Nicotinamide riboside restores nicotinamide adenine dinucleotide levels and alleviates brain injury by inhibiting oxidative stress and neuroinflammation in a mouse model of intracerebral hemorrhage.

Hemorrhagic stroke is a global health problem owing to its high morbidity and mortality rates. Nicotinamide riboside is an important precursor of nicotinamide adenine dinucleotide characterized by a high bioavailability, safety profile, and robust effects on many cellular signaling processes. This study aimed to investigate the protective effects of nicotinamide riboside against collagenase-induced hemorrhagic stroke and its underlying mechanisms of action. An intracerebral hemorrhage model was constructed by stereotactically injecting collagenase into the right striatum of adult male Institute for Cancer Research mice. After 30 minutes, nicotinamide riboside was administered via the tail vein. The mice were sacrificed at different time points for assessments. Nicotinamide riboside reduced collagenase-induced hemorrhagic area, significantly reduced cerebral water content and histopathological damage, promoted neurological function recovery, and suppressed reactive oxygen species production and neuroinflammation. Nicotinamide riboside exerts neuroprotective effects against collagenase-induced intracerebral hemorrhage by inhibiting neuroinflammation and oxidative stress.

Identification and seasonal variation of specific particulate bound (halogenated) polycyclic aromatic hydrocarbons in air from different metal industrial parks in Northwest China.

During the process of industrial heating, a large amount of polycyclic aromatic hydrocarbons (PAHs) and their halogenated compounds (Cl/Br-PAHs) can be formed. However, there is still limited understanding of the chemicals from different metal smelting industrial parks. This study evaluated the seasonal variations, composition profiles, and source allocations of the atmospheric particulate-bound PAHs and Cl/Br-PAHs in different metal industrial parks in a typical industrial city in northwest China. The results showed that the main PAHs produced by metal smelting were low molecular weight isomers, and the concentrations of Cl-PAHs were lower compared to Br-PAHs. The main Br-PAHs were 1-Br-Pyr and 4-Br-Pyr, while 9-Cl-Fle, 1-Cl-Pyr, and 6-Cl-BaP were the dominated Cl-PAH isomers. No significant difference was found in the concentrations among the sites, whereas the levels of the target chemicals were higher during cold months compared to warm months. The main source of PAHs was coal combustion and gasoline vehicle emission during metal smelting, and that of Cl/Br-PAHs was also industrial coal burning. In addition to the primary source, the secondary chlorination of parent PAHs was also a significant source of Cl-PAHs in the production of high purity aluminum. This study suggests that Cl-PAHs and Br-PAHs may behave differently in the atmosphere.

Endometrial stem cells alleviate cisplatin-induced ferroptosis of granulosa cells by regulating Nrf2 expression.

BACKGROUND: Premature ovarian failure (POF) caused by cisplatin is a severe and intractable sequela for young women with cancer who received chemotherapy. Cisplatin causes the dysfunction of granulosa cells and mainly leads to but is not limited to its apoptosis and autophagy. Ferroptosis has been also reported to participate, while little is known about it. Our previous experiment has demonstrated that endometrial stem cells (EnSCs) can repair cisplatin-injured granulosa cells. However, it is still unclear whether EnSCs can play a repair role by acting on ferroptosis. METHODS: Western blotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were applied to detect the expression levels of ferroptosis-related genes. CCK-8 and 5-Ethynyl-2'-deoxyuridine (EdU) assays were used to evaluate cell viability. Transmission electron microscopy (TEM) was performed to detect ferroptosis in morphology. And the extent of ferroptosis was assessed by ROS, GPx, GSSG and MDA indicators. In vivo, ovarian morphology was presented by HE staining and the protein expression in ovarian tissue was detected by immunohistochemistry. RESULTS: Our results showed that ferroptosis could occur in cisplatin-injured granulosa cells. Ferroptosis inhibitor ferrostatin-1 (Fer-1) and EnSCs partly restored cell viability and mitigated the damage of cisplatin to granulosa cells by inhibiting ferroptosis. Moreover, the repair potential of EnSCs can be markedly blocked by ML385. CONCLUSION: Our study demonstrated that cisplatin could induce ferroptosis in granulosa cells, while EnSCs could inhibit ferroptosis and thus exert repair effects on the cisplatin-induced injury model both in vivo and in vitro. Meanwhile, Nrf2 was validated to participate in this regulatory process and played an essential role.

Exploring flatfeet morphology in children aged 6-12 years: relationships with body mass and body height through footprints and three-dimensional measurements.

The aim of the study was to determine the relationship between flatfoot morphology and body mass and height in children aged 6-12 years. A total of 6471 Chinese children (mean age 9.0 ± 1.9 years, 41% female) were assessed for foot morphometry, body height, and body mass index. Foot morphology, including foot length, width, girth, arch height, hallux valgus angle, and rearfoot valgus angle, was measured using a 3D laser scanner. Flatfoot evaluations were conducted using the Sztriter-Godunov index (KY) from footprints. All measurements were analyzed by age and sex using the mean values of the left and right sides. Comparisons were performed between flatfoot groups, between body mass index (BMI) groups, and between body height groups. The study revealed a significant decrease in the incidence of bipedal flatfoot with age (p < 0.001), whereas the prevalence of obesity remained consistent (p > 0.05). Bipedal flatfoot was associated with distinct morphological changes, including lower arches, reduced instep height, diminished ankle heights and a greater rearfoot valgus angle (p < 0.05). When comparing the BMI groups, overweight children had larger and thicker feet (p < 0.05), but no differences were found in arch height and ankle height (p > 0.05). When comparing the body height groups, short-statured children had a shorter feet girth, shorter arches, and shorter ankle height (p < 0.05), but no differences were found in the rearfoot valgus angle (p > 0.05). CONCLUSION: The main characteristics of flat feet include lower arches and instep heights and ankle heights but higher rearfoot valgus angles. In general, overweight children's feet do not have the common features of flat feet. In contrast, short children had similar features of flatfoot except for rearfoot valgus. Assessment of posture, such as rearfoot valgus, can be critical in identifying children with flat feet. WHAT IS KNOWN: • The morphology of children's feet is associated with body growth, but the relationship between flatfeet and body mass and height remains controversial. WHAT IS NEW: • Three-dimensional foot measurement shows that body mass is generally not associated with flatfeet, while short children have lower arches but no rearfoot valgus.

From genomic spectrum of NTRK genes to adverse effects of its inhibitors, a comprehensive genome-based and real-world pharmacovigilance analysis.

Introduction: The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has facilitated the development of precision oncology. Two first-generation NTRK inhibitors (larotrectinib and entrectinib) are currently approved for the treatment of patients with solid tumors harboring NTRK gene fusions. Nevertheless, comprehensive NTRK profiling at the pan-cancer genomic level and real-world studies pertaining to the adverse events of NTRK inhibitors are lacking. Methods: We characterize the genome of NTRK at the pan-cancer level through multi-omics databases such as The Cancer Genome Atlas (TCGA). Through the FDA Adverse Event Reporting System (FAERS) database, we collect reports of entrectinib and larotrectinib-induced adverse events and perform a pharmacovigilance analysis using various disproportionality methods. Results: NTRK1/2/3 expression is lower in most tumor tissues, while they have higher methylation levels. NTRK gene expression has prognostic value in some cancer types, such as breast invasive carcinoma (BRCA). The cancer type with highest NTRK alteration frequency is skin cutaneous melanoma (SKCM) (31.98%). Thyroid carcinoma (THCA) has the largest number of NTRK fusion cases, and the most common fusion pair is ETV6-NTRK3. Adverse drug events (ADEs) obtained from the FAERS database for larotrectinib and entrectinib are 524 and 563, respectively. At the System Organ Class (SOC) level, both drugs have positive signal value for "nervous system disorder". Other positive signals for entrectinib include "cardiac disorders", "metabolism and nutrition disorders", while for larotrectinib, it is "hepatobiliary disorders". The unexpected signals are also listed in detail. ADEs of the two NTRK inhibitors mainly occur in the first month. The median onset time of ADEs for entrectinib and larotrectinib was 16 days (interquartile range [IQR] 6-86.5) and 44 days ([IQR] 7-136), respectively. Conclusion: Our analysis provides a broad molecular view of the NTRK family. The real-world adverse drug event analysis of entrectinib and larotrectinib contributes to more refined medication management.

A pharmacovigilance study of etoposide in the FDA adverse event reporting system (FAERS) database, what does the real world say?

Introduction: Etoposide is a broad-spectrum antitumor drug that has been extensively studied in clinical trials. However, limited information is available regarding its real-world adverse reactions. Therefore, this study aimed to assess and evaluate etoposide-related adverse events in a real-world setting by using data mining method on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Through the analysis of 16,134,686 reports in the FAERS database, a total of 9,892 reports of etoposide-related adverse drug events (ADEs) were identified. To determine the significance of these ADEs, various disproportionality analysis algorithms were applied, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms. Results: As a result, 478 significant disproportionality preferred terms (PTs) that were identified by all four algorithms were retained. These PTs included commonly reported adverse events such as thrombocytopenia, leukopenia, anemia, stomatitis, and pneumonitis, which align with those documented in the drug's instructions and previous clinical trials. However, our analysis also uncovered unexpected and significant ADEs, including thrombotic microangiopathy, ototoxicity, second primary malignancy, nephropathy toxic, and ovarian failure. Furthermore, we examined the time-to-onset (TTO) of these ADEs using the Weibull distribution test and found that the median TTO for etoposide-associated ADEs was 10 days (interquartile range [IQR] 2-32 days). The majority of cases occurred within the first month (73.8%) after etoposide administration. Additionally, our analysis revealed specific high-risk signals for males, such as pneumonia and cardiac infarction, while females showed signals for drug resistance and ototoxicity. Discussion: These findings provide valuable insight into the occurrence of ADEs following etoposide initiation, which can potentially support clinical monitoring and risk identification efforts.

FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway.

Premature ovarian failure (POF) is a complicated disorder related to the apoptosis of granulosa cells. The incidence of chemotherapy-associated POF is rising dramatically owing to the increasing proportion of cancer in adolescents. According to previous studies, oxidative stress caused by chemotherapeutic agents plays an important role in the development of POF. However, the exact effects of nuclear factor-erythroid 2-related factor2 (NRF2), a pivotal anti-oxidative factor, are still unknown in chemotherapy-associated POF. Firstly, we manipulated NRF2 expressions on a genetic or pharmaceutical level in cisplatin-injured granulosa cell models. The results indicate that the increasing NRF2 in cisplatin-injured cells was just compensatory and not enough to resist the accumulated stress. Upregulation of NRF2 could protect granulosa cells against cisplatin via elevating autophagic level by using an autophagic activator (rapamycin) and inhibitor (chloroquine). Additionally, exogenous FGF2 exerted a protective role by increasing NRF2 expression and promoting its nuclear translocation. Meanwhile, the results in cisplatin-POF mice models were consistent with what was found in injured cells. In conclusion, our research proved that FGF2 rescued cisplatin-injured granulosa cells through the NRF2-autophagy pathway and might provide a possible alternative treatment choice by targeting NRF2 for POF patients who are intolerant or unsuitable to FGF2.

[Sensitivity Analysis of Ozone Formation Using Response Surface Methodology].

Identifying the nonlinear relationship between O3 and its precursors accurately plays an important role for the policy-making of O3 pollution control. In this study, the response surface methodology based on the box model simulation was used to quickly and efficiently quantify the O3 response to their precursors with the optimal experimental design. The results showed that CO had a positive contribution to ozone generation, whereas NOx and VOCs had a significant nonlinear relationship with O3. When the ratio of φ(VOCs) to[φ(NOx)-13.75] was greater than 4.17, the ozone formation regime was NOx-limited and became VOCs-limited when the ratio was less than 4.17. Olefin was the key VOCs' component to affect the formation of O3; when the radio of φ(olefin) to[φ(NOx)-15] was less than 1.10 and the value of the φ(olefin) was less than 35×10-9, olefin went far towards generating O3. Response surface methodology demonstrated that it can be well used to explore the influence of multiple factors and their interactions on O3 formation and provides a new approach for efficient O3 sensitivity analysis.

Updating and evaluating the NH3 gas-phase chemical mechanism of MOZART-4 in the WRF-Chem model.

The accuracy of determining atmospheric chemical mechanisms is a key factor in air pollution prediction, pollution-cause analysis and the development of control schemes based on air quality model simulations. However, the reaction of NH3 and OH to generate NH2 and its subsequent reactions are often ignored in the MOZART-4 chemical mechanism. To solve this problem, the gas-phase chemical mechanism of NH3 was updated in this study. Response surface methodology (RSM), integrated gas-phase reaction rate (IRR) diagnosis and process analysis (PA) were used to quantify the influence of the updated NH3 chemical mechanism on the O3 simulated concentration, the nonlinear response relationship of O3 and its precursors, the chemical reaction rate of O3 generation and the meteorological transport process. The results show that the updated NH3 chemical mechanism can reduce the error between the simulated and observed O3 concentrations and better simulate the O3 concentration. Compared with the Base scenario (original chemical mechanism simulated), the first-order term of NH3 in the Updated scenario (updated NH3 chemical mechanism simulated) in RSM passed the significance test (p < 0.05), indicating that NH3 emissions have an influence on the O3 simulation, and the effects of the updated NH3 chemical mechanism on NOx-VOC-O3 in different cities are different. In addition, the analysis of chemical reaction rate changes showed that NH3 can affect the generation of O3 by affecting the NOx concentration and NOx circulation with radicals of OH and HO2 in the Updated scenario, and the change of pollutant concentration in the atmosphere leads to the change of meteorological transmission, eventually leading to the reduction of O3 concentration in Beijing. In conclusion, this study highlights the importance of atmospheric chemistry for air quality models to model atmospheric pollutants and should attract more research focus.

Spontaneous rupture of an unscarred uterus during pregnancy: A rare but life-threatening emergency: Case series.

RATIONALE: In most cases, uterine rupture occurs during the third trimester of pregnancy or during labor. Even fewer reports have been published about the occurrence of this condition without a gynecologic history of any surgical procedure. Due to their scarcity and variable clinical presentation, early diagnosis of uterine rupture may be difficult, and if the diagnosis is not timely, the condition may be life-threatening. PATIENT CONCERNS: Herein, 3 cases of uterine rupture from a single institution are described. Three patients are at different gestational weeks and all have no history of uterine surgery. They came to the hospital due to acute abdominal pain, which is characterized by severe and persistent pain in the abdomen, with no apparent vaginal bleeding. DIAGNOSES: All 3 patients were diagnosed with uterine rupture during the operation. INTERVENTIONS: One patient underwent uterine repair surgery; while the other 2 underwent subtotal hysterectomy due to persistent bleeding and pathological examination after surgery confirmed placenta implantation. OUTCOMES: The patients recovered well after the operation, and no discomfort occurred in the follow-up. LESSONS: Acute abdominal pain during pregnancy can pose both diagnostic and therapeutic challenges. It is important to consider the possibility of uterine rupture, even in cases where there is no history of prior uterine surgery. The key to the treatment of uterine rupture is to shorten the diagnosis time as much as possible, this potential complication should be carefully monitored for and promptly addressed to ensure the best possible outcomes for both the mother and the developing fetus.

Effects of chemical boundary conditions on simulated O3 concentrations in China and their chemical mechanisms.

Chemical boundary conditions (BCs) are important inputs for regional chemical transport models. In this study, we use the brute-force method (BFM), process analysis (PA) and response surface model (RSM) to quantify the effects of BCs on simulated O3 concentrations in different regions of China by the weather research and forecasting with chemistry (WRF-Chem) model. We combine the model with an integrated gas-phase reaction rate (IRR) tool to further analyze the changes in the O3 chemical mechanisms. Our results show that the simulated O3 concentrations in western cities are significantly affected by the O3 in the BCs (BC-O3), which can increase the maximum simulated O3 concentration, such as in Lanzhou (36.6 µg/m3, 26.3 %), Wuhai (30.1 µg/m3, 25.5 %) and Urumqi (50.7 µg/m3, 41.2 %). In contrast, O3 generation in the eastern region is dominated by emissions. Subsequently, we compare the reaction rate changes in O3 generation and consumption under the effects of BC-O3 in the western city of Urumqi and the eastern city of Beijing. The results show that in Beijing, the O3 concentration and the related chemical reaction rates undergo little change, while in Urumqi, the concentration and reaction rates have significant differences. The BC-O3 significantly accelerates the O3 photochemical reaction process in Urumqi, resulting in increased O3 generation and consumption reaction rates; additionally, there may be a chemical reaction pathway for the formation of O3: BC-O3 + NO → NO2 + hv → O + O2 → O3. BC-O3 transmission is the main pathway of changes in the simulated O3 concentration in the study area, and the chemical reactions between BC-O3 and local pollutants are primarily characterized by O3 consumption. In conclusion, the study shows the importance of BCs for regional model simulation while providing supporting information for O3 formation in model studies.

Chemical reactivity of volatile organic compounds and their effects on ozone formation in a petrochemical industrial area of Lanzhou, Western China.

Measurements of ozone (O3) and its precursors were performed in the summer of 2019 in Lanzhou, a petrochemical industrial city, to better understand the reactivity of volatile organic compounds (VOCs) and their effects on O3 production. During the campaign, the daily maximum 8-hour average (MDA8) O3, NO2, and total VOC (TVOC) concentrations reached 72.2 ± 19.9 ppb, 24.9 ± 10.8 ppb, and 50.8 ± 46.1 ppb, respectively. Alkanes, alkenes, halocarbons, aromatics, and alkynes contributed 45.3%, 24.0%, 16.5%, 10.0%, and 4.2% to TVOCs, respectively. The OH reactivity and relative incremental reactivity (RIR) of VOCs at different times were calculated. The results indicated that alkenes played a predominant role, accounting for an average of 68.5% of the initial VOC reactivity. Compared to other regions, alkenes are relatively more important for O3 formation in the petrochemical industry area of Lanzhou, while aromatics are relatively less important. Generally, O3 formation occurred in a VOC-limited regime in the morning and in a transitional regime in the afternoon. The response surface methodology (RSM) combined with a chemical box model was applied to obtain relationships between O3 and its precursors and determine the most effective way to reduce the O3 concentration. Reduction in the non-alkene concentration slightly affected the O3 concentration. In contrast, the effect of nitrogen oxides (NOx) was closely related to the alkene concentration, and NOx concentration reduction could lead to an increase in the O3 concentration when alkenes were abated to less than 80% of the present concentration. To mitigate O3 pollution near the petrochemical industrial area of Lanzhou, reducing the alkene concentration, especially the C4 alkene concentration (1,3-butadiene, cis-2-butene, and trans-2-butene), was the fastest and most effective control strategy. The results of this study serve as a reference for O3 pollution control in petrochemical industrial areas.

RRx-001 Exerts Neuroprotection Against LPS-Induced Microglia Activation and Neuroinflammation Through Disturbing the TLR4 Pathway.

Neuroinflammation plays an important role in the pathogenesis of many central nervous system diseases. Here, we investigated the effect of an anti-cancer compound RRx-001 on neuroinflammation and its possible new applications. BV2 cells and primary microglia cells were used to evaluate the role of RRx-001 in LPS-induced microglial activation and inflammatory response in vitro. And, we found that the increase in the synthesis and release of cytokines and the up-regulation of pro-inflammatory factors in LPS-treated microglial cells were significantly reduced by RRx-001 pretreatment. As the most classical inflammatory pathways, NF-κB and MAPK signaling pathways were activated by LPS, but were inhibited by RRx-001. Transcription of NLRP3 was also reduced by RRx-001. In addition, LPS induced oxidative stress by increasing the expression of Nox mediated by transcription factors NF-κB and AP-1, while RRx-001 pretreatment ameliorated Nox-mediated oxidative stress. LPS-induced activation of TAK1, an upstream regulator of NF-κB and MAPK pathways, was significantly inhibited by RRx-001 pretreatment, whereas recruitment of MyD88 to TLR4 was not affected by RRx-001. LPS-primed BV2 condition medium induced injury of primary neurons, and this effect was inhibited by RRx-001. Furthermore, we established a neuroinflammatory mouse model by stereotactic injection of LPS into the substantia nigra pars compacta (SNpc), and RRx-001 dose-dependently reduced LPS-induced microglial activation and loss of TH + neurons in the midbrain. In conclusion, the current study found that RRx-001 suppressed microglia activation and neuroinflammation through targeting TAK1, and may be a candidate for the treatment of neuroinflammation-related brain diseases.

Mechanical response of surface wettability of Janus porous membrane and its application in oil-water separation.

Smart surfaces with switchable wettability are widely studied for environmental application. Although a large number of stimulation routes provide broad prospects for the development of smart surfaces, achieving high sensitivity, fast response and recovery, simple operation, security and good stability is still challenging. Herein, a Janus membrane via electrospinning, chemical bath deposition and heat treatment is constructed. By using the hydrophilic ZIF-L nanosheet to functionalize the hydrophobic thermoplastic polyurethane (TPU) substrate, a smart surface utilizes the ZIF-L crack induced by strain in the hydrophilic layer to control surface wettability is obtained. In the range of 0%-100% strain, the wettability of the smart surface presents an obvious change with stretching, and water contact angle of the surface shows a monotonic increase with a maximum tuning range from 47° to 114°. Due to local fusion of the TPU microfibers and good binding between the ZIF-L layer and the TPU substrate after heat treatment, the prepared Janus membrane exhibits consistent and symmetrical hydrophilic-hydrophobic-hydrophilic transition curves in 50 stretching-releasing cycles. Thanks to the porous and asymmetric architecture, the membrane shows good oil-water separation performance, and the separation flux increases with the increase of strain, while the separation efficiency is always higher than 98%. Because of the excellent structural stability, the robust membrane with 100% strain maintains its oil-water separation property for 50 stretching-releasing cycles. This study provides a new perspective for the development of smart material with stimuli responsive surface for oily wastewater purification.

NADPH is superior to NADH or edaravone in ameliorating metabolic disturbance and brain injury in ischemic stroke.

Our previous studies confirm that exogenous reduced nicotinamide adenine dinucleotide phosphate (NADPH) exerts a neuroprotective effect in animal models of ischemic stroke, and its primary mechanism is related to anti-oxidative stress and improved energy metabolism. However, it is unknown whether nicotinamide adenine dinucleotide (NADH) also plays a neuroprotective role and whether NADPH is superior to NADH against ischemic stroke? In this study we compared the efficacy of NADH, NADPH, and edaravone in ameliorating brain injury and metabolic stress in ischemic stroke. Transient middle cerebral artery occlusion/reperfusion (t-MCAO/R) mouse model and in vitro oxygen glucose deprivation/reoxygenation (OGD/R) model were established. The mice were intravenously administered the optimal dose of NADPH (7.5 mg/kg), NADH (22.5 mg/kg), or edaravone (3 mg/kg) immediately after reperfusion. We showed that the overall efficacy of NADPH in ameliorating ischemic injury was superior to NADH and edaravone. NADPH had a longer therapeutic time window (within 5 h) after reperfusion than NADH and edaravone (within 2 h) for ischemic stroke. In addition, NADPH and edaravone were better in alleviating the brain atrophy, while NADH and NADPH were better in increasing the long-term survival rate. NADPH showed stronger antioxidant effects than NADH and edaravone; but NADH was the best in terms of maintaining energy metabolism. Taken together, this study demonstrates that NADPH exerts better neuroprotective effects against ischemic stroke than NADH and edaravone.

Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors.

Coenzyme I (nicotinamide adenine dinucleotide, NAD+/NADH) and coenzyme II (nicotinamide adenine dinucleotide phosphate, NADP+/NADPH) are involved in various biological processes in mammalian cells. NAD+ is synthesised through the de novo and salvage pathways, whereas coenzyme II cannot be synthesised de novo. NAD+ is a precursor of coenzyme II. Although NAD+ is synthesised in sufficient amounts under normal conditions, shortage in its supply due to over consumption and its decreased synthesis has been observed with increasing age and under certain disease conditions. Several studies have proved that in a wide range of tissues, such as liver, skin, muscle, pancreas, and fat, the level of NAD+ decreases with age. However, in the brain tissue, the level of NADH gradually increases and that of NAD+ decreases in aged people. The ratio of NAD+/NADH indicates the cellular redox state. A decrease in this ratio affects the cellular anaerobic glycolysis and oxidative phosphorylation functions, which reduces the ability of cells to produce ATP. Therefore, increasing the exogenous NAD+ supply under certain disease conditions or in elderly people may be beneficial. Precursors of NAD+ have been extensively explored and have been reported to effectively increase NAD+ levels and possess a broad range of functions. In this review article, we discuss the pharmacokinetics and pharmacodynamics of NAD+ precursors.

Epidemiological investigation of Helicobacter pylori infection in elderly people in Beijing.

BACKGROUND: The Helicobacter pylori (H. pylori) infection rate in China is approximately 50%. H. pylori is a pathogenic factor of peptic ulcer and chronic gastritis. In addition, H. pylori infection may also be associated with a variety of cardiovascular diseases in elderly people, such as arteriosclerosis, coronary heart disease, and cerebral infarction, having deleterious effect on their health. With the aging of the population, the disease characteristics of the elderly population have been increasingly valued by the whole society. We conducted an epidemiological survey of H. pylori infection among elderly people in Beijing to provide a basis for health management of H. pylori infection. AIM: To understand the epidemiological characteristics of H. pylori infection in elderly people in Beijing. METHODS: A total of 1090 elderly people aged more than 60 years from different parts of Beijing (urban and rural areas) were selected using the random cluster sampling method. Structured questionnaires were completed during home visits and the 13C-urea breath test was conducted for H. pylori detection. RESULTS: The prevalence of H. pylori infection was 46.5% (507/1090). The infection rate in men was 51.8%, which was significantly higher than that in women (42.5%; P < 0.05). The H. pylori infection rate in illiterate people was significantly higher than that in literate persons (53.5% vs 44.8%, P < 0.05). The total infection rate of H. pylori gradually increased with age and the difference was statistically significant (P < 0.01). The H. pylori infection rate in smokers was significantly higher than that in non-smokers and those who had quit smoking (P < 0.05). CONCLUSION: The prevalence of H. pylori infection among elderly people is 46.5% and the infection rate gradually increases with age. Sex, education level, age, and smoking were determined to be H. pylori infection risk factors. The relationship of H. pylori infection with region, occupation, drinking, and diet structure needs to be further studied.

Characterization of PAF-AH Ib1 in NOD mice: PAF-AH may not be a candidate gene of the diabetes susceptibility Idd4.1 locus.

We recently mapped Idd4 to a 5.2 cM interval on chromosome 11 with two subloci, Idd4.1 and Idd4.2, in nonobese diabetic (NOD) mice. Based on the localization of platelet-activating factor acetylhydrolase Ib1 (PAF-AHIb1) and the decreased activity of PAF-AH in type 1 diabetes (T1D) patients, we hypothesized that PAF-AHIb1 in Idd4.1 is a candidate gene. The PAF-AHIb1 gene in NOD mice was cloned and sequenced, and its expression and function were studied. No polymorphisms were detected in PAF-AHIb1 cDNA between NOD and B6 mice. The expression of PAF-AH Ib1 at the mRNA and protein levels was found to be similar in different tissues between NOD and B6 mice. PAF-AH activity does not differ in the pancreatic islets or spleen between NOD and B6 mice. Our findings suggest that PAF-AH Ib1 may not be a diabetes-susceptibility gene in the Idd4.1 sublocus.