MITOCHONDRIAL ANTIVIRAL PATHWAYS CONTROL ANTI-HIV RESPONSES AND ISCHEMIC STROKE OUTCOMES VIA THE RIG-1 SIGNALING AND INNATE IMMUNITY MECHANISMS.

Occludin (ocln) is one of the main regulatory cells of the blood-brain barrier (BBB). Ocln silencing resulted in alterations of the gene expression signatures of a variety of genes of the innate immunity system, including IFN-stimulated genes (ISGs) and the antiviral retinoic acid-inducible gene-1 (RIG-1) signaling pathway, which functions as a regulator of the cytoplasmic sensors upstream of the mitochondrial antiviral signaling protein (MAVS). Indeed, we observed dysfunctional mitochondrial bioenergetics, dynamics, and autophagy in our system. Alterations of mitochondrial bioenergetics and innate immune protection translated into worsened ischemic stroke outcomes in EcoHIV-infected ocln deficient mice. Overall, these results allow for a better understanding of the molecular mechanisms of viral infection in the brain and describe a previously unrecognized role of ocln as a key factor in the control of innate immune responses and mitochondrial dynamics, which affect cerebral vascular diseases such as ischemic stroke.

Accelerated Conversion of Polysulfides for Ultra Long-Cycle of Li-S Battery at High-Rate over Cooperative Cathode Electrocatalyst of Ni0.261Co0.739S2/N-Doped CNTs.

Despite the very high theoretical energy density, Li-S batteries still need to fundamentally overcome the sluggish redox kinetics of lithium polysulfides (LiPSs) and low sulfur utilization that limit the practical applications. Here, highly active and stable cathode, nitrogen-doped porous carbon nanotubes (NPCTs) decorated with NixCo1-xS2 nanocrystals are systematically synthesized as multi-functional electrocatalytic materials. The nitrogen-doped carbon matrix can contribute to the adsorption of LiPSs on heteroatom active sites with buffering space. Also, both experimental and computation-based theoretical analyses validate the electrocatalytic principles of co-operational facilitated redox reaction dominated by covalent-site-dependent mechanism; the favorable adsorption-interaction and electrocatalytic conversion of LiPSs take place subsequently by weakening sulfur-bond strength on the catalytic NiOh 2+-S-CoOh 2+ backbones via octahedral TM-S (TM = Ni, Co) covalency-relationship, demonstrating that fine tuning of CoOh 2+ sites by NiOh 2+ substitution effectively modulates the binding energies of LiPSs on the NixCo1-xS2@NPCTs surface. Noteworthy, the Ni0.261Co0.739S2@NPCTs catalyst shows great cyclic stability with a capacity of up to 511 mAh g-1 and only 0.055% decay per cycle at 5.0 C during 1000 cycles together with a high areal capacity of 2.20 mAh cm-2 under 4.61 mg cm-2 sulfur loading even after 200 cycles at 0.2 C. This strategy highlights a new perspective for achieving high-energy-density Li-S batteries.

RNA Profiling of Brain Microvessels Reveals Altered Morphology and Signaling in a Mouse Model of Alzheimer's Disease.

Disruptions in pericyte and endothelial cell expression can compromise the integrity of the blood-brain barrier (BBB), leading to neurovascular dysfunction and the development of neurological disorders. However, the study of microvessel RNAs has been limited to tissue homogenates, with spatial visualization only available for protein targets. We introduce an innovative microvessel isolation technique that is RNA-friendly for the purpose of coupling with RNAscope analysis. RNA-friendly microvessel isolation combined with RNAscope analysis enables the visualization of cell-specific RNA within the spatial and histological context of the BBB. Using this approach, we have gained valuable insights into the structural and functional differences associated with the microvessels of 5XFAD mice, a mouse model of Alzheimer's disease (AD). RNAscope analysis revealed a decrease in pericytes from microvessels isolated from 5XFAD mice in comparison to wild-type mice. Additionally, the microvessels of 5XFAD mice exhibited an increase in TYROBP mRNA expression. These findings significantly advance our understanding of neurovascular interactions and hold great promise for guiding the development of targeted therapeutic interventions. This innovative approach enables visualization of cell RNA while preserving the spatial and histological context of the BBB, shedding light on the mechanisms underlying neurovascular unit communication.

AKT signaling modulates latent viral reservoir viability in HIV-1-infected blood-brain barrier pericytes.

Despite antiretroviral therapy (ART), chronic forms of HIV-associated neurocognitive disorders (HAND) affect an estimated 50% of individuals living with HIV, greatly impacting their quality of life. The prevailing theory of HAND progression posits that chronic inflammation arising from the activation of latent viral reservoirs leads to progressive damage in the central nervous system (CNS). Recent evidence indicates that blood-brain barrier (BBB) pericytes are capable of active HIV-1 infection; however, their latent infection has not been defined. Given their location and function, BBB pericytes are poised to be a key viral reservoir in the development of HAND. We present the first transcriptional analysis of uninfected, active, and latent human BBB pericytes, revealing distinct transcriptional phenotypes. In addition, we demonstrate that latent infection of BBB pericytes relies on AKT signaling for reservoir survival. These findings provide insight into the state of reservoir maintenance in the CNS during HIV-1 infection and provide novel targets for reservoir clearance.

Gender Difference of the Association between Energy Intake Expenditure Balance and Depression among Korean Adults: A Cross-Sectional Study from the 2014, 2016, and 2018 Korea National Health and Nutrition Examination Survey.

BACKGROUND: Diet and physical activity are key factors related to depressive mood. Previous studies have demonstrated the effects of diet and physical activity on depression. However, the effect of energy intake-expenditure balance (EIEB) on mental health has not been fully evaluated. This study aimed to analyze the association between EIEB and depression. METHODS: A total of 13,460 participants (5,660 men and 7,800 women) aged ≥19 years were obtained from the 2014, 2016, and 2018 Korea National Health and Nutrition Examination Survey (KNHANES). EIEB was defined as the difference between the daily energy intake and energy expenditure. Energy intake was calculated and provided by the KNHANES using a 24-hour recall survey. Energy expenditure was estimated as the sum of basal metabolic rate and physical activity. Logistic regression analyses were used to investigate the association between sex-specific quartile groups (Q1-Q4) of EIEB and depression after adjusting for socioeconomic status, body mass index, lifestyle factors, and underlying diseases. RESULTS: Women in Q3 of EIEB (211-669 kcal) had a significantly lower risk of depression (odd ratio [OR], 0.78; 95% confidence interval [CI], 0.67-0.92) than those in Q1 of EIEB (<-167 kcal). The adjusted ORs of depression were 0.87 (95% CI, 0.75-1.02) in Q2 and 0.86 (95% CI, 0.74-1.01) in Q4, with P for trend=0.030. There were no significant associations between the EIEB quartile groups and depression in men after adjusting for potential confounders (P for trend=0.564). CONCLUSION: Our results suggested that the EIEB is negatively associated with depression in Korean women.

Protective Effect of Novel Lactobacillus plantarum KC3 Isolated from Fermented Kimchi on Gut and Respiratory Disorders.

Probiotics have been shown to possess anti-inflammatory effects in the gut by directly reducing the production of pro-inflammatory cytokines and by secreting anti-inflammatory molecules. However, their systemic anti-inflammatory effects have not been thoroughly investigated. In this study, we aimed to develop probiotics that have efficacy in both intestinal and lung inflammation. Lactobacillus plantarum KC3 (KC3), which was isolated from kimchi, was selected as a pre-candidate based on its inhibitory effects on the production of pro-inflammatory cytokines in vitro. To further validate the effectiveness of KC3, we used ear edema, DSS-induced colitis, and ambient particulate-matter-induced lung inflammation models. First, KC3 exhibited direct anti-inflammatory effects on intestinal cells with the inhibition of IL-1ß and TNF-α production. Additionally, KC3 treatment alleviated ear edema and DSS-induced colic inflammation, improving colon length and increasing the number of regulatory T cells. Beyond its local intestinal anti-inflammatory activity, KC3 inhibited pro-inflammatory cytokines in the bronchoalveolar fluid and prevented neutrophil infiltration in the lungs. These results suggest that KC3 could be a potential functional ingredient with respiratory protective effects against air-pollutant-derived inflammation, as well as for the treatment of local gut disorders.

Clinical Outcomes of Resectional Roux-en-Y Gastric Bypass, Compared to Sleeve Gastrectomy for Severe Obesity.

PURPOSE: Resectional Roux-en-Y gastric bypass (RRYGB) is considered an alternative bariatric surgery in countries with a high incidence of stomach cancer because there is no excluded stomach after RRYGB. This study aimed to evaluate the efficacy and safety of RRYGB. MATERIALS AND METHODS: This study included patients who underwent RRYGB and sleeve gastrectomy (SG) between 2011 and 2021. Surgical complications and metabolic and nutritional profiles were compared between the patients preoperatively and at 1, 6, and 12 months after surgery. RESULTS: Twenty and seventy-six patients underwent RRYGB and SG, respectively; 7 in the SG group were lost to follow-up within 1 year. Surgical complications and baseline characteristics were comparable between two groups, except for diabetes (90.0% vs. 44.7%, p < 0.001). The decrease of HbA1c levels and incidence of reflux esophagitis were lower in the RRYGB group compared to that of SG at 1-year postoperative (-3.0% vs. -1.8%, p = 0.014; 0% vs. 26.7%, p = 0.027). The percentage of total weight loss at 1- year postoperative and incidence of dumping syndrome were comparable between the two groups. The RRYGB group had significantly lower total cholesterol level (161.9 mg/dl vs. 196.4 mg/dl, p < 0.001), but higher incidence of vitamin B12 deficiency (30.0% vs. 3.6%, p = 0.003) at 1 year postoperative compared to those of the SG group. CONCLUSIONS: The RRYGB group had better postoperative outcomes for diabetes and dyslipidemia without increasing surgical complications compared to that of the SG group. Thus, RRYGB can be considered a safe and effective alternative in areas where gastric cancer is prevalent.

Exploitation of a novel adjuvant for polymyxin B against multidrug-resistant Acinetobacter baumannii.

BACKGROUND: Although polymyxin has been used as a last-resort antibiotic against resistant bacteria, its use is restricted due to nephrotoxicity and neurotoxicity. While the present antibiotic resistance issue compels clinicians to reconsider polymyxin use in severe illness cases, polymyxin-resistant microorganisms exert an effect. OBJECTIVES: To address the issue of antibiotic resistance, the cycle of developing new antibiotics to counteract emerging resistance must be discontinued. Here we tried to develop novel therapies that do not rely on direct antimicrobial activity and thus do not promote antibiotic resistance. METHODS: By a high-throughout screening system based on bacterial respiration, chemical compounds accelerating the antimicrobial effects of polymyxin B were screened. In vitro and in vivo tests were performed to validate adjuvanticity. In addition, membrane depolarization and total transcriptome analysis were used to determine molecular mechanisms. RESULTS: PA108, a newly discovered chemical compound, was used to eradicate polymyxin-resistant A. baumannii and three other species in the presence of polymyxin B at concentrations less than the MIC. Since this molecule lacks self-bactericidal action, we hypothesized that PA108 acts as an antibiotic adjuvant, enhancing the antimicrobial activity of polymyxin B against resistant bacteria. At working concentrations, no toxicity was observed in cell lines or mice, although co-treatment with PA108 and polymyxin B increased survival of infected mouse and decreased bacterial loads in organs. CONCLUSIONS: Boosting antibiotic efficiency through the use of antibiotic adjuvants holds significant promise for tackling the rise in bacterial antibiotic resistance.

How to Change the Reaction Chemistry on Nonprecious Metal Oxide Nanostructure Materials for Electrocatalytic Oxidation of Biomass-Derived Glycerol to Renewable Chemicals.

Au and Pt are well-known catalysts for electrocatalytic oxidation of biomass-derived glycerol. Although some nonprecious-metal-based materials to replace the costly Au and Pt are used for this reaction, the fundamental question of how the nonprecious catalysts affect the reaction chemistry and mechanism compared to Au and Pt catalysts is still unanswered. In this work, both experimental and computational methods are used to understand how and why the reaction performance and chemistry for the electrocatalytic glycerol oxidation reaction (EGOR) change with electrochemically-synthesized CuCo-oxide, Cu-oxide, and Co-oxide catalysts compared to conventional Au and Pt catalysts. The Au and Pt catalysts generate major glyceric acid and glycolic acid products from the EGOR. Interestingly, the prepared Cu-based oxides produce glycolic acid and formic acid with high selectivity of about 90.0%. This different reaction chemistry is related to the enhanced ability of CC bond cleavage on the Cu-based oxide materials. The density functional theory calculations demonstrate that the formic acids are mainly formed on the Cu-based oxide surfaces rather than in the process of glycolic acid formation in the free energy diagram. This study provides critical scientific insights into developing future nonprecious-based materials for electrochemical biomass conversions.

Changes in predicted lean body mass, appendicular skeletal muscle mass, and body fat mass and cardiovascular disease.

BACKGROUND: Little is known about the association of changes in two body components, muscle and fat mass, with the risk of cardiovascular disease (CVD) among young adults. We investigated the association of changes in predicted lean body mass index (LBMI), appendicular skeletal muscle mass index (ASMI), and body fat mass index (BFMI) with the development of CVD among young adults. METHODS: This nationwide, population-based cohort study included 3 727 738 young adults [2 406 046 (64.5%) men and 1 321 692 (35.5%) women] aged 20-39 years without a previous history of CVD who underwent two health screening examinations during 2009-2010 and 2011-2012. Using validated and robust prediction equations, we calculated the changes in predicted LBMI, ASMI, and BFMI from the first to the second examinations. RESULTS: The mean (SD) age was 32.2 (4.9) years, and 2 406 046 (64.5%) of the participants were men. A total of 23 344 CVD events were detected during 22 257 632 person-years of follow-up. Each 1 kg/m2 increase in predicted LBMI and ASMI change was associated with a reduced risk of CVD among men [adjusted hazard ratio (aHR): 0.86, 95% confidence interval (CI) 0.82-0.91; aHR: 0.76, 95% CI 0.69-0.82, respectively] and women (aHR: 0.77, 95% CI 0.63-0.95; aHR: 0.75, 95% CI 0.59-0.96). Each 1 kg/m2 increase in predicted BFMI change was associated with an increased risk of CVD among men (aHR: 1.16, 95% CI 1.10-1.22) and women (aHR: 1.32, 95% CI 1.06-1.65). In both sexes, decreases in predicted LBMI and ASMI were associated with greater CVD risk, and decreased predicted BFMI was associated with a reduced CVD risk. Those who maintained their BMI between -1 and +1 kg/m2 also had a decreased risk of CVD per 1 kg/m2 increase in predicted LBMI and ASMI change among men (aHR: 0.86, 95% CI 0.80-0.92; aHR: 0.85, 95% CI 0.76-0.95) and women (aHR: 0.62, 95% CI 0.47-0.83; aHR: 0.59, 95% CI 0.44-0.80) and had a greater risk of CVD per 1 kg/m2 increase in predicted BFMI change among men (aHR: 1.17, 95% CI 1.10-1.25) and women (aHR: 1.64, 95% CI 1.20-2.23). Regardless of changes in weight, such as from normal to obese or vice versa, these results were consistent. CONCLUSIONS: Among young adults, increased predicted muscle mass or decreased predicted fat mass were associated with a reduced risk of development of CVD. Decreased predicted muscle mass or increased predicted fat mass were associated with an elevated risk of development of CVD.

Body composition and osteoporotic fracture using anthropometric prediction equations to assess muscle and fat masses.

BACKGROUND: Obesity is protective of bone health; however, abdominal obesity is associated with a higher fracture risk. Little is known about whether body composition protects or adversely affects osteoporotic fractures because of practical issues regarding assessment tools. This study aimed to evaluate the association of predicted body composition with fracture risk to determine the distinctive and differing effects of muscle or fat mass on bone health outcomes in the general population. METHODS: This population-based, longitudinal cohort study used 2009-2010 Korean National Health Insurance Service data and follow-up data from 1 January 2011 to 31 December 2013, to determine the incidence of osteoporotic fracture (total, spine, and non-spine) defined using the International Classification of Diseases, Tenth Revision codes. The study participants were aged ≥50 years (men, 158 426; women, 131 587). The predicted lean body mass index (pLBMI), appendicular skeletal muscle index (pASMI), and body fat mass index (pBFMI) were used to assess body composition, using anthropometric prediction equations. RESULTS: Over a 3 year follow-up, we identified 2350 and 6175 fractures in men and women, respectively. The mean age of the participants was 60.2 ± 8.3 and 60.7 ± 8.4 years in men and women, respectively. In a multivariable-adjusted Cox proportional hazards regression model, increasing pLBMI or pASMI was significantly associated with a decreased risk of total fractures in men and women. When comparing individuals in the lowest pLBMI and pASMI (reference groups), men with the highest pLBMI and pASMI had adjusted hazard ratios of 0.63 [95% confidence interval (CI) 0.47-0.83] and 0.62 (95% CI 0.47-0.82), and women with the highest pLBMI and pASMI had adjusted hazard ratios of 0.72 (95% CI 0.60-0.85) and 0.71 (95% CI 0.60-0.85), respectively, for total fractures. The pBFMI had no significant association with total fractures in men or women. Regarding sex-specific or site-specific differences, the protective effects of the pLBMI and pASMI on fractures were greater in men and reduced the risk of spinal fractures. An increased pBFMI was associated with an increased risk of spinal fractures in women. CONCLUSIONS: An increased pLBMI or pASMI was significantly associated with decreased total osteoporotic fracture risk; however, the pBFMI showed no statistically significant association. Muscle mass was more important than fat mass in preventing future osteoporotic fractures based on anthropometric prediction equations.

Synergistic Impairment of the Neurovascular Unit by HIV-1 Infection and Methamphetamine Use: Implications for HIV-1-Associated Neurocognitive Disorders.

The neurovascular units (NVU) are the minimal functional units of the blood-brain barrier (BBB), composed of endothelial cells, pericytes, astrocytes, microglia, neurons, and the basement membrane. The BBB serves as an important interface for immune communication between the brain and peripheral circulation. Disruption of the NVU by the human immunodeficiency virus-1 (HIV-1) induces dysfunction of the BBB and triggers inflammatory responses, which can lead to the development of neurocognitive impairments collectively known as HIV-1-associated neurocognitive disorders (HAND). Methamphetamine (METH) use disorder is a frequent comorbidity among individuals infected with HIV-1. METH use may be associated not only with rapid HIV-1 disease progression but also with accelerated onset and increased severity of HAND. However, the molecular mechanisms of METH-induced neuronal injury and cognitive impairment in the context of HIV-1 infection are poorly understood. In this review, we summarize recent progress in the signaling pathways mediating synergistic impairment of the BBB and neuronal injury induced by METH and HIV-1, potentially accelerating the onset or severity of HAND in HIV-1-positive METH abusers. We also discuss potential therapies to limit neuroinflammation and NVU damage in HIV-1-infected METH abusers.

Brain-Accumulating Nanoparticles for Assisting Astrocytes to Reduce Human Immunodeficiency Virus and Drug Abuse-Induced Neuroinflammation and Oxidative Stress.

Human neurotropic immunodeficiency virus (HIV) ingress into the brain and its subsequent replication after infection results in viral reservoirs in the brain. The infected cells include microglia, perivascular macrophages, and astrocytes. HIV-associated neurocognitive disorders (HAND) affect glial cells by activating microglia and macrophages through neuroinflammation, as well as astrocytes through mitochondrial dysfunctions and the onset of oxidative stress, impairing the ability of these cells to engage in neuroprotection. Furthermore, the risk of neuroinflammation associated with HAND is magnified by recreational drug use in HIV-positive individuals. Most of the therapeutic options for HIV cannot be used to tackle the virus in the brain and treat HAND due to the inability of currently available combination antiretroviral therapies (ARTs) and neuroprotectants to cross the blood-brain barrier, even if the barrier is partially compromised by infection. Here, we report a strategy to deliver an optimized antiretroviral therapy combined with antioxidant and anti-inflammatory neuroprotectants using biodegradable brain-targeted polymeric nanoparticles to reduce the burden caused by viral reservoirs in the brain and tackle the oxidative stress and inflammation in astrocytes and microglia. Through in vitro coculture studies in human microglia and astrocytes as well as an in vivo efficacy study in an EcoHIV-infected, methamphetamine-exposed animal model, we established a nanoparticle-based therapeutic strategy with the ability to treat HIV infection in the central nervous system in conditions simulating drug use while providing enhanced protection to astrocytes, microglia, and neurons.

Prediction of 8-year risk of cardiovascular diseases in Korean adult population.

Although many prediction models for cardiovascular diseases (CVDs) have been developed and validated for Western populations, the development of CVD prediction models for Asians has been slow. Our cohort study retrospectively analyzed the incidence of CVD that occurred between January 1, 2009, and December 31, 2016, in all Koreans who underwent national health screening. This dataset included 21,581,796 adults between the ages of 40 and 79 years (10,412,947 men, 11,168,849 women) without CVD at baseline. The primary outcome, CVD, was defined as the development of any of the following: acute coronary syndrome, cerebral infarction, and cerebral hemorrhage, as defined with health insurance claims data. The prediction model was constructed by Cox proportional hazard regression and validated with tenfold cross-validation. The performance of the models was evaluated through Harrell's C-index and Brier score. The discrimination of the models was assessed by the area under the receiver operating characteristic curve (AUROC). Our model showed an AUROC of 0.762 in men and 0.811 in women. The Brier score of our model was 0.018 in men and 0.010 in women, which was better than the pooled cohort equation (PCE). Our novel model performed better than the FRS and PCE for Koreans.

Short- and Long-Term Exposure to Particulate Matter and Pulse Wave Velocity.

BACKGROUND: In hemodialysis patients, brachial-ankle pulse wave velocity (baPWV) levels are affected by particulate matter with an aerodynamic diameter of 10 µm or less (PM10). We conducted this study to determine whether there is an association between short- and long-term PM10 exposure and baPWV in apparently healthy adults aged 40 years and older. METHODS: A total of 1,628 subjects who underwent health examinations between 2006 and 2009 were included in the study. On the basis of the day of medical screening, the 1-3-day and 365-day moving averages of PM10 concentrations were used to evaluate the association between short- and long-term exposure to PM10 and high baPWV (≥the third quartile of baPWV, 1,534 cm/s) using logistic regression models. Additional subgroup analyses were conducted according to age, sex, obesity (body mass index ≥25.0 kg/m2), and comorbidities such as metabolic syndrome. RESULTS: No statistically significant associations were identified between short-term and long-term exposure to PM10 and baPWV in any of the subjects and subgroups. A 10-µg/m3 increase in the 2-day moving average of PM10 exposure was marginally associated with high baPWV in non-obese subjects (odds ratio, 1.059; P=0.058). This association in non-obese subjects was significantly different from that in obese subjects (P=0.038). CONCLUSION: This study did not show statistically significant associations between short-term and long-term exposure to PM10 and baPWV in apparently healthy subjects. With short-term exposure to PM10, non-obese subjects showed a marginally unfavorable association with baPWV. Further studies are necessary to validate and elucidate the mechanism underlying the effect of PM10 on baPWV.

Body weight variability and cancer incidence in men aged 40 years and older-Korean National Insurance Service Cohort.

Repeated weight fluctuation has been proposed as a potential risk factor for increasing morbidity and mortality including cancer. We aimed to investigate the association between body weight variability (BWV) and all cancer and site-specific cancer incidence and the impact of smoking on these associations. A total of 1,759,848 cancer-free male subjects who had their weight measured at least 5 times from the National Health Insurance Service-Health Screening Cohort from 2002 to 2011 were included and followed up until 2015. BWV was defined as the average absolute difference between successive values (ASV). The risk of cancer and site-specific cancer from BWV was identified using Cox proportional hazards regression analysis using hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders including weight, and stratified analysis was also conducted according to smoking status. During the 7,015,413 person-years of follow-up, 11,494 patients (0.65%) developed new-onset cancers. BWV was associated with a higher risk of all cancers after adjustment for confounders. The highest BWV quintile group compared to the lowest had greater risks of all cancers and site-specific cancers including lung, liver, and prostate cancer (HR 1.22, 95% CI 1.15-1.30; HR 1.22, 95% CI 1.07-1.39; HR 1.46, 95% CI 1.19-1.81; HR 1.36, 95% CI 1.15-1.62, in all cancers, lung, liver and prostate cancer, respectively). Due to small number of cancer occurrence, the risk of kidney cancer was increased, but statistically insignificant (HR 1.38, 95% CI 0.91-2.10). Similar results were observed in noncurrent smokers. However, in current smokers, the risks of all cancers and only prostate cancer were significantly increased in the highest BWV quintile group (HR 1.19, 95% CI 1.09-1.31; HR 1.51, 95% CI 1.08-2.11). The risk of kidney cancer also increased in this group, although the finding was not statistically significant (HR 1.77, 95% CI 0.87-3.63) This study suggested BWV is an independent risk factor for cancer in men, especially in lung, liver, and prostate cancer, but evidence was weaker in kidney cancer. This association remained significant only in prostate cancer in current smokers.

Methamphetamine Enhances HIV-Induced Aberrant Proliferation of Neural Progenitor Cells via the FOXO3-Mediated Mechanism.

Maintaining an intact pool of neural progenitor cells (NPCs) is crucial for generating new and functionally active neurons. Methamphetamine (METH) can exacerbate the HIV-induced deficit of adult neurogenesis; however, potential mechanisms of this influence are still poorly understood. In the present study, we present evidence that chronic exposure to METH combined with brain infection by EcoHIV results in enhanced proliferation of NPCs in the subventricular zone (SVZ) in mice. This effect was long-lasting as it was preserved ex vivo in NPCs isolated from the exposed mice over several passages in the absence of additional treatments. Increased proliferation in response to METH plus HIV was associated with dysregulation of cyclin B1 and cyclin D. Transcriptomic studies indicated that 27 out of the top 30 differentially expressed genes in response to METH plus EcoHIV were targets of the forkhead box O transcriptional factor (FOXO) and primarily FOXO3. Additional ex vivo studies and in vitro experiments using human NPCs exposed to METH and infected with HIV revealed upregulation of the CXCL12-CXCR4 axis, leading to activation of downstream pAkt and pErk, the pathways that can phosphorylate FOXO3 and force its exports from the nuclei into the cytoplasm. Indeed, nuclear expulsion of FOXO3 was demonstrated both in mice exposed to METH and infected with EcoHIV and in cell cultures of human NPCs. These results provide novel information that exposure to METH combined with HIV infection can induce aberrant proliferation of SVZ-derived NPCs and identifies CXCL12-CXCR4-Akt-1-mediated phosphorylation of FOXO3 as the mechanism responsible for this effect.

Risk of coronary heart disease among cancer survivors with different prediagnosis body mass index.

Association between body mass index (BMI) and coronary heart disease (CHD) in cancer survivors is not clearly established. This study analyzed the prediagnosis BMI-CHD association by examining 13,500 cancer survivors identified from the National Health Insurance Service-Health Screening Cohort from January 1, 2004 to December 31, 2009 including the patients who were free of cardiovascular disease at enrollment. The Cox proportional hazards model (adjusted for socioeconomic, health behavior, health status, and medical characteristics) was used for calculating hazard ratios (HR) and 95% confidence intervals (95% CI) for CHD in each prediagnosis BMI category among cancer survivors. Compared to cancer survivors with a prediagnosis BMI between 18.5 and 22.9 kg/m2, those with a prediagnosis BMI of 23.0-24.9 kg/m2 and ≥ 25.0 kg/m2 had significantly higher CHD risk (HR = 1.51; 95% CI: 1.13-2.01 and HR = 1.38; 95% CI: 1.04-1.84, respectively). Cancer survivors with a low prediagnosis BMI (< 18.5 kg/m2) also had significantly higher CHD risk (HR = 1.97; 95% CI: 1.20-3.24) compared to those with a BMI of 18.5-22.9 kg/m2. Similar associations were found after stratifying analyses based on first cancer site and sociodemographic and medical characteristic subgroups. Our study suggests that prediagnosis underweight among patients with cancer is a predictor of CHD risk.