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Advances in Genetics 2024Modern humans evolved in Africa some 200,000 years ago, and since then, human populations have expanded and diversified to occupy a broad range of habitats and use... (Review)
Review
Modern humans evolved in Africa some 200,000 years ago, and since then, human populations have expanded and diversified to occupy a broad range of habitats and use different subsistence modes. This has resulted in different adaptations, such as differential responses to diseases and different abilities to digest or tolerate certain foods. The shift from a subsistence strategy based on hunting and gathering during the Palaeolithic to a lifestyle based on the consumption of domesticated animals and plants in the Neolithic can be considered one of the most important dietary transitions of Homo sapiens. In this text, we review four examples of gene-culture coevolution: (i) the persistence of the enzyme lactase after weaning, which allows the digestion of milk in adulthood, related to the emergence of dairy farming during the Neolithic; (ii) the population differences in alcohol susceptibility, in particular the ethanol intolerance of Asian populations due to the increased accumulation of the toxic acetaldehyde, related to the spread of rice domestication; (iii) the maintenance of gluten intolerance (celiac disease) with the subsequent reduced fitness of its sufferers, related to the emergence of agriculture and (iv) the considerable variation in the biosynthetic pathway of long-chain polyunsaturated fatty acids in native populations with extreme diets.
Topics: Humans; Diet; Biological Evolution; Animals; Cultural Evolution; Adaptation, Physiological; Lactase
PubMed: 38908898
DOI: 10.1016/bs.adgen.2024.01.004 -
Experimental and Clinical... Jun 2024Previous work examining the extent to which individuals seek alcohol to enhance positive experiences (reward drinking) or relieve aversive states (relief drinking) has...
Previous work examining the extent to which individuals seek alcohol to enhance positive experiences (reward drinking) or relieve aversive states (relief drinking) has shown that reward/relief drinking predicts response to naltrexone and acamprosate treatment for alcohol use disorder. Yet, various measures of reward/relief drinking have been used in prior research, and the comparative psychometric properties of these measures are unknown. Evaluating and comparing the psychometric properties of these reward/relief drinking measures could identify measures with the most promise for translating precision medicine findings to clinical practice. In a community sample of 65 individuals with heavy/hazardous alcohol use on the Alcohol Use Disorder Identification Test, we showed good internal consistency reliability, test-retest reliability, and concurrent validity for theoretically aligned measures (e.g., reward drinking and reward responsiveness, relief drinking and depression/anxiety symptoms) of the reward and relief subscales across the six measures. We then used ecological momentary assessment to determine whether reward and relief drinking subscales predicted within-person associations between contextual factors of interest (e.g., negative affect, positive affect, distress intolerance, physical pain, hangover symptoms, social drinking situations, alcohol cues) and same-moment alcohol craving. All six measures demonstrated limited predictive validity for alcohol craving contexts in daily life as assessed via ecological momentary assessment. Despite these findings, reward and relief drinking measures show good reliability and concurrent validity and previously demonstrated clinical utility for predicting response to alcohol use disorder treatments, including naltrexone. Future research should aim to elucidate the mechanisms underlying the association between responses to reward/relief drinking measures and pharmacotherapy outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PubMed: 38900509
DOI: 10.1037/pha0000716 -
Zhonghua Jie He He Hu Xi Za Zhi =... Jun 2024Obstructive sleep apnea (OSA) shows sex differences in the pathophysiology, epidemiology, and clinical presentation. Women have different characteristics of OSA at...
Obstructive sleep apnea (OSA) shows sex differences in the pathophysiology, epidemiology, and clinical presentation. Women have different characteristics of OSA at different life stages. Based on 26 guidelines and consensus, 121 English literatures, and 24 Chinese literatures, the Sleep Disorder Group of Chinese Thoracic Society has drafted a consensus with multidisciplinary experts to summarize the epidemiology, clinical characteristics, diagnosis, treatment, and follow-up of OSA in women at different life stages, particularly issues related to OSA during pregnancy. The consensus is divided into four parts: epidemiology, diagnosis, treatment, and issues for pregnant women with OSA, with 34 recommendations covering 13 clinical issues. The aim was to improve the understanding and managements of OSA in women. What is the prevalence of OSA in women at different life stages?The prevalence of OSA varies among women at different life stages. Sex differences are not significant in childhood and adolescence. The prevalence of OSA in women of childbearing age is significantly lower than that in men. The prevalence of OSA increases during pregnancy due to changes in hormone levels and the influence of pregnancy physiology, as well as with gestational weeks. In postmenopausal women, the prevalence of OSA increases significantly, and the sex differences are no longer significant. What are the risk factors for OSA in women at different life stages?The risk factors for OSA in women at different life stages are not identical. (1) Childhood and adolescence: Tonsillar and adenoid hypertrophy, obesity, and craniofacial structural anomalies increase the risk of OSA; (2) Childbearing age: The prevalence of OSA in women is lower than in men. However, obesity, hypothyroidism, acromegaly, and polycystic ovary syndrome increase the risk of OSA, and these patients should be screened for OSA; (3) Pregnancy: hormonal effects, uterine enlargement, and weight changes increase the risk of OSA, especially in those with a history of snoring or OSA before pregnancy; (4) Perimenopausal and post-menopausal periods: Decreased levels of estrogen/progesterone reduce the protective effects on the upper airways, and increase the risk of OSA. Menopause is an important risk factor for OSA in women. What are the harms of OSA in women?OSA is an independent risk factor for diseases such as hypertension, cardiovascular and cerebrovascular diseases, metabolic disorders, emotional and cognitive impairments, and malignant tumors in women. OSA during pregnancy has several adverse effects on maternal and infant health, and is associated with increased risks of preeclampsia, hypertensive disorders complicating pregnancy (HDP), gestational diabetes mellitus (HDM), premature birth, neonatal asphyxia, fetal growth restriction, . What are the clinical symptoms and physical signs of OSA in women?The symptoms of OSA in women are different from those in men. Attention should be paid to whether women snore and the frequency of snoring, especially among postmenopausal and obese women. The atypical symptoms of OSA, including insomnia, daytime fatigue, morning headache, anxiety and nightmares, should not be ignored, especially in postmenopausal, obese, and pregnant women. When should women be screened for OSA?(1) Postmenopausal and pregnant women, as well as women with a first-degree relative with OSA. It should be noted that the clinical symptoms of OSA in women are not typical; (2) Women with polycystic ovary syndrome, hypothyroidism, and acromegaly; (3) Women engaged in various occupations, including driving and working at heights. How to screen OSA in women?Many screening tools and questionnaires can be used to screen for OSA, but should not be used to diagnose OSA in the absence of objective sleep tests. (1) Questionnaires and screening tools: The STOP-Bang questionnaire targeting the general population has higher sensitivity than Berlin Questionnaire (BQ), Epworth Sleepiness Scale (ESS), and others. STOP Bang≥3 points combined with ESS can further improve its specificity and can be used for OSA screening in women. However, the questionnaire has poor sensitivity for female OSA. Type Ⅳ monitoring devices can be used for OSA screening in women with a weak recommendation; (2) PSG is the gold standard for diagnosis. Type Ⅱ or Ⅲ portable monitoring (PM) devices are recommended for the diagnosis of OSA in women in the following conditions: 1) Diagnosis of high-risk OSA patients without complex comorbidities; 2) OSA patients who are immobile or critically ill and unable to undergo PSG monitoring in a sleep center; 3) Diagnosis of perioperative OSA patients; 4) Pregnant women with high suspicion of OSA. How to diagnose OSA in women?The diagnostic and grading criteria for adult non-pregnant women with OSA are the same as the diagnostic criteria for adult OSA; for diagnosis and grading of OSA in pregnant women, see "Section 4: OSA in Pregnancy". How to treat OSA in women?For all the OSA patients with varying degrees of severity in women, the general treatment can be applied: weight loss, dietary control, exercise, position therapy, reduction of alcohol intake, and cautious use of sedative and hypnotic drugs. Medical costs and the risk of comorbidities with OSA in women are higher than those in men. Therefore, OSA patients in women should be promptly evaluated and treated. How to optimize non-invasive positive pressure ventilation (NPPV) treatment and improve compliance for OSA patients in women?(1) NPPV is the first-line treatment for moderate to severe OSA in women. It can relieve upper airway obstruction, eliminate sleep hypoxia, improve sleep quality and quality of life, and reduce the incidence of related complications and mortality; (2) To improve compliance with NPPV treatment, behavioral interventions and patient education are recommended. Selecting an appropriate human-machine interface, improving the humidification effect, promptly handling adverse reactions, and applying remote medical models may improve the compliance. What are the other options for OSA treatment in women?Other treatment methods include oral appliances, upper airway surgery, and sublingual nerve stimulation therapy, which have moderate therapeutic effects in women. Postmenopausal hormone therapy (MHT) in women has a certain therapeutic effect on OSA, but its safety needs further evaluation. What is follow-up evaluation for OSA in women?(1) Follow-up every 6 months or 1 year after receiving NPPV treatment; (2) PSG should be rechecked at the 3rd and 6th months after surgical treatment to evaluate the therapeutic effects. For patients with poor therapeutic effects after surgery, it is recommended to use treatments such as NPPV; (3) PSG should be rechecked at the 3rd and 6th months after oral appliance treatment. Oral appliances should be adjusted as needed to consolidate long-term efficacy, or switched to a treatment such as NPPV; (4) During follow-up, attention should be paid to the improvement of apnea hypopnea index(AHI), symptoms, and side effects; (5) It is recommended that NPPV treatment be remotely managed via the internet, which can provide high-quality and comprehensive sleep care; (6) Follow-up of OSA during pregnancy can be found in "Section 4: OSA in Pregnancy ". How to diagnose and evaluate OSA during pregnancy?OSA during pregnancy has adverse effects on maternal and infant outcomes. It is recommended that high-risk pregnant women be screened and diagnosed for OSA during pregnancy management and healthcare.(1) Screening of the high-risk population: Individuals who meet any of the following criteria are considered at high risk for OSA during pregnancy. 1) Symptoms: snoring during sleep, arousal, headache in the morning, insomnia, depression, excessive daytime sleepiness, and fatigue; 2) Pregnant women over 35 years old; 3) Physical signs: weight exceeding standard body weight by 20% or more, BMI≥28 kg/m, and neck circumference>40 cm; anatomical abnormalities of the upper airways, such as nasal obstruction, tonsil hypertrophy, and mandibular retrognathia, .; 4) Combined internal medicine diseases, such as refractory hypertension, unknown arrhythmia, chronic congestive heart failure, refractory diabetes and insulin resistance, refractory asthma, hypothyroidism, primary aldosteronism; 5) Those with obstetric related diseases, such as preeclampsia, HDP, GDM, and intrauterine growth restriction of the fetus, and with symptoms of chest tightness and apnea that cannot be explained by other factors, and with previous history of gestational OSA or family history.(2) Screening time: There is currently no strong evidence to support the recommendation for optimal screening time. Given the adverse effects of OSA on mothers and infants, it is recommended that high-risk individuals of OSA be screened for OSA between12 and 18 weeks of pregnancy.(3) Screening tools: The main manifestations of OSA in pregnant women are insomnia and poor sleep quality, whereas daytime drowsiness is often not severe. Various sleep questionnaires and models for OSA in pregnancy have poor sensitivity and specificity. Type Ⅳ and consumer-level monitoring devices are lack of sufficient clinical validation. It is recommended that the results of the above screening tools should only have an indicative role in the diagnosis of OSA during pregnancy.(4) Diagnostic tools: PSG is the gold standard for the diagnosis of OSA in pregnancy. PM may be the first choice diagnostic technique for OSA in pregnancy, and Type Ⅲ monitoring devices are the most commonly used devices.(5) Diagnostic criteria: Diagnosis of OSA during pregnancy should be based on symptoms, signs, and PSG or PM monitoring results. Diagnostic criteria for OSA during pregnancy are as follows: 1) PSG or PM monitoring shows AHI≥5 times/h with symptoms or signs of OSA in women, or with related complications (such as diagnosed hypertension, emotional disorders, unexplained arrhythmias, chronic congestive heart failure, HDP, HDM, intrauterine growth restriction that cannot be explained by other factors, chest tightness and apnea excluding other reasons), or with previous history of OSA or family history of OSA; 2) PSG or PM monitoring shows AHI≥10 times/h in those with less daytime drowsiness (ESS≤9 points). How to manage OSA during pregnancy?(1) Once OSA is diagnosed during pregnancy, personalized treatment plans from pregnancy to birth should be developed through collaborative discussions between sleep center professionals, obstetricians, pregnant women, and their families. Multidisciplinary collaboration among anaesthesia, neonatology, and critical care medicine may be required in some cases. A comprehensive management approach should be adopted based on the patient's condition, which includes strengthening weight management, positioning treatment, NPPV treatment, oral appliances, and management of maternal and infant complications; (2) Considering the Regarding continuous weight gain during pregnancy, APAP treatment is more appropriate mode for pregnant women with OSA; (3) Oral appliances are suitable for patients with snoring or mild to moderate OSA, especially those with combined mandibular retraction or NPPV intolerance. However, oral appliances are not recommended as the first-line treatment; (4) It is not recommended to use surgical methods to treat OSA during pregnancy; (5) Follow-up and evaluation: Patients' conditions should be re-evaluated and treatment plans should be adjusted at around 24 weeks of pregnancy. Postpartum PSG or PM monitoring should be repeated to assess the need for continued treatment after delivery.
Topics: Humans; Sleep Apnea, Obstructive; Female; Pregnancy; Pregnancy Complications; Consensus
PubMed: 38858201
DOI: 10.3760/cma.j.cn112147-20240206-00072 -
Molecular Nutrition & Food Research Jun 2024Alcoholic liver disease (ALD) is a global public health concern. Nobiletin, a polymethoxyflavone abundant in citrus fruits, enhances circadian rhythms and ameliorates...
SCOPE
Alcoholic liver disease (ALD) is a global public health concern. Nobiletin, a polymethoxyflavone abundant in citrus fruits, enhances circadian rhythms and ameliorates diet-induced hepatic steatosis, but its influences on ALD are unknown. This study investigates the role of brain and muscle Arnt-like protein-1 (Bmal1), a key regulator of the circadian clock, in nobiletin-alleviated ALD.
METHODS AND RESULTS
This study uses chronic ethanol feeding plus an ethanol binge to establish ALD models in Bmal1 and Bmal1 liver-specific knockout (Bmal1LKO) mice. Nobiletin mitigates ethanol-induced liver injury (alanine aminotransferase [ALT]), glucose intolerance, hepatic apoptosis, and lipid deposition (triglyceride [TG], total cholesterol [TC]) in Bmal1 mice. Nobiletin fails to modulated liver injury (ALT, aspartate aminotransferase [AST]), apoptosis, and TG accumulation in Bmal1LKO mice. The expression of lipogenic genes (acetyl-CoA carboxylase alpha [Acaca], fatty acid synthase [Fasn]) and fatty acid oxidative genes (carnitine pamitoyltransferase [Cpt1a], cytochrome P450, family 4, subfamily a, polypeptide 10 [Cyp4a10], and cytochrome P450, family4, subfamily a, polypeptide 14 [Cyp4a14]) is inhibited, and the expression of proapoptotic genes (Bcl2 inteacting mediator of cell death [Bim]) is enhanced by ethanol in Bmal1 mice. Nobiletin antagonizes the expression of these genes in Bmal1 mice and not in Bmal1LKO mice. Nobiletin activates protein kinase B (PKB, also known as AKT) phosphorylation, increases the levels of the carbohydrate response element binding protein (ChREBP), ACC1, and FASN, and reduces the level of sterol-regulatory element binding protein 1 (SREBP1) and phosphorylation of ACC1 in a Bmal1-dependent manner.
CONCLUSION
Nobiletin alleviates ALD by increasing the expression of genes involved in fatty acid oxidation by increasing AKT phosphorylation and lipogenesis in a Bmal1-dependent manner.
PubMed: 38850176
DOI: 10.1002/mnfr.202300833 -
International Journal of Surgery Case... Jul 2024Brucellosis is a zoonotic illness caused by Brucella bacteria, primarily transmitted through contaminated dairy products or direct contact with infected animals....
INTRODUCTION
Brucellosis is a zoonotic illness caused by Brucella bacteria, primarily transmitted through contaminated dairy products or direct contact with infected animals. Brucellosis is highly prevalent in Iran, with Brucella melitensis biovar 1 being the primary causative agent. Musculoskeletal symptoms, including spondylitis, sacroiliitis, and peripheral arthritis, are common in brucellosis patients, but avascular necrosis of the hip joint is extremely rare.
CASE PRESENTATION
This case report presents a middle-aged woman from Iran with untreated brucellosis infection, who developed rapidly progressing avascular necrosis affecting both hip joints. The patient's social history did not indicate any use of tobacco or alcohol. Furthermore, there was no indication of any traumatic events affecting the patient's hip joints. The patient's family history did not reveal any rheumatologic disorders, and the patient had not been diagnosed with or reported using immune suppressant medications. Laboratory results confirmed that the patient was not diagnosed with sickle cell anemia. The patient had been intolerant to the prescribed medications, Rifampin and Doxycycline. Initially, she presented with severe bilateral hip pain, anorexia, vomiting, periodic chills and fever, myalgia, and night sweats. Pelvis X-ray confirmed bilateral hip avascular necrosis, and total hip arthroplasty was scheduled but subsequently canceled due to persistent brucellosis infection. Physical examination revealed limited hip motion, pain, and inability to bear weight. Laboratory tests indicated leukocytosis, elevated levels of CRP, and high titers on Wright and 2ME tests. Intravenous Ciprofloxacin was initiated, and further investigations were scheduled.
DISCUSSION
Osteoarticular complications are common in individuals with brucellosis. The sacroiliac joints are affected in 80 % of cases, while the spinal joints are affected in 50 %. Brucella-induced arthritis can be found in over 50 % of patients, with the lower limb joints being the most commonly affected. Failure to diagnose and treat hip arthritis caused by brucellosis promptly can lead to severe complications, including dislocation and avascular necrosis of the femoral head. Avascular necrosis is a condition where bone tissue dies due to compromised blood supply. It often remains asymptomatic initially and is usually found incidentally during radiographic imaging. Osteonecrosis of the femoral head can manifest as Legg-Calve-Perthes disease or as a complication of other medical conditions. Various factors can contribute to avascular necrosis, including hip dislocation or fracture, prolonged use of certain medications, excessive alcohol consumption, and certain medical conditions. Magnetic resonance imaging is considered the standard method for diagnosing avascular necrosis. Delay in diagnosing and treating brucellosis can result in permanent bone complications.
CONCLUSION
Brucellosis, a disease prevalent in endemic regions, should be considered as a cause of severe hip pain and other vague symptoms. Timely diagnosis and management are important, especially for high-risk patients with other health conditions and poor drug compliance, to prevent complications such as avascular necrosis.
PubMed: 38843623
DOI: 10.1016/j.ijscr.2024.109808 -
Rice (New York, N.Y.) May 2024Rice is one of the most important food crops in the world, and with the development of direct seeding methods for rice, exposure to anaerobic stress has become a major...
Identification of Key Genes and Pathways for Anaerobic Germination Tolerance in Rice Using Weighted Gene Co-Expression Network Analysis (WGCNA) in Association with Quantitative Trait Locus (QTL) Mapping.
BACKGROUND
Rice is one of the most important food crops in the world, and with the development of direct seeding methods for rice, exposure to anaerobic stress has become a major factor limiting its growth.
RESULTS
In this experiment, we tested the tolerance to anaerobic germination of rice varieties NIP and HD84, and they were used as parents to construct a DH (doubled-haploid) population. The transcriptomes of NIP (highly tolerant) and HD86 (intolerant), and their progeny HR (highly tolerant) and NHR (intolerant) were sequenced from normal and anaerobic environments. The differentially-expressed genes (DEGs) were subjected to GO (Gene ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes), and WGCNA analyses. QTL mapping of the DH population identified tolerance to anaerobic germination-related chromosomal segments. The transcriptome results from 24 samples were combined with the anaerobic stress QTL results for 159 DH population lines to construct a metabolic network to identify key pathways and a gene interaction network to study the key genes. Essential genes were initially subjected to rigorous functional validation, followed by a comprehensive analysis aimed at elucidating their potential utility in domestication and breeding practices, particularly focusing on the exploitation of dominant haplotypes.
CONCLUSION
The results show that pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) are the starting signals of energy metabolism for coleoptile length growth, the auxin transporter EXPA is the determining signal for coleoptile length growth. The pivotal genes Os05g0498700 and Os01g0866100 exert a negative regulatory influence on coleoptile length, ultimately enhancing tolerance to anaerobic germination in rice. Analyses of breeding potential underscore the additional value of Os05g0498700-hyp2 and Os01g0866100-hyp2, highlighting their potential utility in further improving rice through breeding programs. The results of our study will provide a theoretical basis for breeding anaerobic-tolerant rice varieties.
PubMed: 38819744
DOI: 10.1186/s12284-024-00714-y -
Biomedicines May 2024Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and...
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS).
METHODS
This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3-6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab = 31; omalizumab = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS).
RESULTS
ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly ( < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD).
CONCLUSIONS
This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge.
PubMed: 38790987
DOI: 10.3390/biomedicines12051025 -
Molecular Pharmaceutics Jun 2024With the increased prevalence of nonalcoholic steatohepatitis (NASH) in the world, effective pharmacotherapy in clinical practice is still lacking. Previous studies have...
With the increased prevalence of nonalcoholic steatohepatitis (NASH) in the world, effective pharmacotherapy in clinical practice is still lacking. Previous studies have shown that dibenzazepine (DBZ), a Notch inhibitor, could alleviate NASH development in a mouse model. However, low bioavailability, poor water solubility, and extrahepatic side effects restrict its clinical application. To overcome these barriers, we developed a reactive oxygen species (ROS)-sensitive nanoparticle based on the conjugation of bilirubin to poly(ethylene glycol) (PEG) chains, taking into account the overaccumulation of hepatic ROS in the pathologic state of nonalcoholic steatohepatitis (NASH). The PEGylated bilirubin can self-assemble into nanoparticles in an aqueous solution and encapsulate insoluble DBZ into its hydrophobic cavity. DBZ nanoparticles (DBZ Nps) had good stability, rapidly released DBZ in response to HO, and effectively scavenged intracellular ROS of hepatocytes. After systemic administration, DBZ Nps could accumulate in the liver of the NASH mice, extend persistence in circulation, and improve the bioavailability of DBZ. Furthermore, DBZ Nps significantly improved glucose intolerance, relieved hepatic lipid accumulation and inflammation, and ameliorated NASH-induced liver fibrosis. Additionally, DBZ Nps had no significant extrahepatic side effects. Taken together, our results highlight the potential of the ROS-sensitive DBZ nanoparticle as a promising therapeutic strategy for NASH.
Topics: Animals; Non-alcoholic Fatty Liver Disease; Reactive Oxygen Species; Mice; Nanoparticles; Lipogenesis; Mice, Inbred C57BL; Male; Liver; Receptors, Notch; Humans; Inflammation; Bilirubin; Polyethylene Glycols; Disease Models, Animal; Hepatocytes; Dibenzazepines
PubMed: 38751169
DOI: 10.1021/acs.molpharmaceut.4c00070 -
Nutrients Apr 2024Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether...
Prenatal Choline Supplementation Improves Glucose Tolerance and Reduces Liver Fat Accumulation in Mouse Offspring Exposed to Ethanol during the Prenatal and Postnatal Periods.
Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether postnatal AE exacerbates metabolic deterioration resulting from prenatal AE. Choline is a semi-essential nutrient that has been demonstrated to mitigate the cognitive impairment of prenatal AE. This study investigated how maternal choline supplementation (CS) may modify the metabolic health of offspring with prenatal and postnatal AE (AE/AE). C57BL/6J female mice were fed either a Lieber-DeCarli diet with 1.4% ethanol between embryonic day (E) 9.5 and E17.5 or a control diet. Choline was supplemented with 4 × concentrations versus the control throughout pregnancy. At postnatal week 7, offspring mice were exposed to 1.4% ethanol for females and 3.9% ethanol for males for 4 weeks. AE/AE increased hepatic triglyceride accumulation in male offspring only, which was normalized by prenatal CS. Prenatal CS also improved glucose tolerance compared to AE/AE animals. AE/AE suppressed hepatic gene expression of peroxisome proliferator activated receptor alpha () and low-density lipoprotein receptor (), which regulate fatty acid catabolism and cholesterol reuptake, respectively, in male offspring. However, these changes were not rectified by prenatal CS. In conclusion, AE/AE led to an increased risk of steatosis and was partially prevented by prenatal CS in male mice.
Topics: Animals; Female; Pregnancy; Choline; Ethanol; Male; Dietary Supplements; Liver; Prenatal Exposure Delayed Effects; Mice, Inbred C57BL; Mice; Fatty Liver; Triglycerides; PPAR alpha; Receptors, LDL; Glucose Intolerance; Lipid Metabolism
PubMed: 38732511
DOI: 10.3390/nu16091264 -
American Journal of Physiology.... Jun 2024Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright...
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CB) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.8 yr). All patients with ME/CFS had postural tachycardia syndrome (POTS). A 10-min 60° head-up tilt (HUT) significantly increased heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, < 0.05) and decreased end-tidal CO (ETCO; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, < 0.05) in ME/CFS versus control. In ME/CFS, HUT significantly decreased CB compared with control (-22.5% vs. -8.7%, < 0.005). To mitigate the orthostatic CB reduction, we administered supplemental CO, phenylephrine, and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct = 4 N-back during HUT in ME/CFS similar to control (ME/CFS = 38.5 ± 5.5 vs. ME/CFS + PE= 65.6 ± 5.7 vs. Control 56.9 ± 7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. Although CO and acetazolamide had no effect on PhSI in ME/CFS, phenylephrine caused a significant reduction in PhSI (ME/CFS = 0.80 ± 0.03 vs. ME/CFS + PE= 0.69 ± 0.04, < 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in patients with ME/CFS, perhaps related to improved neurovascular coupling, cerebral autoregulation, and maintenance of CB. We evaluated cognitive function before and after CO, acetazolamide, and phenylephrine, which mitigate orthostatic reductions in cerebral blood velocity. Neither CO nor acetazolamide affected N-back testing (% correct answers) during an orthostatic challenge. Only phenylephrine improved upright N-back performance in ME/CFS, as it both blocked hyperventilation and increased CO significantly compared with those untreated. And only phenylephrine resulted in improved PSI values in both ME/CFS and control while upright, suggesting improved cerebral autoregulation.
Topics: Humans; Cerebrovascular Circulation; Phenylephrine; Female; Male; Orthostatic Intolerance; Adult; Young Adult; Blood Flow Velocity; Blood Pressure; Fatigue Syndrome, Chronic; Tilt-Table Test; Cognition; Homeostasis; Case-Control Studies; Heart Rate; Arterial Pressure; Postural Orthostatic Tachycardia Syndrome
PubMed: 38682242
DOI: 10.1152/ajpregu.00071.2024