediabetic treatments,particularly metformin,glucagon-like peptide-1 receptor agonists,sodium glucose cotransporter 2 inhibitors,vitamin D,and herbal medicines.Given the remarkable impact of prediabetes on the progression of diabetes mellitus,it is crucial to intervene promptly and effectively to regulate prediabetes.However,the current body of research on prediabetes is limited,and there is considerable confusion surrounding clinically relevant medications.This paper aims to provide a comprehensive summary of the pathogenesis of prediabetes mellitus and its associated therapeutic drugs.The ultimate goal is to facilitate the clinical utilization of medications and achieve efficient and timely control of diabetes mellitus.

Unlocking the potential-vitamin D in prostate cancer prevention

Prostate cancer poses a significant health challenge globally,demanding proactive prevention strategies.This editorial explores the emerging role of vitamin D in prostate cancer prevention.While traditionally associated with bone health,vitamin D is increasingly recognized for its broader impact on immune function,cellular signaling,and cancer prevention.Epidemiological studies suggest an intriguing link between vitamin D deficiency and elevated prostate cancer risk,particularly in regions with limited sunlight exposure.Mechanistically,vitamin D regulates cellular processes,inhibiting unchecked cancer cell growth and bols-tering immune surveillance.Personalized prevention strategies,considering individual factors,are deemed essential for harnessing the full potential of vitamin D.To unlock this potential,the future calls for robust research,public awareness campaigns,dietary improvements,and vigilant medical guidance.Collaborative efforts are poised to pave the way toward a future where vitamin D stands as a sentinel in prostate cancer prevention,ushering in hope and improved health for men worldwide.

Role of vitamin D in COVID-19 and other viral infections

Vitamin D is a steroid hormone that is naturally produced in the body or obtained through dietary sources,primarily under the influence of UVB radiation.This essential nutrient has a vital role in numerous physiological processes,encom-passing immune function,cell growth,differentiation,insulin regulation,and cardiovascular well-being,along with its pivotal role in sustaining the delicate equilibrium of calcium and phosphate concentrations in the body.Moreover,vitamin D reinforces mucosal defense and bolsters the immune system through immunomodulation,making it a critical component of overall health.Numerous studies have unveiled the profound connection between vitamin D and the predisposition to respiratory tract infections,including well-known viruses such as influenza and the novel severe acute respiratory syndrome coronavirus 2.Vita-min D deficiency has been consistently linked to increased severity of coronavirus disease 2019(COVID-19)and a heightened risk of mortality among afflicted individuals.Retrospective observational studies have further substantiated these findings,indicating that levels of vitamin D are linked with both the occurrence and severity of COVID-19 cases.Vitamin D has its influence on viral infections th-rough a multitude of mechanisms,such as promoting the release of antimicrobial peptides and fine-tuning the responses of the immune system.Additionally,vitamin D is intertwined with the intricate network of the renin–angiotensin system,suggesting a potential impact on the development of complications related to COVID-19.While further clinical trials and extensive research are warranted,the existing body of evidence strongly hints at the possible use of vitamin D as a valuable tool in the prophylaxis and management of COVID-19 and other viral infectious diseases.

Impact of increasing one-carbon metabolites on traumatic brain injury outcome using pre-clinical models

Traumatic brain injury is a major cause of death and disability worldwide,affecting over 69 million individuals yearly.One-carbon metabolism has been shown to have beneficial effects after brain damage,such as ischemic stroke.However,whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more investigation.The aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain injury.PubMed,Web of Science,and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury outcomes.The search terms included combinations of the following words:traumatic brain injury,dietary supplementation,one-carbon metabolism,and B-vitamins.The focus of each literature search was basic science data.The year of publication in the literature searches was not limited.Our analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recove ry of animals with traumatic brain injury compared to controls.Howeve r,this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delive ry of vitamin supplementation post-traumatic brain injury.The details of supplementation post-traumatic brain injury need to be further investigated.Overall,we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model systems.Further investigation in a clinical setting should be stro ngly considered in co njunction with current medical treatments for traumatic brain injury-affected individuals.

Iodine Nutrition, Thyroid-stimulating Hormone, and Related Factors of Postpartum Women from three Different Areas in China: A Cross-sectional Survey

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women.Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured.Results The median UIC of total and lactating participants were 142.00µg/L and 139.95µg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels.Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

Association of Serum Folate and Vitamin B_(12) Concentrations with Obesity in Chinese Children and Adolescents

Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents.Methods A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,China.Anthropometric indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were utilized.Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of obesity.Results We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)=0.68;95%confidence interval(CI)=0.59,0.78]and abdominal obesity(OR=0.68;95%CI=0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR=0.31,95%CI=0.19,0.50)or abdominal obesity(OR=0.46,95%CI=0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR=2.06,95%CI=1.09,3.91).Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood obesity.Children and adolescents with high levels of vitamin B12 and folate were less likely to be obese.

Selenium,Type-2 Diabetes,and the Possible Protective Role of Vitamin D

Diabetes is a pervasive and serious global health issue.According to the International Diabetes Federation report,463 million adults worldwide were living with diabetes in 2019,and this number is projected to reach 700 million in 2045^([1]).

Extracorporeal membrane oxygenation as a bridging therapy for patients with thiamine deficiency-induced pulmonary arterial hypertension

Thiamine deficiency is characterized by a deficiency of thiamine(vitamin B1),lactic acidosis,pulmonary arterial hypertension(PAH),right-sided heart failure,and peripheral nerve damage.Thiamine deficiency is easily misdiagnosed and missed during clinical practice and is associated with death in severe cases.[1,2]Here we reported a patient who was admitted to the hospital with severe metabolic acidosis and pulmonary hypertension and finally diagnosed with thiamine deficiency by detecting plasma vitamin B1 levels.Since clinically obvious thiamine deficiency is rare,and cases of thiamine deficiency requiring extracorporeal membrane oxygenation(ECMO)treatment are rarer,we believe that our case will be helpful for emergency clinicians.

Bowel function and inflammation: Is motility the other side of the coin?

Digestion and intestinal absorption allow the body to sustain itself and are the emblematic functions of the bowel.On the flip side,functions also arise from its role as an interface with the environment.Indeed,the gut houses microorganisms,collectively known as the gut microbiota,which interact with the host,and is the site of complex immune activities.Its role in human pathology is complex and scientific evidence is progressively elucidating the functions of the gut,especially regarding the pathogenesis of chronic intestinal diseases and inflammatory conditions affecting various organs and systems.This editorial aims to highlight and relate the factors involved in the pathogenesis of intestinal and systemic inflammation.

Association of plasma vitamin A level with type 2 diabetes mellitus:a community aging population-based cross-sectional study

Recent studies indicated that vitamin A(VA)might be involved in the pathology of type 2 diabetes mellitus(T2DM).This cross-sectional study was conducted to explore the association between circulating VA level and T2DM.A total of 1818 subjects aged 50 years old and above were recruited from the community.Binomial logistic regression and restricted cubic spline(RCS)were applied to analyze the association of plasma VA level with the risk of T2DM.Serum VA and lipid-adjusted VA levels of T2DM patients were significantly higher than that of non-T2DM subjects(P<0.05).The ratios of plasma VA/total cholesterol(TC),VA/high-density lipoprotein cholesterol(HDL-c)and VA/low-density lipoprotein cholesterol(LDL-c)were positively associated with the risk of T2DM in the aging population(P<0.05).Compared with the Q1 level,subjects with Q2 to Q3 levels of plasma VA/triglyceride(TG)have decreased risk of T2DM(odds ratio(OR)Q2=0.68,P_(Q2)=0.021;ORQ3=0.59,P_(Q3)<0.01).Our results indicated that the imbalance of circulating lipids and VA might affect the relationship between VA and T2DM.The middle and aging subjects with higher ratios of plasma VA/TC,VA/HDL-c,and VA/LDL-c displayed increased risk for T2DM,but the moderate ratio of VA/TG might protect against risk of T2DM.

Vitamin A regulates mitochondrial biogenesis and function through p38 MAPK‑PGC‑1α signaling pathway and alters the muscle fiber composition of sheep

Background Vitamin A(VA)and its metabolite,retinoic acid(RA),are of great interest for their wide range of physiological functions.However,the regulatory contribution of VA to mitochondrial and muscle fiber composition in sheep has not been reported.Method Lambs were injected with 0(control)or 7,500 IU VA palmitate into the biceps femoris muscle on d 2 after birth.At the age of 3 and 32 weeks,longissimus dorsi(LD)muscle samples were obtained to explore the effect of VA on myofiber type composition.In vitro,we investigated the effects of RA on myofiber type composition and intrinsic mechanisms.Results The proportion of type I myofiber was greatly increased in VA-treated sheep in LD muscle at harvest.VA greatly promoted mitochondrial biogenesis and function in LD muscle of sheep.Further exploration revealed that VA elevated PGC-1αmRNA and protein contents,and enhanced the level of p38 MAPK phosphorylation in LD muscle of sheep.In addition,the number of type I myofibers with RA treatment was significantly increased,and type IIx myofibers was significantly decreased in primary myoblasts.Consistent with in vivo experiment,RA significantly improved mitochondrial biogenesis and function in primary myoblasts of sheep.We then used si-PGC-1αto inhibit PGC-1αexpression and found that si-PGC-1αsignificantly abrogated RA-induced the formation of type I myofibers,mitochondrial biogenesis,MitoTracker staining intensity,UQCRC1 and ATP5A1 expression,SDH activity,and enhanced the level of type IIx muscle fibers.These data suggested that RA improved mitochondrial biogenesis and function by promoting PGC-1αexpression,and increased type I myofibers.In order to prove that the effect of RA on the level of PGC-1αis caused by p38 MAPK signaling,we inhibited the p38 MAPK signaling using a p38 MAPK inhibitor,which significantly reduced RA-induced PGC-1αand MyHC I levels.Conclusion VA promoted PGC-1αexpression through the p38 MAPK signaling pathway,improved mitochondrial biogenesis,and altered the composition of muscle fiber type.