Lactate promotes fatty acid oxidation by the tricarboxylic acid cycle and mitochondrial respiration in muscles of obese mice.

Lower oxidative capacity in skeletal muscles (SKMs) is a prevailing cause of metabolic diseases. Exercise not only enhances the fatty acid oxidation (FAO) capacity of SKMs but also increases lactate levels. Given that lactate may contribute to tricarboxylic acid cycle (TCA) flux and impact monocarboxylate transporter 1 in the SKMs, we hypothesize that lactate can influence glucose and fatty acid (FA) metabolism. To test this hypothesis, we investigated the mechanism underlying lactate-driven FAO regulation in the SKM of mice with diet-induced obesity (DIO). Lactate was administered to DIO mice immediately after exercise for over 3 wk. We found that increased lactate levels enhanced energy expenditure mediated by fat metabolism during exercise recovery and decreased triglyceride levels in DIO mice SKMs. To determine the lactate-specific effects without exercise, we administered lactate to mice on a high-fat diet (HFD) for 8 wk. Similar to our exercise conditions, lactate increased FAO, TCA cycle activity, and mitochondrial respiration in the SKMs of HFD-fed mice. In addition, under sufficient FA conditions, lactate increased uncoupling protein-3 abundance via the NADH-NAD+ shuttle. Conversely, ATP synthase abundance decreased in the SKMs of HFD mice. Taken together, our results suggest that lactate amplifies the adaptive increase in FAO capacity mediated by the TCA cycle and mitochondrial respiration in SKMs under sufficient FA abundance.NEW & NOTEWORTHY Lactate administration post-exercise promotes triglyceride content loss in skeletal muscles (SKMs) and reduced body weight. Lactate enhances fatty acid oxidation in the SKMs of high-fat diet (HFD)-fed mice due to enhanced mitochondrial oxygen consumption. In addition, lactate restores the malate-aspartate shuttle, which is reduced by a HFD, and activates the tricarboxylic acid cycle (TCA) cycle in SKMs. Interestingly, supraphysiological lactate facilitates uncoupling protein-3 expression through NADH/NAD+, which is enhanced under high-fat levels in SKMs.

High-molecular-weight Fucoidan exerts an immune-enhancing effect in RAW 264.7 cells and cyclophosphamide-induced immunosuppression rat by altering the gut microbiome.

High-molecular-weight fucoidan (Fucoidan P), sourced from Undaria pinnatifida exhibits several health benefits, including immunomodulation. However, the mechanisms underlying the immune-enhancing effects of Fucoidan P remain unclear. Here, we investigated the immune-enhancing effects and the potential mechanisms of Fucoidan P using RAW 264.7 macrophages and cyclophosphamide (CP)-induced immunosuppression rat model. In macrophages, Fucoidan P showed dose-dependent stimulation by increasing cell proliferation, nitric oxide production, and gene expression of inducible nitric oxide synthase, cyclooxygenase-2, and proinflammatory cytokines. These effects are mediated through the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Moreover, orally administered Fucoidan P was evaluated in immunosuppressed rats treated with CP. Fucoidan P administration increased hematological values and natural killer cell activity, and positively affected nitrite and prostaglandin E2 levels. The Fucoidan P treatment groups exhibited improved serum cytokine levels as well as splenic and intestinal cytokine mRNA expression compared to the model group. Fucoidan P also mitigated splenic damage and increased the phosphorylation of NF-κB and NF-κB inhibitor alpha (IκBα). Furthermore, Fucoidan P treatment altered the gut microbiota composition, enhancing the alpha diversity, evenness, and abundance of Bacteroidetes, which are associated with immune function. Taken together, our findings suggest that Fucoidan P exerts beneficial effects on immune function by activating NF-κB and modulating gut microbiota. These findings suggested its potential as a therapeutic agent for immune enhancement.

Causative Activities and Prognostic Factors of Open-Globe Injury: A Registry-Based City-Wide Multicentre Study.

PURPOSE: Traumatic globe injury is classified into closed-globe and open-globe injury (OGI); OGI leads to a worse prognosis. We aimed to identify causative activities and prognostic factors of OGI in a metropolitan city in South Korea. METHODS: This retrospective observational study used a prospective eye-injury registry conducted in Daegu, South Korea, between 1 August 2016 and 31 July 2021. We identified epidemiology and visual outcomes of OGI at four tertiary hospitals. Those with the best visual acuity lower than counting fingers at the 6-month follow-up were considered to have poor visual outcome. RESULTS: Of 9,208 patients with eye injuries, 282 had OGI. Most OGI patients were male (261, 92.6%), with the largest proportion in their 50s (76, 27.0%). The most frequent causative activity was mowing (59, 20.9%), and poor visual outcome was most seen in assault (7, 87.5%) and sports activity (9, 81.8%). Hammering, metal work, and sports activity were prevalent in those under 30, and mowing was most prevalent in those in their 50s (16, 21.1%) and 60s (29, 40.3%). In the multivariable logistic regression analysis, OGI related to traffic accident and sports activity were presented poor prognosis (adjusted odds ratio [aOR] 13.259, 95% confidence interval [CI] 1.202-146.205 for traffic accident; aOR 6.801, 95% CI 1.064-43.487 for sports activity). CONCLUSION: We need to develop advanced vehicle safety equipment, implement public education promoting seat belt usage and hazards of OGI, establish eye protection standards for key causal activities, and provide eye protection equipment for sports activities and mowing.

The obesogen bisphenol A promotes adipogenesis in canine adipose-derived stem cells: Potential implication in dog obesity.

The growing number of companion dogs has contributed to a rapidly growing market for pet products, including dog toys. However, little is known about the hazardous substances released from dog toys. This study aims to examine the potential presence of obesogens, a subset of endocrine-disrupting chemicals (EDCs) that are widely utilized as raw materials in the manufacture of dog toy components, and their effects on dog health. To achieve this, we adapted and employed a migration method typically used for children's products to simulate obesogen exposure in dogs through sucking or chewing toys. We demonstrated that out of various obesogens, bisphenol A (BPA) was released from dog toys into synthetic saliva, whereas phthalates and azo dyes were not detected in any of the leachates. Additionally, we found that BPA induced adipogenic differentiation in canine adipose-derived stem cells (cADSCs). Our RNA sequencing experiments revealed that BPA alters the adipogenesis-related gene signature in cADSCs by elevating the expression levels of ADIPOQ, PLIN1, PCK1, CIDEC, and FABP4. The associated transcriptional changes are involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which may contribute to the promotion of adipogenesis by BPA. Our findings suggest that companion dogs are at risk of BPA exposure, which may contribute to obesity in dogs. Therefore, the implementation of precautionary measures is crucial.

Comparative study on estrogen receptor alpha dimerization and transcriptional activity of parabens.

Parabens are used as preservatives in various household products, including oral products, cosmetics, and hair/body washes. In recent years, the widespread use of parabens has raised concerns due to the potential health risks associated with their estrogenic effects. In the present study, we evaluated and compared the estrogenic activity of parabens using two cell-based in vitro tests: (1) bioluminescence resonance energy transfer (BRET)-based estrogen receptor alpha (ERα) dimerization using HEK293 cells that were stably transfected with ERα-fused NanoLuc luciferase (Nluc) and HaloTag (HT) expression vector, and (2) stably transfected transcriptional activation (STTA) assays using ERα-HeLa9903 cells. The following parabens were tested using the BRET-based ERα dimerization assay and showed estrogenic activity (PC20 values): methyl paraben (MP, 5.98 × 10-5 M), ethyl paraben (EP, 3.29 × 10-5 M), propylparaben (PP, 3.09 × 10-5 M), butyl paraben (BP, 2.58 × 10-5 M), isopropyl paraben (IsoPP, 1.37 × 10-5 M), and isobutyl paraben (IsoBP, 1.43 × 10-5 M). Except MP, all other parabens tested using the STTA assay also showed estrogenic activity: EP, 7.57 × 10-6 M; PP, 1.18 × 10-6 M; BP, 3.02 × 10-7 M; IsoPP, 3.58 × 10-7 M; and IsoBP, 1.80 × 10-7 M. Overall, EP, PP, BP, IsoPP, and IsoBP tested positive for estrogenic activity using both assays. These findings demonstrate that most parabens, albeit not all, induce ERα dimerization and possess estrogenic activity.

Prehospital factors associated with out-of-hospital cardiac arrest outcomes in a metropolitan city: a 4-year multicenter study.

BACKGROUND: Prehospital factors play a vital role in out-of-hospital cardiac arrest (OHCA) survivability, and they vary between countries and regions. We investigated the prehospital factors associated with OHCA outcomes in a single metropolitan city in the Republic of Korea. METHODS: This study included adult medical OHCA patients enrolled prospectively, using data from the citywide OHCA registry for patients registered between 2018 and 2021. The primary outcome was survival to hospital discharge. Multivariable logistic regression analysis was conducted to determine the factors associated with the study population's clinical outcomes, adjusting for covariates. We performed a sensitivity analysis for clinical outcomes only for patients without prehospital return of spontaneous circulation prior to emergency medical service departure from the scene. RESULTS: In multivariable logistic regression analysis, older age (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.95-0.97), endotracheal intubation (adjusted odds ratio [aOR] 0.29; 95% [CIs] 0.17-0.51), supraglottic airway (aOR 0.29; 95% CI 0.17-0.51), prehospital mechanical chest compression device use (OR 0.13; 95% CI 0.08-0.18), and longer scene time interval (OR 0.96; 95% CI 0.93-1.00) were negatively associated with survival. Shockable rhythm (OR 24.54; 95% CI 12.99-42.00), pulseless electrical activity (OR 3.11; 95% CI 1.74-5.67), and witnessed cardiac arrest (OR 1.59; 95% CI 1.07-2.38) were positively associated with survival. In the sensitivity analysis, endotracheal intubation, supraglottic airway, prehospital mechanical chest compression device use, and longer scene time intervals were associated with significantly lower survival to hospital discharge. CONCLUSIONS: Regional resuscitation protocol should be revised based on the results of this study, and modifiable prehospital factors associated with lower survival of OHCA should be improved.

Perfluorinated compounds in adults and their association with fasting glucose and incident diabetes: a prospective cohort study.

BACKGROUND: The endocrine disruption of perfluorinated compounds is an emerging issue. We aimed to examine the association of serum perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels with incident diabetes and fasting serum glucose concentration. METHODS: This prospective cohort study was based on an urban-based cohort subpopulation from the Korean Genome and Epidemiology Study. Serum samples (600 µL) were received from 100 participants in the normoglycemic baseline survey (2004-2013), and concentrations of PFOA and PFOS were measured using mass spectrometry. The incidence of diabetes was tracked in the follow-up survey (2012-2016). RESULTS: The mean age was 56.4 years (men, 59%). The median serum PFOA and PFOS concentrations were 4.29 ng/mL and 9.44 ng/mL, respectively. PFOA and PFOS concentrations differed according to age, sex, and residential area. After 60 months, 23 patients had diabetes. Log-transformed PFOA (lnPFOA) and log-transformed PFOS (lnPFOS) were significantly higher in those who transitioned to diabetes than in those who did not (both p < 0.05). After multivariate adjustment, lnPFOA (coefficient = 6.98, 95% CI -0.04-14, p = 0.054) and lnPFOS (coefficient = 7.06, 95% CI -0.96-15.08, p = 0.088) predicted increased fasting glucose without statistical significance. In addition, lnPFOA, but not lnPFOS, significantly predicted incident diabetes (HR = 3.98, 95% CI 1.42-11.1, p < 0.01). CONCLUSION: Exposure to PFOA and PFOS may have a potential dysglycemic effect. In particular, exposure to PFOA increased the risk of diabetes. Further research with larger sample size is warranted.

Human Evidence of Perfluorooctanoic Acid (PFOA) Exposure on Hepatic Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Perfluorooctanoic acid (PFOA) is widely used throughout different industries, including the food industry, because it is resistant to heat and prevents water or oil from easily permeating into or contaminating materials coated by PFOA. Although many studies have reported an association between PFOA exposure and the risk of developing hepatic diseases, it is still in debate because they have shown conflicting results. Therefore, this study conducted a systematic review and meta-analysis on the relationship between PFOA exposure and hepatic diseases. METHODS: This study searched studies related to hepatic diseases due to PFOA exposure until 31 December 2021, using PubMed, EMBASE, and Web of Science. This study performed a systematic review and meta-analysis through research question development, literature screening, data extraction, and risk of bias evaluation. This study found 8280 studies after excluding duplicate literature and selected 5 studies in the final stage. Among them, two studies were included in the meta-analysis. RESULTS: The results of the meta-analysis showed that the ALT of people exposed to PFOA was 117% higher than the ALT of those not exposed to PFOA, and it was significantly different (OR = 1.167; 95% CI, 1.086-1.254). CONCLUSION: However, since the number of studies included in the analysis was not large enough to conclude that PFOA exposure was associated with the development of hepatic diseases, more observational studies are needed to confirm its long-term effects.

Evaluation of the Public Health Emergency Response to the COVID-19 Pandemic in Daegu, Korea During the First Half of 2020.

OBJECTIVES: This study evaluated the response in Daegu, Korea to the first wave of the coronavirus disease 2019 (COVID-19) pandemic according to a public health emergency response model. METHODS: After an examination of the official data reported by the city of Daegu and the Korea Centers for Disease Control and Prevention, as well as a literature review and advisory meetings, we chose a response model. Daegu's responses were organized into 4 phases and evaluated by applying the response model. RESULTS: In phase 1, efforts were made to block further transmission of the virus through preemptive testing of a religious group. In phase 2, efforts were concentrated on responding to mass infections in high-risk facilities. Phase 3 involved a transition from a high-intensity social distancing campaign to a citizen participation-based quarantine system. The evaluation using the response model revealed insufficient systematic preparation for a medical surge. In addition, an incorporated health-related management system and protection measures for responders were absent. Nevertheless, the city encouraged the participation of private hospitals and developed a severity classification system. Citizens also played active roles in the pandemic response by practicing social distancing. CONCLUSIONS: This study employed the response model to evaluate the early response in Daegu to the COVID-19 pandemic and revealed areas in need of improvement or maintenance. Based on the study results, creation of a systematic model is necessary to prepare for and respond to future public health emergencies like the COVID-19 pandemic.

Honeysuckle Berry (Lonicera caerulea L.) Inhibits Lipase Activity and Modulates the Gut Microbiota in High-Fat Diet-Fed Mice.

Honeysuckle berry (HB, Lonicera caerulea L.) is an oriental herbal medicine reported to have beneficial effects on metabolic disorders, such as obesity and non-alcoholic fatty liver disease. The fruit part of HB is rich in anthocyanin, a type of polyphenol. Most studies credit the antioxidant and anti-inflammatory properties of HB as the mechanisms of its effectiveness. This study investigated the inhibitory effects of HB on lipase using an in vitro assay and the modulatory effect of HB on gut microbiota in high-fat diet (HFD)-fed mice. HB inhibited pancreatic lipase activity with IC50 values of approximately 0.47 mg/mL. The fecal triglyceride (TG) levels were higher from the HFD of the HB-fed mice than they were for the control mice. Moreover, the fecal microbiota from the HFD of the HB-fed mice had relatively lower Firmicutes and higher Bacteroidetes than that from the HFD-only mice. These results suggest that HB modulates gut microbiota composition, which may contribute to body fat reduction. Hence, HB could present a useful agent for treating metabolic diseases through lower TG uptake and the regulation of gut microflora.

Ameliorative Effects of Lactobacillus plantarum HAC01 Lysate on 3T3-L1 Adipocyte Differentiation via AMPK Activation and MAPK Inhibition.

Lactobacillus plantarum HAC01 has been shown to effectively treat metabolic diseases. However, the precise pharmacological effects and molecular mechanisms of L. plantarum HAC01 remain unclear. In this study, we investigate the anti-adipogenic effects of L. plantarum HAC01 lysate and its associated mechanism of action. To induce lipid accumulation, 3T3-L1 cells were incubated in differentiation media with or without L. plantarum HAC01 lysate. Our results show that L. plantarum HAC01 lysate treatment not only reduced lipid accumulation during the differentiation of 3T3-L1 cells, but also decreased the expression of adipogenic and lipogenic genes involved in lipid metabolism in a dose-dependent manner. Additionally, L. plantarum HAC01 lysate inhibited CCAAT/enhancer-binding protein (C/EBP) beta within 4 h of differentiation induction and inhibited peroxisome proliferator-activated receptor gamma, C/EBP alpha, and sterol regulatory element-binding proteins within 2 d. Moreover, treatment with L. plantarum HAC01 lysate increased the phosphorylation of adenosine monophosphate-activated protein kinase, an important regulator of energy metabolism, and decreased the phosphorylation of mitogen-activated protein kinase. These results indicate that L. plantarum HAC01 lysate may have anti-adipogenic effects and support its potential as a useful agent for the treatment of obesity.

Association between Stroke and Abdominal Obesity in the Middle-Aged and Elderly Korean Population: KNHANES Data from 2011-2019.

Obesity and overweight status are primary risk factors for stroke. A relative small number of studies has analyzed the association of abdominal obesity, a crucial indicator for insulin resistance with stroke, compared to general obesity. We aimed to reveal 31,490 records from the Korea National Health and Nutrition Examination Survey (KNHANES). Logistic regression was used to identify the association of abdominal obesity with the risk of stroke. For the multivariate model, covariates were determined based on the cardio-cerebro vascular prediction models. In the sex-specific multivariate logistic regression analysis (including age, antihypertensive drug, diabetes, current smoking, and systolic blood pressure as confounders), the elevated waist circumference (WC) in women was significantly associated with the increased risk for stroke. In case of the categorized form of WC, we discerned the non-linear relationships between WC and the stroke status. The sex-specific associations between the abdominal obesity and stroke status were shown and their relationship pattern exhibited non-linear relationships.

Lactiplantibacillusplantarum ATG-K2 Exerts an Anti-Obesity Effect in High-Fat Diet-Induced Obese Mice by Modulating the Gut Microbiome.

Obesity is a major health problem. Compelling evidence supports the beneficial effects of probiotics on obesity. However, the anti-obesity effect of probiotics remains unknown. In this study, we investigated the anti-obesity effects and potential mechanisms of Lactiplantibacillus plantarum ATG-K2 using 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese mice. 3T3-L1 cells were incubated to determine the effect of lipid accumulation with lysate of L. plantarum ATG-K2. Mice were fed a normal fat diet or HFD with L. plantarum ATG-K2 and Orlistat for 8 weeks. L. plantarum ATG-K2 inhibited lipid accumulation in 3T3-L1 adipocytes, and reduced body weight gain, WAT weight, and adipocyte size in HFD-induced obese mice, concurrently with the downregulation of PPARγ, SREBP1c, and FAS and upregulation of PPARα, CTP1, UCP1, Prdm16, and ND5. Moreover, L. plantarum ATG-K2 decreased TG, T-CHO, leptin, and TNF-α levels in the serum, with corresponding gene expression levels in the intestine. L. plantarum ATG-K2 modulated the gut microbiome by increasing the abundance of the Lactobacillaceae family, which increased SCFA levels and branched SCFAs in the feces. L. plantarum ATG-K2 exhibited an anti-obesity effect and anti-hyperlipidemic effect in 3T3-L1 adipocytes and HFD-induced obese mice by alleviating the inflammatory response and regulating lipid metabolism, which may be influenced by modulation of the gut microbiome and its metabolites. Therefore, L. plantarum ATG-K2 can be a preventive and therapeutic agent for obesity.

Anti-Sarcopenic Obesity Effects of Lonicera caerulea Extract in High-Fat Diet-Fed Mice.

Sarcopenic obesity is a combination of sarcopenia and obesity. Although several herbal extracts showed improvement on sarcopenia and obesity, respectively, there are few studies on sarcopenic obesity. Lonicera caerulea (honeysuckle berry, HB) can ameliorate metabolic disorders including obesity. However, its effects on sarcopenic obesity have not been reported yet. Thus, the aim of this study was to investigate whether HB extract might have any beneficial effects on sarcopenic obesity in high-fat diet-induced mice. Forty-eight mice were classified into six groups and treated for eight weeks: (1) NC, normal diet control; (2) HC, high-fat diet control; (3) PC, high-fat diet with orlistat; (4) HB100, high-fat diet with HB extract at 100 mg/kg; (5) HB200, high-fat diet with HB extract at 200 mg/kg; and (6) HB400, high-fat diet with HB extract at 400 mg/kg. Body weight, fat accumulation, muscle mass, muscle strength, and mRNA expression of muscle atrophy were monitored. Compared with the HC group, HB administration showed anti-obesity properties. It reduced body weight gain and modulated serum biochemical parameters and tissue antioxidant enzymes. HB also increased muscle strength and muscle mass of hind legs. In addition, it decreased mRNA expression levels of Atrogin1 and MuRF1 as markers of muscle atrophy but increased PGC1α and SIRT1 as markers of muscle growth. These results suggest that HB might be effective in preventing sarcopenia associated with obesity.

Optimization of adipogenic differentiation conditions for canine adipose-derived stem cells.

BACKGROUND: Canine adipose-derived stem cells (cADSCs) exhibit various differentiation properties and are isolated from the canine subcutaneous fat. Although cADSCs are valuable as tools for research on adipogenic differentiation, studies focusing on adipogenic differentiation methods and the underlying mechanisms are still lacking. OBJECTIVES: In this study, we aimed to establish an optimal method for adipogenic differentiation conditions of cADSCs and evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) and estrogen receptor (ER) signaling in the adipogenic differentiation. METHODS: To induce adipogenic differentiation of cADSCs, 3 different adipogenic medium conditions, MDI, DRI, and MDRI, using 3-isobutyl-1-methylxanthine (M), dexamethasone (D), insulin (I), and rosiglitazone (R) were tested. RESULTS: MDRI, addition of PPARγ agonist rosiglitazone to MDI, was the most significantly facilitated cADSC into adipocyte. GW9662, an antagonist of PPARγ, significantly reduced adipogenic differentiation induced by rosiglitazone. Adipogenic differentiation was also stimulated when 17ß-estradiol was added to MDI and DRI, and this stimulation was inhibited by the ER antagonist ICI182,780. CONCLUSIONS: Taken together, our results suggest that PPARγ and ER signaling are related to the adipogenic differentiation of cADSCs. This study could provide basic information for future research on obesity or anti-obesity mechanisms in dogs.

Epidemiological characteristics of a COVID-19 outbreak caused by religious activities in Daegu, Korea.

OBJECTIVES: A coronavirus disease 2019 (COVID-19) outbreak triggered by religious activities occurred in Daegu, Korea in February 2020. This outbreak spread rapidly to the community through high-risk groups. This study describes the characteristics of COVID-19 cases based on S religious group membership and summarizes the Daegu municipal government's processes and responses to control the outbreak. METHODS: The epidemiological characteristics of confirmed cases were obtained through basic and in-depth epidemiological surveys. General characteristics, the proportion of asymptomatic cases, the case-fatality rate, and the time-to-event within each group were presented after stratifying confirmed cases according to S religious group membership. RESULTS: Overall, 7,008 COVID-19 cases were confirmed in Daegu from February 18, 2020 to June 30, 2020, and 61.5% (n= 4,309) were S religious group members. Compared with non-members, members had a higher proportion of female (p< 0.001) and younger age (p< 0.001), as well as lower disease prevalence. At the time of the investigation, 38.4% of cases in members were asymptomatic versus 23.7% of cases in non-members (p< 0.001). The case-fatality rate of non-members aged ≥ 60 years was significantly higher than that of members (p< 0.001). Compared with non-members, members had longer intervals from symptom onset to diagnosis (p< 0.001) and from diagnosis to admission (p< 0.001), and a shorter interval from admission to discharge (p< 0.001). CONCLUSIONS: The epidemiological features of S religious group members, including the proportion of asymptomatic cases, case-fatality rate, and time-to-event, differed from non-members. The Daegu authorities prevented further COVID-19 spread through immediate isolation and active screening tests of all S religious group members.

Role of PGC-1α in the Mitochondrial NAD+ Pool in Metabolic Diseases.

Mitochondria play vital roles, including ATP generation, regulation of cellular metabolism, and cell survival. Mitochondria contain the majority of cellular nicotinamide adenine dinucleotide (NAD+), which an essential cofactor that regulates metabolic function. A decrease in both mitochondria biogenesis and NAD+ is a characteristic of metabolic diseases, and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) orchestrates mitochondrial biogenesis and is involved in mitochondrial NAD+ pool. Here we discuss how PGC-1α is involved in the NAD+ synthesis pathway and metabolism, as well as the strategy for increasing the NAD+ pool in the metabolic disease state.

Lithium enhances exercise-induced glycogen breakdown and insulin-induced AKT activation to facilitate glucose uptake in rodent skeletal muscle.

The purpose of this study was to investigate the effect of lithium on glucose disposal in a high-fat diet-induced type 2 diabetes mellitus (T2DM) and streptozotocin-induced type 1 diabetes mellitus (T1DM) animal model along with low-volume exercise and low-dose insulin. Lithium decreased body weight, fasting plasma glucose, and insulin levels when to treat with low-volume exercise training; however, there were no adaptive responses like an increase in GLUT4 content and translocation factor levels. We discovered that lithium enhanced glucose uptake by acute low-volume exercise-induced glycogen breakdown, which was facilitated by the dephosphorylation of serine 473-AKT (Ser473-AKT) and serine 9-GSK3ß. In streptozotocin-induced T1DM mice, Li/low-dose insulin facilitates glucose uptake through increase the level of exocyst complex component 7 (Exoc7) and Ser473-AKT. Thus, lithium enhances acute exercise-induced glycogen breakdown and insulin-induced AKT activation and could serve as a candidate therapeutic target to regulate glucose level of DM patients.

New Simple 3-Dimensional Computed Tomogram Classification Leading to Successful Conservative Treatment in 51 Atlanto-Axial Rotatory Fixation Children.

OBJECTIVE: to present a new and easy classification of atlanto-axial rotatory fixation (AARF) and to investigate the efficiency of conservative treatment of AARF. BACKGROUND: Although there is a precise definition and diagnostic classification of AARF, there is still significant difficulty in measuring the atlas and axis angles because all of the atlas or axis cannot be seen in a certain 2-dimensional computed tomogram image. In addition, some recent case reports showed that long-term conservative treatment can reduce pediatric AARFs, even that are severe or chronic. METHODS: Fifty-one children with AARF were analyzed retrospectively with new 3-dimensional computed tomogram (3DCT)-based AARF classification; the mean age was 72.7 ± 35.2 months (19-139 months). In the new AARF classification, type 1 was defined as that when the C1C2 angle is not 0° on midline and type 2 as that when the C1C2 angle is 0° on the midline. RESULTS: All 7 children with AARF type 1 were treated successfully only with Halter tractions. Twenty among 44 children with type 2 did not show any difference in improvement compared with not-treated 24 children with type 2. CONCLUSION: The first new AARF classification based on 3DCT appears to be easy to use and even the most severe children with AARF may be managed only with conservative treatment such as long-term Halter traction.

Clinical Characteristics and Outcomes of COVID-19 Cohort Patients in Daegu Metropolitan City Outbreak in 2020.

BACKGROUND: A coronavirus disease 2019 (COVID-19) outbreak started in February 2020 and was controlled at the end of March 2020 in Daegu, the epicenter of the coronavirus outbreak in Korea. The aim of this study was to describe the clinical course and outcomes of patients with COVID-19 in Daegu. METHODS: In collaboration with Daegu Metropolitan City and Korean Center for Diseases Control, we conducted a retrospective, multicenter cohort study. Demographic, clinical, treatment, and laboratory data, including viral RNA detection, were obtained from the electronic medical records and cohort database and compared between survivors and non-survivors. We used univariate and multi-variable logistic regression methods and Cox regression model and performed Kaplan-Meier analysis to determine the risk factors associated with the 28-day mortality and release from isolation among the patients. RESULTS: In this study, 7,057 laboratory-confirmed patients with COVID-19 (total cohort) who had been diagnosed from February 18 to July 10, 2020 were included. Of the total cohort, 5,467 were asymptomatic to mild patients (77.4%) (asymptomatic 30.6% and mild 46.8%), 985 moderate (14.0%), 380 severe (5.4%), and 225 critical (3.2%). The mortality of the patients was 2.5% (179/7,057). The Cox regression hazard model for the patients with available clinical information (core cohort) (n = 2,254) showed the risk factors for 28-day mortality: age > 70 (hazard ratio [HR], 4.219, P = 0.002), need for O2 supply at admission (HR, 2.995; P = 0.001), fever (> 37.5°C) (HR, 2.808; P = 0.001), diabetes (HR, 2.119; P = 0.008), cancer (HR, 3.043; P = 0.011), dementia (HR, 5.252; P = 0.008), neurological disease (HR, 2.084; P = 0.039), heart failure (HR, 3.234; P = 0.012), and hypertension (HR, 2.160; P = 0.017). The median duration for release from isolation was 33 days (interquartile range, 24.0-46.0) in survivors. The Cox proportional hazard model for the long duration of isolation included severity, age > 70, and dementia. CONCLUSION: Overall, asymptomatic to mild patients were approximately 77% of the total cohort (asymptomatic, 30.6%). The case fatality rate was 2.5%. Risk factors, including older age, need for O2 supply, dementia, and neurological disorder at admission, could help clinicians to identify COVID-19 patients with poor prognosis at an early stage.