The continuum of disrupted metabolic tempo, mitochondrial substrate congestion, and metabolic gridlock toward the development of non-communicable diseases.

Non-communicable diseases (NCD) are the slow-motion disasters with imminent global health care burden. The current dietary management for NCD is dominated by the calorie balance model. Apart from the quantitative balance of calorie, healthy bioenergetics requires temporal eating and fasting rhythms, and the subsequent switching for different metabolic fuels. We herein term these three bioenergetic attributes, i.e., caloric balance, diurnal eating-fasting rhythm, and metabolic flexibility, as the metabolic tempo. These three attributes are intertwined with each other; alteration of one attribute affects one or more other attributes. Lifestyle-induced disrupted metabolic tempo presents a high flux of mixed carbon substrates to mitochondria, with the resulting congestion and indecisiveness of metabolic switches. Such indecisiveness impairs metabolic flexibility, promotes anabolism, and accumulates the energy storage pools. The triggers from hypoxic inducible factor expression could further promote the metabolic gridlock and adipocyte maladaptation. The maladaptive adipocytes lead to ectopic fat deposition, increased circulating lipid levels, insulin resistance, and chronic systemic inflammation. These continuum set stages for clinical NCDs. We propose that the restoration of all tempo attributes through the combined diet-, time-, and calorie-restricted interventions could be the preferred strategy for NCD management.

The microbiota-mediated dietary and nutritional interventions for COVID-19.

Worldwide, scientists are looking for specific treatment for COVID-19. Apart from the antiviral approach, the interventions to support healthy immune responses to the virus are feasible through diet, nutrition, and lifestyle approaches. This narrative review explores the recent studies on dietary, nutritional, and lifestyle interventions that influence the microbiota-mediated immunomodulatory effects against viral infections. Cumulative studies reported that the airway microbiota and SARS-CoV-2 leverage each other and determine the pathogen-microbiota-host responses. Cigarette smoking can disrupt microbiota abundance. The composition and diversification of intestinal microbiota influence the airway microbiota and the innate and adaptive immunity, which require supports from the balance of macro- and micronutrients from the diet. Colorful vegetables supplied fermentable prebiotics and anti-inflammatory, antioxidant phytonutrients. Fermented foods and beverages support intestinal microbiota. In sensitive individuals, the avoidance of the high immunoreactive food antigens contributes to antiviral immunity. This review suggests associations between airway and intestinal microbiota, antiviral host immunity, and the influences of dietary, nutritional, and lifestyle interventions to prevent the clinical course toward severe COVID-19.

Restoration of metabolic tempo through time-restricted eating (TRE) as the preventive measure for metabolic diseases.

The characteristics of healthy bioenergetics are the overall balance of energy intake and expenditure, the alternate switching for different metabolic fuels, and the temporal rhythm of eating and fasting. These three bioenergetic attributes, herein, are termed as the metabolic tempo. Cumulative studies revealed the beneficial health effects of fasting. Most of the fasting regimens harness their innate mechanisms of enhancing metabolic fuel switching, thus improving metabolic flexibility. The emerging time-restricted eating (TRE) regimen includes the restoration of diurnal eating and fasting rhythms, improve the metabolic flexibility, while spontaneously reduces the food intake despite the ad-libitum eating. TRE thus simultaneously improves all three bioenergetic-tempo attributes when compared to the energy balance control in general obesity control. We reviewed fifteen human studies of TRE and TRE-liked interventions from 2007 to 2019. These studies reported promising beneficial metabolic effects on body weight, glycemic, and lipid controls while demonstrating most of the fasting-related metabolic and epigenetic responses in overweight and obese individuals. TRE is practically possible for long-termed implementation. Despite its potentials to restore the underlying dysregulated bioenergetics., there is no study confirming that TRE could prevent the development of common metabolic diseases in healthy subjects after long-term implementation. This gap of knowledge warrants future investigation.

Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic.

It is an ugly fact that a significant amount of the world's population will contract SARS-CoV-II infection with the current spreading. While a specific treatment is not yet coming soon, individual risk assessment and management strategies are crucial. The individual preventive and protective measures drive the personal risk of getting the disease. Among the virus-contracted hosts, their different metabolic status, as determined by their diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors, govern the personal fate toward different clinical severity of COVID-19, from asymptomatic, mild, moderate, to death. The careful individual assessment for the possible dietary, nutritional, medical, lifestyle, and environmental risks, together with the proper relevant risk management strategies, is the sensible way to deal with the pandemic of SARS-CoV-II.

Micronutrients as immunomodulatory tools for COVID-19 management.

COVID-19 rapidly turned to a global pandemic posing lethal threats to overwhelming health care capabilities, despite its relatively low mortality rate. The clinical respiratory symptoms include dry cough, fever, anosmia, breathing difficulties, and subsequent respiratory failure. No known cure is available for COVID-19. Apart from the anti-viral strategy, the supports of immune effectors and modulation of immunosuppressive mechanisms is the rationale immunomodulation approach in COVID-19 management. Diet and nutrition are essential for healthy immunity. However, a group of micronutrients plays a dominant role in immunomodulation. The deficiency of most nutrients increases the individual susceptibility to virus infection with a tendency for severe clinical presentation. Despite a shred of evidence, the supplementation of a single nutrient is not promising in the general population. Individuals at high-risk for specific nutrient deficiencies likely benefit from supplementation. The individual dietary and nutritional status assessments are critical for determining the comprehensive actions in COVID-19.

Developmental toxicity of arsenic: a drift from the classical dose-response relationship.

Arsenic is a well-known natural environmental contaminant distributed in food, water, air, and soil. The developmental toxicity of arsenic exposure is a significant concern in large parts of the world. Unlike acute toxic exposure, the classical dose-response relationship is not adequate for estimating the possible impact of chronic low-level arsenic exposure. The real-life risk and impact assessments require the consideration of the co-exposure to multiple toxins, individual genetic and nutritional predisposition, and the particularly vulnerable stages of the neurodevelopment. This context shifts the assessment model away from the 'one-exposure-for-one-health-effect.' We underscore the need for a comprehensive risk assessment that takes into account all relevant determinants. We aim to elaborate a model that can serve as a basis for an understanding of complex interacting factors in a long-lasting and ongoing low-level arsenic exposure, to identify, protect, and support the children at risk.

Early-Life Lead Exposure: Risks and Neurotoxic Consequences.

Lead (Pb) does not have any biological function in a human, and there is likely no safe level of Pb in the human body. The Pb exposure impacts are a global concern for their potential neurotoxic consequences. Despite decreasing both the environmental Pb levels and the average blood Pb levels in the survey populations, the lifetime redistribution from the tissues-stored Pb still poses neurotoxic risks from the low-level exposure in later life. The growing fetus and children hold their innate high-susceptible to these Pb-induced neurodevelopmental and neurobehavioral effects. This article aims to evaluate the cumulative studies and insights on the topic of Pb neurotoxicology while assessing the emerging trends in the field. The Pb-induced neurochemical and neuro-immunological mechanisms are likely responsible for the high-level Pb exposure with the neurodevelopmental and neurobehavioral impacts at the initial stages. Early-life Pb exposure can still produce neurodegenerative consequences in later life due to the altered epigenetic imprints and the ongoing endogenous Pb exposure. Several mechanisms contribute to the Pb-induced neurotoxic impacts, including the direct neurochemical effects, the induction of oxidative stress and inflammation through immunologic activations, and epigenetic alterations. Furthermore, the individual nutritional status, such as macro-, micro-, or antioxidant nutrients, can significantly influence the neurotoxic impacts even at low-level exposure to Pb. The prevention of early-life Pb exposure is, therefore, the critical determinant for alleviating various Pb-induced neurotoxic impacts across the different age groups.

Traditional Chinese Medicine as the preventive and therapeutic remedy for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic still has tremendous impacts on the global socio-economy and quality of living. The traditional Chinese Medicines (TCM) approach showed encouraging results during previous outbreaks of Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). With limited treatment availability, TCM herbs and formulations could be viable to reduce COVID-19 symptoms and potential sources for discovering novel therapeutic targets. We reviewed 12 TCM herbs and formulations recommended for COVID-19 management by the National Health Commission and National Administration of Traditional Chinese Medicine, the People's Republic of China. This article explored the Chinese national authorities' guidelines from 2003 to 2020, the scientific data in public databases for the recommended TCM remedies, and their potential mechanistic actions in COVID-19 management. Several TCM herbs and formulations could potentially benefit COVID-19 management. The recommended TCM oral preparations list are Huoxiang zhengqi, Jinhua Qinggan, Lianhua Qingwen, and Shufeng jiedu; the recommended injection preparations comprise Xiyanping Xuebijing, Re-Du-Ning, Tanreqing, Xingnaojing, Shenfu, Shengmai, and Shenmai. TCM remedies are viable options for symptom alleviation and management of COVID-19. The current SARS-CoV-2 pandemic presents an opportunity to find novel therapeutic targets from TCM-active ingredients. Despite the recommendations in Chinese National guidelines, these remedies warrant further assessments in well-designed clinical trials for their efficacies in COVID-19.

Metabolic Conditions and Peri-Implantitis.

Dental implants to replace lost teeth are a common dentistry practice nowadays. Titanium dental implants display a high success rate and improved safety profile. Nevertheless, there is an increasing peri-implantitis (PI), an inflammatory disease associated with polymicrobial infection that adversely affects the hard and soft tissues around the implant. The present review highlights the contribution of different metabolic conditions to PI. The considerations of both local and systemic metabolic conditions are crucial for planning successful dental implant procedures and during the treatment course of PI. Un- or undertreated PI can lead to permanent jaw bone suffering and dental implant losses. The common mediators of PI are inflammation and oxidative stress, which are also the key mediators of most systemic metabolic disorders. Chronic periodontitis, low-grade tissue inflammation, and increased oxidative stress raise the incidence of PI and the underlying systemic metabolic conditions, such as obesity, diabetes mellitus, or harmful lifestyle factors (cigarette smoking, etc.). Using dental biomaterials with antimicrobial effects could partly solve the problem of pathogenic microbial contamination and local inflammation. With local dentistry considering factors, including oral microbiota and implant quality control, the inclusion of the underlying systemic metabolic conditions into the pre-procedure planning and during the treatment course should improve the chances of successful outcomes.

Combined Supplementation of Coenzyme Q10 and Other Nutrients in Specific Medical Conditions.

Coenzyme Q10 (CoQ10) is a compound with a crucial role in mitochondrial bioenergetics and membrane antioxidant protection. Despite the ubiquitous endogenous biosynthesis, specific medical conditions are associated with low circulating CoQ10 levels. However, previous studies of oral CoQ10 supplementation yielded inconsistent outcomes. In this article, we reviewed previous CoQ10 trials, either single or in combination with other nutrients, and stratified the study participants according to their metabolic statuses and medical conditions. The CoQ10 supplementation trials in elders reported many favorable outcomes. However, the single intervention was less promising when the host metabolic statuses were worsening with the likelihood of multiple nutrient insufficiencies, as in patients with an established diagnosis of metabolic or immune-related disorders. On the contrary, the mixed CoQ10 supplementation with other interacting nutrients created more promising impacts in hosts with compromised nutrient reserves. Furthermore, the results of either single or combined intervention will be less promising in far-advanced conditions with established damage, such as neurodegenerative disorders or cancers. With the limited high-level evidence studies on each host metabolic category, we could only conclude that the considerations of whether to take supplementation varied by the individuals' metabolic status and their nutrient reserves. Further studies are warranted.

The Proteomics Study of Compounded HFE/TF/TfR2/HJV Genetic Variations in a Thai Family with Iron Overload, Chronic Anemia, and Motor Neuron Disorder.

The mutation of the homeostatic iron regulatory genes (HFE) impaired the hepatic hepcidin transcription leading to the chronic excess of the iron pool, with the adverse consequences of free radical oxidative damages. We herein reported the findings of Thai family members who had the compound of uncommon HFE rs2794719, together with transferrin (TF) rs1867504, transferrin receptor 2 (TfR2) rs7385804, and hemojuvelin (HJV) rs16827043 genetic variants involved in the hepcidin transcriptional pathway. These compounded genetic variants could produce the spectrum of clinical phenotypes that spanned from mild to moderate symptoms of chronic anemia to an established motor neuron disorder. The feasible pathophysiologies were the impairment of the transferrin receptor functions, which affected the endocytic uptake of halo-transferrin into the erythroblast precursors. Such a defect left the erythropoiesis depleted of their iron supply. These alterations also promoted the TfR-independent uptake of iron into other target tissues and left the TrF2/BMP-dependent-hepcidin activation pathway unattended. We used the predicted molecular interactive proteomes to support our speculated dysregulated iron metabolism. During the early stage of an elevated ferritin level, there was no inhibition of ferroportin activities from hepcidin. These pathophysiological processes went on to the point of an iron overload threshold. After that, the hepcidin transcription started to kick in with the resulting decreased serum iron levels and deterioration of clinical symptoms.

Individual risk management strategy for SARS-CoV-2 infection: A step toward personalized healthcare.

Lethal or critical COVID-19 occurs most in infected hosts with certain risk factors such as advanced age or pre-existing disease. Host metabolic status significantly affects the clinical presentations of SARS-CoV-2 infection. Individual risk management is thus crucial for preventing severe COVID-19. Such susceptibility is individual, depending on a multitude of factors. Personalized risk assessment requires the inclusive analysis of big health data to stratify individual risk and derive a customized action plan. Personalized medicine requires shifting from the virology aspect per se to the whole individual's consideration, including dietary pattern, nutritional status, supporting lifestyle, co-existing diseases, and environmental factors. In this short communication, we discuss the individual management strategy for SARS-CoV2 infection as a step towards future personalized healthcare.

The Roles of Dietary, Nutritional and Lifestyle Interventions in Adipose Tissue Adaptation and Obesity.

The obesity and the associated non-communicable diseases (NCDs) are globally increasing in their prevalence. While the modern-day lifestyle required less ventilation of metabolic energy through muscular activities, this lifestyle transition also provided the unlimited accession to foods around the clock, which prolong the daily eating period of foods that contained high calorie and high glycemic load. These situations promote the high continuous flux of carbon substrate availability in mitochondria and induce the indecisive bioenergetic switches. The disrupted bioenergetic milieu increases the uncoupling respiration due to the excess flow of the substrate-derived reducing equivalents and reduces ubiquinones into the respiratory chain. The diversion of the uncoupling proton gradient through adipocyte thermogenesis will then alleviate the damaging effects of free radicals to mitochondria and other organelles. The adaptive induction of white adipose tissues (WAT) to beige adipose tissues (beAT) has shown beneficial effects on glucose oxidation, ROS protection and mitochondrial function preservation through the uncoupling protein 1 (UCP1)-independent thermogenesis of beAT. However, the maladaptive stage can eventually initiate with the persistent unhealthy lifestyles. Under this metabolic gridlock, the low oxygen and pro-inflammatory environments promote the adipose breakdown with sequential metabolic dysregulation, including insulin resistance, systemic inflammation and clinical NCDs progression. It is unlikely that a single intervention can reverse all these complex interactions. A comprehensive protocol that includes dietary, nutritional and all modifiable lifestyle interventions, can be the preferable choice to decelerate, stop, or reverse the NCDs pathophysiologic processes.

Neurological Involvements of SARS-CoV2 Infection.

COVID-19 is a pandemic viral infection caused by a novel coronavirus, SARS-CoV2, which is a global concern of the twenty-first century for its rapid spreading in a short period. Apart from its known acute respiratory involvements, the CNS manifestations of COVID-19 are common. These neurological symptoms are diverse and could range from mild nonspecific or specific symptoms such as the loss of various sensory perceptions, the worrying autoimmune Guillain-Barré syndrome, to the life-threatening acute disseminated encephalomyelitis, and the CNS-mediated respiratory distress. An autopsy report documented the presence of SARS-CoV2 in brain tissues of a COVID-19 patient. However, there is no definite conclusion on the mechanisms of SARS-CoV2 neuroinvasion. These proposed mechanisms include the direct viral invasion, the systemic blood circulation, or the distribution of infected immune cells. Concerning these different neuropathophysiologies, COVID-19 patients who are presenting with either the early-onset, multiple, and severe CNS symptoms or rapid respiratory deterioration should be suspected for the direct viral neuroinvasion, and appropriate management options should be considered. This article reviews the neurological manifestations, the proposed neuroinvasive mechanisms, and the potential neurological sequelae of SARS-CoV2.

Prevalence and Factors Associated with High Levels of Aluminum, Arsenic, Cadmium, Lead, and Mercury in Hair Samples of Well-Nourished Thai Children in Bangkok and Perimeters.

Toxic element exposure increases risk of neurodevelopmental disorders. However, hair element profiles of well-nourished urban resident children were largely unknown. We identified prevalence and the contributing factors of high hair aluminum (Al), arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) levels in 111 Thai children (aged 3-7 years old). Most participants were well-nourished with high socioeconomic status. Since ROC curve of hair element data showed inadequate sensitivity for cutoff set-up, US reference hair levels were used to categorize high and low level groups. Nevertheless, compared to the current reference at 5 µg/dL, blood lead cutoff at 2.15 µg/dL provided more consistent results with that of hair lead levels. High As and Pb levels were the first and second most prevalent element, while Al was the element found in highest amount in hair. High hair Al (12% prevalence) levels were associated with being male regardless of age or nutritional status. High hair As levels were associated with living in Bangkok (OR = 6.57) regardless of school type. High hair Pb levels were associated with being under 5 years old and living in Bangkok (OR = 3.06). However, no associations were found between blood Pb, hair Cd, Hg, and tested factors. These findings suggested that under 5-year-old boys living in capital city like Bangkok may be at risk of exposure to multiple toxic elements. Future studies in these children are warranted to identify their exposure sources and proper risk management strategies.

Hair Zinc and Severity of Symptoms Are Increased in Children with Attention Deficit and Hyperactivity Disorder: a Hair Multi-Element Profile Study.

Determination of bioelement levels in hair is an emerging non-invasive approach for screening bioelement deposition. However, the role of essential bioelement levels in hair and attention deficit/hyperactivity disorder (ADHD) risk or severity is largely unknown. In this study, we have compared multi-element hair profiles between healthy and ADHD Thai children. In addition, the correlations between bioelements and ADHD symptoms according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition, diagnostic criteria were identified. A case-control study was conducted in 111 Thai children (45 newly diagnosed ADHD and 66 matched healthy), aged 3-7 years, living in Bangkok and suburban areas. Levels of 39 bioelements in hair were measured by ICP-MS. Among the analyzed bioelements, Cu/Zn and P/Zn ratios in ADHD children were significantly lower than those in healthy children. Indeed, increased hair Zn level was correlated with more symptoms of inattention, hyperactivity, and total ADHD symptoms. Higher Zn content was also associated with being female and older age. Furthermore, Zn in hair was positively correlated with levels of Ca, Mg, and P; however, it showed a negative correlation with Al, As, Fe, and Mo. These findings warrant further confirmation in a large-scale study. Thai Clinical Trials Registry (TCTR) study ID: 20151113001.