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Experimental Gerontology Aug 2024Ageing is associated with cognitive decline. This study investigated the individual and combined effects of resistance exercise (RE) and whey protein supplementation... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of resistance exercise and whey protein supplementation on cognitive function in older men: secondary analysis of a randomised, double-blind, placebo-controlled trial.
PURPOSE
Ageing is associated with cognitive decline. This study investigated the individual and combined effects of resistance exercise (RE) and whey protein supplementation (PRO) on cognitive function in older men.
METHODS
In a pooled-groups analysis, 36 older men (age: 67 ± 4 years) were randomised to either RE (2 x/week; n = 18) or no exercise (NE; n = 18), and either PRO (2 × 25 g/d whey protein isolate; n = 18) or control (CON, 2 × 23.75 g maltodextrin/d; n = 18). A sub-analysis was also conducted between RE + CON (n = 9) and RE + PRO (n = 9). At baseline and 12 weeks, participants completed a battery of neuropsychological tests (CANTAB; Cambridge Cognition, UK) and neurobiological, inflammatory, salivary cortisol and insulin sensitivity biomarkers were quantified.
RESULTS
PRO improved executive function z-score (+0.31 ± 0.08) greater than CON (+0.06 ± 0.08, P = 0.03) and there was a trend towards improved global cognitive function (P = 0.053). RE and RE + PRO did not improve any cognitive function domains (p ≥ 0.07). RE decreased tumor necrosis factor-alpha (P = 0.02) and interleukin-6 (P = 0.048) concentrations compared to NE, but changes in biomarkers did not correlate with changes in cognitive domains. Muscle strength (r = 0.34, P = 0.045) and physical function (ρ = 0.35-0.51, P < 0.05) outcomes positively correlated with cognitive function domains at baseline, but only Δskeletal muscle index correlated with Δepisodic memory (r = 0.34, P = 0.046) following the intervention.
CONCLUSION
In older men, PRO improved cognitive function, most notably executive functioning. RE did not improve any cognitive function domains but did decrease biomarkers of systemic inflammation. No synergistic effects were observed.
Topics: Humans; Male; Whey Proteins; Resistance Training; Aged; Double-Blind Method; Cognition; Dietary Supplements; Executive Function; Neuropsychological Tests; Middle Aged; Cognitive Dysfunction; Biomarkers; Hydrocortisone; Insulin Resistance
PubMed: 38844183
DOI: 10.1016/j.exger.2024.112477 -
Clinical and Experimental Hypertension... Dec 2024Fibroblast growth factor 21 (FGF21) has a protective effect against cardiovascular disease. However, the role of FGF21 in hypertension remains elusive.
BACKGROUND
Fibroblast growth factor 21 (FGF21) has a protective effect against cardiovascular disease. However, the role of FGF21 in hypertension remains elusive.
METHODS
Ten-week-old male C57BL/6 mice were randomly divided into normal-salt (NS) group, NS+FGF21 group, deoxycorticosterone acetate-salt (DOCA) group and DOCA+FGF21 group. The mice in NS group underwent uninephrectomy without receiving DOCA and 1% NaCl and the mice in DOCA group were subjected to uninephrectomy and DOCA-salt (DOCA and 1% NaCl) treatment for 6 weeks. At the same time, the mice were infused with vehicle (artificial cerebrospinal fluid, aCSF) or FGF21 (1 mg/kg) into the bilateral paraventricular nucleus (PVN) of mice.
RESULTS
Here, we showed that FGF21 treatment lowered DOCA salt-induced inflammation and oxidative stress in the PVN, which reduced sympathetic nerve activity and hypertension. Mechanistically, FGF21 treatment decreased the expression of HNF4α and inhibited the binding activity of HNF4α to the promoter region of ACE2 in the PVN of DOCA salt-treated mice, which further up-regulated ACE2/Ang (1-7) signals in the PVN. In addition, ACE2 deficiency abolished the protective effect of FGF21 in DOCA salt-treated mice, suggesting that FGF21-mediated antihypertensive effect was dependent on ACE2.
CONCLUSIONS
The results demonstrate that FGF21 protects against salt-sensitive hypertension via regulating HNF4α/ACE2/Ang (1-7) axis in the PVN of DOCA salt-treated mice via multi-organ crosstalk between liver, brain and blood vessels.
Topics: Animals; Paraventricular Hypothalamic Nucleus; Fibroblast Growth Factors; Male; Mice; Hypertension; Mice, Inbred C57BL; Angiotensin-Converting Enzyme 2; Hepatocyte Nuclear Factor 4; Desoxycorticosterone Acetate; Oxidative Stress; Blood Pressure; Sodium Chloride, Dietary
PubMed: 38841901
DOI: 10.1080/10641963.2024.2361671 -
BMC Neurology Jun 2024Myasthenia gravis (MG) is a long-term autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue as its primary clinical features....
BACKGROUND
Myasthenia gravis (MG) is a long-term autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue as its primary clinical features. Vitamin D is crucial for both the autoimmune response and skeletal muscle function.
CASE PRESENTATION
Here, we presented a case report documenting the substantial improvement in symptoms experienced by a patient who underwent subtotal gastrectomy for gastric cancer following high-dose Vitamin D supplementation. The patient developed generalized MG two months after the surgery and did not respond adequately to pyridostigmine therapy, experiencing a progressive deterioration of the condition. A significant reduction in vitamin D concentration was observed following subtotal gastrectomy. In response, high-dose vitamin D supplementation was administered to the patient. Within one week of treatment, swallowing symptoms improved, enabling the consumption of a small amount of liquid food. By the second week, substantial swallowing and neck function improvements were evident. After one month, the patient regained the ability to straighten the neck while walking and consumed a regular diet despite persistent difficulties chewing hard food.
CONCLUSIONS
This case underscores the therapeutic potential of vitamin D in alleviating MG symptoms, particularly in individuals with compromised vitamin D levels following gastrectomy. The observed improvements present a new perspective on the possible involvement of vitamin D supplementation in the management of postoperative MG cases.
Topics: Humans; Gastrectomy; Myasthenia Gravis; Vitamin D; Stomach Neoplasms; Male; Female; Aged; Middle Aged; Dietary Supplements
PubMed: 38840065
DOI: 10.1186/s12883-024-03687-z -
Biomedicine & Pharmacotherapy =... Jul 2024The incidence of breast cancer is increasing annually, making it a major health threat for women. Chemoprevention using natural, dietary, or synthetic products has...
The incidence of breast cancer is increasing annually, making it a major health threat for women. Chemoprevention using natural, dietary, or synthetic products has emerged as a promising approach to address this growing burden. Atractylenolide-III (AT-III), a sesquiterpenoid present in various medicinal herbs, has demonstrated potential therapeutic effects against several diseases, including tumors, nonalcoholic fatty liver disease, and cerebral ischemic injury. However, its impact on breast cancer chemoprevention remains unexplored. In this study, we used an N-methyl-N-nitrosourea (NMU)-induced rat breast cancer model and 17β-estradiol (E2)-treated MCF-10A cells to evaluate the chemopreventive potential of AT-III on mammary tumorigenesis. AT-III inhibited mammary tumor progression, evidenced by reduced tumor volume and multiplicity, prolonged tumor latency, and the reversal of NMU-induced weight loss. Furthermore, AT-III suppressed NMU-induced inflammation and oxidative stress through the Nrf2/ARE pathway in breast cancer tissues. In vitro, AT-III effectively suppressed E2-induced anchorage-independent growth and cell migration in MCF-10A cells. Nrf2 knockdown attenuated the protective effects of AT-III, highlighting the pivotal role of Nrf2 in AT-III-mediated suppression of tumorigenesis. The mechanism involves the induction of Nrf2 expression by AT-III through the autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Overall, the results of this study indicate that AT-III is a promising candidate for breast cancer chemoprevention and provide valuable insights into its molecular interactions and signaling pathways.
Topics: Animals; NF-E2-Related Factor 2; Sesquiterpenes; Female; Kelch-Like ECH-Associated Protein 1; Lactones; Autophagy; Signal Transduction; Rats; Humans; Cell Line, Tumor; Rats, Sprague-Dawley; Mammary Neoplasms, Experimental; Oxidative Stress; Methylnitrosourea; Carcinogenesis; Anticarcinogenic Agents; Estradiol
PubMed: 38834007
DOI: 10.1016/j.biopha.2024.116852 -
Cell Death & Disease Jun 2024Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in...
Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo Apoe and Apoo Ldlr mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management. Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.
Topics: Animals; Receptors, LDL; Cholesterol; NF-E2-Related Factor 2; Mice; Mice, Knockout; Mice, Inbred C57BL; Lipid Metabolism; Male; Atherosclerosis; Apolipoproteins; Humans; Liver; Apolipoproteins E; Hyperlipidemias
PubMed: 38830896
DOI: 10.1038/s41419-024-06778-4 -
Journal of Animal Science Jan 2024Angus-cross steers (n = 144; 362 kg ± 20.4) were used to determine the effect of Zn and steroidal implants on performance, trace mineral status, circulating...
Influence of steroidal implants and zinc sulfate supplementation on growth performance, trace mineral status, circulating metabolites, and transcriptional changes in skeletal muscle of feedlot steers.
Angus-cross steers (n = 144; 362 kg ± 20.4) were used to determine the effect of Zn and steroidal implants on performance, trace mineral status, circulating metabolites, and transcriptional changes occurring in skeletal muscle. Steers (n = 6 per pen) were stratified by body weight (BW) in a 3 × 2 factorial. GrowSafe bunks recorded individual feed intake (steer as experimental unit; n = 24 per treatment). Dietary treatments (ZINC; eight pens per treatment) included supplemental Zn as ZnSO4 at 1) 0 (analyzed 54 mg Zn/kg DM; Zn0); 2) 30 mg/kg DM (Zn30); 3) 100 mg Zn/kg DM (Zn100). After 60 d of Zn treatment, steers received a steroidal implant treatment (IMP) on day 0: 1) no implant; NO; or 2) high-potency combination implant (TE-200, Elanco, Greenfield, IN; 200 mg TBA, 20 mg E2; TE200). BWs were taken at days -60, 0, and in 28 d increments thereafter. Liver biopsies for TM analysis and blood for TM, serum glucose, insulin, nonesterified fatty acids (NEFA), urea-N, and IGF-1 analysis were collected on days 0, 20, 40, and 84. Glucose, NEFA, and insulin were used to calculate the revised quantitative insulin sensitivity check index (RQUICKI). Linear and quadratic effects of ZINC were evaluated in SAS 9.4. Means for IMP were separated using the LSMEANS statement with the PDIFF option. Day -60 BW was a covariate for performance and carcass data. Growth performance, plasma, liver, and metabolite data were analyzed as repeated measures. TE200 tended to decrease plasma Zn by 8.4% from days 0 to 20 while NO decreased by 3.6% (IMP × day; P = 0.08). A tendency for a ZINC × day effect on G:F was noted (P = 0.06) driven by Zn30 and Zn100 decreasing significantly from period 0-28 to period 28-56 while Zn0 was similar in both periods. An IMP × day effect was noted for RQUICKI where (P = 0.02) TE200 was greater on day 40 compared to NO cattle, but by day 84 RQUICKI was not different between TE200 and NO. On day 20, increasing Zn supplementation linearly increased mRNA abundance (P ≤ 0.09) of protein kinase B (AKT1), mammalian target of rapamycin (mTOR), matrix metalloproteinase 2 (MMP2), and myogenic factor 5 (MYF5). In this study, Zn and implants differentially affected genes related to energy metabolism, satellite cell function, and TM homeostasis on days 20 and 84 postimplant. These results suggest steroidal implants increase demand for Zn immediately following implant administration to support growth and may influence insulin sensitivity in finishing cattle.
Topics: Animals; Cattle; Male; Muscle, Skeletal; Dietary Supplements; Trace Elements; Zinc Sulfate; Drug Implants; Diet; Animal Feed; Trenbolone Acetate
PubMed: 38828800
DOI: 10.1093/jas/skae154 -
Cureus May 2024Perioperative neurocognitive disorders (PNDs) affect a large percentage of people who undergo surgeries that need general anesthesia. There is an increased risk of... (Review)
Review
Perioperative neurocognitive disorders (PNDs) affect a large percentage of people who undergo surgeries that need general anesthesia. There is an increased risk of death and a major disruption to postoperative self-care as a result of this. This study compiles all the relevant materials that the authors have found to investigate postnatal depression and its causes, as well as the methods used to determine the probability and severity of PNDs and how to reduce their risk before surgery. Postnatal depression can have many causes, and this text explores some of them. These include a history of alcohol or opiate use, immunological dysregulation, advanced age, educational background, infections, neurocognitive impairment, and pre-existing chronic inflammatory disorders. It also delves into various methods used to gauge the likelihood and severity of postpartum depression. The following assessment tools were covered: the Clock Drawing Test, Domain-Specific Tests, the Mini-Mental State Examination, and the Montreal Cognitive Assessment. In addition to biochemical markers, neuroimaging techniques play an important role in diagnosis. The Frailty Fried assessment, which measures inertia, sluggishness, lack of physical activity, fatigue, and unintentional weight loss, is a key prognostic sign that is highlighted. There is strong evidence that the index, which is derived from these five characteristics, may accurately predict the likelihood of PNDs. Risk mitigation strategies are also covered in this research. Preoperative brain plasticity-based therapies, such as physical exercise and intensive cognitive training, can significantly reduce the incidence and severity of postoperative neurocognitive disorders. A peripheral nerve block, monitoring cerebral oxygen saturation, dexmedetomidine, and a reduction in anesthesia depth are all ways to improve anesthetic procedures. Methods that lower blood pressure should be avoided, the body temperature should be kept down during surgery, or the time without liquids should be lengthened; all of these raise the risk of postoperative nausea and vomiting and make it worse. Potential approaches include a Mediterranean diet, physical activity, cognitive stimulation, smoking cessation, alcohol reduction, avoidance of anticholinergic medications, and non-steroidal anti-inflammatory drug stewardship, although there is no definitive evidence for successful postoperative neurocognitive rehabilitation procedures. More standardized diagnostic criteria, evaluation methods, and PND classification are urgently needed, according to this study. Different cases of PNDs are characterized by different combinations of tests, cutoff values, and methods because there is a broad variety of diagnostic tests used to make the diagnosis. Until now, PNDs and pre-existing neurocognitive disorders have been diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). With an aging population comes an increase in the occurrence and prevalence of PNDs, which calls for a specific way to classify and describe the condition.
PubMed: 38826940
DOI: 10.7759/cureus.59436 -
Case Reports in Hepatology 2024Drug-induced liver injury resulting from herbal and dietary supplement use is increasingly common and underrecognized. We report a case of a 34-year-old male...
Drug-induced liver injury resulting from herbal and dietary supplement use is increasingly common and underrecognized. We report a case of a 34-year-old male recreational bodybuilder who presented with muscle cramping, fatigue, and diffuse itching in the setting of bodybuilding supplement use. Labs showed cholestatic liver injury, and liver biopsy revealed bland cholestasis and sinusoidal dilation. He was diagnosed with anabolic-androgenic steroid-induced liver injury. He was symptomatically managed with plasmapheresis for debilitating pruritus. This case highlights drug-induced liver injury as a complication of bodybuilding supplement use containing unlabeled anabolic-androgenic steroids. Sports medicine providers should inquire on herbal and dietary supplement use and be aware of potential contaminants.
PubMed: 38826497
DOI: 10.1155/2024/5112461 -
Biological & Pharmaceutical Bulletin 2024Analysis of endogenous metabolites in various diseases is useful for searching diagnostic biomarkers and elucidating the molecular mechanisms of pathophysiology. The... (Review)
Review
Analysis of endogenous metabolites in various diseases is useful for searching diagnostic biomarkers and elucidating the molecular mechanisms of pathophysiology. The author and collaborators have developed some LC/tandem mass spectrometry (LC/MS/MS) methods for metabolites and applied them to disease-related samples. First, we identified urinary conjugated cholesterol metabolites and serum N-palmitoyl-O-phosphocholine serine as useful biomarkers for Niemann-Pick disease type C (NPC). For the purpose of intraoperative diagnosis of glioma patients, we developed the LC/MS/MS analysis methods for 2-hydroxyglutaric acid or cystine and found that they could be good differential biomarkers. For renal cell carcinoma, we searched for various biomarkers for early diagnosis, malignancy evaluation and recurrence prediction by global metabolome analysis and targeted LC/MS/MS analysis. In pathological analysis, we developed a simultaneous LC/MS/MS analysis method for 13 steroid hormones and applied it to NPC cells, we found 6 types of reductions in NPC model cells. For non-alcoholic steatohepatitis (NASH), model mice were prepared with special diet and plasma bile acids were measured, and as a result, hydrophilic bile acids were significantly increased. In addition, we developed an LC/MS/MS method for 17 sterols and analyzed liver cholesterol metabolites and found a decrease in phytosterols and cholesterol synthetic markers and an increase in non-enzymatic oxidative sterols in the pre-onset stage of NASH. We will continue to challenge themselves to add value to clinical practice based on cutting-edge analytical chemistry methodology.
Topics: Chromatography, Liquid; Animals; Humans; Biomarkers; Tandem Mass Spectrometry; Non-alcoholic Fatty Liver Disease; Carcinoma, Renal Cell; Niemann-Pick Disease, Type C; Glioma; Mice
PubMed: 38825462
DOI: 10.1248/bpb.b24-00073 -
Journal of Animal Science and... Jun 2024The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these...
BACKGROUND
The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these animals are relatively scarce, particularly regarding dietary interventions. Therefore, our study undertook a comprehensive analysis, incorporating both metabolomics and transcriptomics, to explore the effects of a grain-based diet on the functionality of the hypothalamus, as well as on blood and milk in dairy cows.
RESULTS
The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E (PGE) level as a prominent response to the grain-based diet introduction. Furthermore, the hypothalamic transcriptome profiling showed a notable upregulation in amino acid metabolism due to the grain-based diet. Conversely, the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE, including phospholipase A2 (PLA2G4E, PLA2G2A, and PLA2G12B), cyclooxygenase-2 (COX2), and prostaglandin E synthase (PTGES). Additionally, the plasma metabolome analysis indicated a substantial decrease in the level of PGE, along with a decline in adrenal steroid hormones (tetrahydrocortisol and pregnenolone) following the grain-based diet introduction. Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE level. Importantly, PGE was identified as a critical metabolic marker in the hypothalamus, blood, and milk in response to grain intervention. Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus, blood, and milk following the grain-based diet.
CONCLUSIONS
Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet.
PubMed: 38822422
DOI: 10.1186/s40104-024-01034-3