A Highly Sensitive and Selective Fluorescent Sensor for Folic Acid Detection Based on D-penicillamine Stabilized Ag/Cu Alloy Nanoclusters.

In this work, a highly sensitive and selective method for detecting folic acid (FA) was developed using D-penicillamine (DPA) stabilized Ag/Cu alloy nanoclusters (DPA@Ag/Cu NCs). The yellow emission of DPA@Ag/Cu NCs was found to be quenched upon the addition of FA to the system. The fluorescence intensity quenching value demonstrated a linear relationship with FA concentrations ranging from 0.01 to 1200 µM, with a limit of detection (LOD) of 5.3 nM. Furthermore, the detection mechanism was investigated through various characterization analyses, including high resolution transmission electron microscopy, fluorescence spectra, ultraviolet-visible absorption spectra, and fluorescence lifetime. The results indicated that the fluorescence quenching induced by FA was a result of electron transfer from FA to the ligands of DPA@Ag/Cu NCs. The selectivity of the FA sensor was also evaluated, showing that common amino acids and inorganic ions had minimal impact on the detection of FA. Moreover, the standard addition method was successfully applied to detect FA in human serum, chewable tablets and FA tablets with promising results. The use of DPA@Ag/Cu NCs demonstrates significant potential for detecting FA in complex biological samples.

Joint-tissue integrative analysis identifies high-risk genes for Parkinson's disease.

The loss of dopaminergic neurons in the substantia nigra and the abnormal accumulation of synuclein proteins and neurotransmitters in Lewy bodies constitute the primary symptoms of Parkinson's disease (PD). Besides environmental factors, scholars are in the early stages of comprehending the genetic factors involved in the pathogenic mechanism of PD. Although genome-wide association studies (GWAS) have unveiled numerous genetic variants associated with PD, precisely pinpointing the causal variants remains challenging due to strong linkage disequilibrium (LD) among them. Addressing this issue, expression quantitative trait locus (eQTL) cohorts were employed in a transcriptome-wide association study (TWAS) to infer the genetic correlation between gene expression and a particular trait. Utilizing the TWAS theory alongside the enhanced Joint-Tissue Imputation (JTI) technique and Mendelian Randomization (MR) framework (MR-JTI), we identified a total of 159 PD-associated genes by amalgamating LD score, GTEx eQTL data, and GWAS summary statistic data from a substantial cohort. Subsequently, Fisher's exact test was conducted on these PD-associated genes using 5,152 differentially expressed genes sourced from 12 PD-related datasets. Ultimately, 29 highly credible PD-associated genes, including CTX1B, SCNA, and ARSA, were uncovered. Furthermore, GO and KEGG enrichment analyses indicated that these genes primarily function in tissue synthesis, regulation of neuron projection development, vesicle organization and transportation, and lysosomal impact. The potential PD-associated genes identified in this study not only offer fresh insights into the disease's pathophysiology but also suggest potential biomarkers for early disease detection.

The optimal cut-off value of five-time chair stand test for assessing sarcopenia among Chinese community-dwelling older adults.

BACKGROUND: The five-time chair stand test (5CST) as an indicator of muscle strength and physical function is the first step in assessing sarcopenia. We aimed to determine the optimal cut-off value of the 5CST for assessing older adults with sarcopenia in the Chinese community. METHODS: We used a stratified cluster random sampling method to recruit older adults from Chinese communities. The handgrip strength was assessed using an electronic handgrip dynamometer. The 5CST and gait speed were assessed by the trained researchers. The bioimpedance analysis device was used to evaluate the skeletal muscle index. We used the Asian Working Group for Sarcopenia diagnosis criteria as the gold standard. According to the receiver operating characteristic curve, we determine the optimal cut-off value using the Youden index. RESULTS: A total of 1027 participants were included in this analysis, including 337 men and 690 women with an average age of 70.35 ± 7.24 years. The prevalence of sarcopenia in total participants was 24.9%. The optimal cut-off value of 5CST in the total population was 10.9 s. Stratified by age and gender, for the older adults aged 60-69 years, the optimal cut-off values were 9.2 s in men and 10.8 s in women; for the older adults aged 70-79 years, cut-off values were 10.2 s in men and 10.9 s in women; and for the older adults over 80 years, cut-off values were 14.0 s in men and 11.5 s in women (all P < 0.001). The areas under the curve of 5CST were 0.632 in men and 0.650 in women (both P < 0.001). Using the newly defined cut-off values, the prevalence of sarcopenia increased significantly (P < 0.001). CONCLUSIONS: We determined the optimal cut-off value of the 5CST for assessing older adults with sarcopenia in the Chinese community, and this cut-off can significantly improve the detection rate of sarcopenia. The cut-off determined in our study will help community workers detect more people with sarcopenia and benefit from early intervention and management of sarcopenia in practice.

Visible-Light Photoredox-Catalyzed Three-Component Reaction of Carbazoles with Alkenes and S-(Difluoromethyl)sulfonium Salt: A Practical Approach to Access Difluoroalkyl-Functionalized Carbazoles.

A mild and elegant multicomponent protocol for construction of CF2H-containing carbazoles was accomplished by visible-light photoredox catalysis with formation of two new C-C bonds in a single step to deliver a wide variety of structurally diverse difluoroalkylated carbazoles in moderate to good yields, featuring mild reaction conditions, synthetic simplicity, broad substrates, and good functional group tolerance.

Heel bone mineral density and various oral diseases: a bidirectional Mendelian randomization.

INTRODUCTION: Observational studies demonstrated that the relationship between bone mineral density and oral diseases is mixed. To access the association between heel bone mineral density and various oral diseases, we conducted the Mendelian randomization analysis to explore the association. MATERIALS AND METHODS: Two-sample bidirectional Mendelian analysis was used to explore the relationship between heel bone mineral density and various oral diseases. The inverse-variance weighted (IVW) was used as the primary effect estimate, and various methods were applied to test the reliability and stability of the results, namely MR-Egger, weighted median, simple mode, and weighted mode. RESULTS: This study showed that there was a negative relationship between heel BMD and periodontitis when heel BMD was used as an exposure factor and periodontitis as an outcome factor (IVW OR = 0.85; 95% CI, 0.75-0.95; p = 0.005). Bidirectional Mendelian randomization showed that there was no statistically significant association between periodontitis and heel bone mineral density when chronic periodontitis was the exposure factor (p > 0.05). And there was no significant relationship between heel bone mineral density and other oral diseases (dental caries, diseases of pulp and periapical tissues, impacted teeth, cleft lip, and cleft palate, oral and oropharyngeal cancer) (p > 0.05). CONCLUSION: This study showed that there was a negative relationship between heel bone density and periodontitis, and the decrease in heel bone density could promote the occurrence of periodontitis. In addition, there was no statistically significant relationship between heel bone density and other oral diseases.

Visible-light photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamides with S-(difluoromethyl)sulfonium salt.

A facile and highly efficient visible-light photoredox-catalyzed protocol for aryldifluoromethylation of acrylamides was developed using S-(difluoromethyl)sulfonium salt as the difluoromethyl source. With this method, pharmaceutically interesting CF2H-containing oxindoles were readily accessed from N-arylacrylamides, and this method featured mild reaction conditions, a broad scope of substrates, good tolerance of functional groups, and good to excellent yields. Control experiments revealed that this protocol proceeded through a difluoromethylation/cyclization cascade process.

Mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation for ferroptosis after spinal cord injury.

Spinal cord injury is characterized by different aetiologies, complex pathogenesis, and diverse pathological changes. Current treatments are not ideal, and prognosis is generally poor. After spinal cord injury, neurons die due to various forms of cell death. Among them, ferroptosis causes dysfunction after spinal cord injury, and no existing traditional treatments have been indicated to block its occurrence. Meanwhile, emerging therapies using mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation therapy are promising for reversing spinal cord neuronal ferroptosis after spinal cord injury. However, no definitive studies have demonstrated the effectiveness of these approaches. This review summarizes the existing research on the mechanisms of ferroptosis; ferroptosis after spinal cord injury; treatment of spinal cord injury with mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation; and treatment of ferroptosis using mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation. Inhibiting ferroptosis can promote the reversal of neurological dysfunction after spinal cord injury. In addition, mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation can reverse adverse outcomes of spinal cord injury and regulate ferroptosis-related factors. Thus, it can be inferred that mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation have the potential to inhibit ferroptosis after spinal cord injury. This review serves as a reference for future research to confirm these conclusions.

Facile Entry to Pharmaceutically Important 3-Difluoromethyl-quinoxalin-2-ones Enabled by Visible-Light-Driven Difluoromethylation of Quinoxalin-2-ones.

CF2H moiety has a significant potential utility in drug design and discovery, and the incorporation of CF2H into biologically active molecules represents an important and efficient strategy for seeking lead compounds and drug candidates. On the other hand, quinoxalin-2-one is of great interest to pharmaceutical chemists as a common skeleton frequently occurring in plenty of natural products and bioactive compounds. Herein, we reported a practical and efficient protocol for the synthesis of 3-CF2H-quinoxalin-2-ones. Thus, in the presence of 3 mol% of photocatalyst and S-(difluoromethyl)sulfonium salt as difluoromethyl radical sources, a wide range of quinoxalin-2-ones readily underwent a visible-light redox-catalyzed difluoromethylation reaction, to deliver structurally diverse 3-difluoromethyl-quinoxalin-2-ones. We believe that this would facilitate increasing chances and possibilities for seeking potential lead compounds and drug candidates and further boost the development of fluorine-containing pharmaceuticals.

Can dietary patterns prevent cognitive impairment and reduce Alzheimer's disease risk: Exploring the underlying mechanisms of effects.

Alzheimer's disease (AD) is one of the fastest growing cognitive decline-related neurological diseases. To date, effective curative strategies have remained elusive. A growing body of evidence indicates that dietary patterns have significant effects on cognitive function and the risk of developing AD. Previous studies on the association between diet and AD risk have mainly focused on individual food components and specific nutrients, and the mechanisms responsible for the beneficial effects of dietary patterns on AD are not well understood. This article provides a comprehensive overview of the effects of dietary patterns, including the Mediterranean diet (MedDiet), dietary approaches to stop hypertension (DASH) diet, Mediterranean-DASH diet intervention for neurological delay (MIND), ketogenic diet, caloric restriction, intermittent fasting, methionine restriction, and low-protein and high-carbohydrate diet, on cognitive impairment and summarizes the underlying mechanisms by which dietary patterns attenuate cognitive impairment, especially highlighting the modulation of dietary patterns on cognitive impairment through gut microbiota. Furthermore, considering the variability in individual metabolic responses to dietary intake, we put forward a framework to develop personalized dietary patterns for people with cognitive disorders or AD based on individual gut microbiome compositions.

Thermal strain and fluid balance during a 72-km military route march in a field setting.

Introduction: A physiological profiling study was conducted to evaluate thermal strain as well as fluid and electrolyte balances on heat-acclimatised men performing a 72-km route march in a field setting. Methods: 38 male soldiers (age range 18-23 years) participated in the study, as part of a cohort that marched for 72 km, with loads for about 26 hours. Core temperature and heart rate sensors were used for the duration of the march. Fluid and food intake and output were monitored for the duration of the march. Blood samples were taken one day before the march (pre-march), immediately after the march (Post 1) and on the 15th day after the march to ascertain recovery (Post 2) to assess fluid and electrolyte profiles. Results: Mean core temperature was within safe limits, ranging from 37.1 to 38.1°C throughout the march. There was an overall decrease in serum sodium levels, a decline in serum sodium concentration in 28 participants and three instances of hyponatraemia (serum sodium concentration <135 mmol/L). Conclusion: Our study found low thermal strain heat-acclimatised individuals during a 72-km route march. However, there was an overall decrease in serum sodium levels, even when the participants were allowed to drink ad libitum. Challenges of exercise-associated hyponatraemia during prolonged activities remain to be addressed.

Difluoromethyl Radical Triggered Tandem Reaction of N-Allyl Amides to Difluoromethylated ß-Amino Alcohols by Photoredox Catalysis.

An elegant tandem reaction process for transferring N-allyl amide into CF2H-ß-amino alcohol is described. This approach proceeded smoothly under visible light irradiation in the presence of a 3 mol % Ir complex, exhibiting a broad substrate scope and functional group tolerance, and a variety of CF2H-ß-amino alcohols were readily accessed in good to excellent yields under mild conditions. The reliable mechanistic studies revealed that sequential difluoromethyl radical addition/carbocation trap/rearrangement is involved.

[Construction and Anti-tumor Effect Evaluation of a Dual-Responsive Hyaluronic Acid Carbon Quantum Dot-Gelatin Nano-Drug Delivery System].

OBJECTIVE: To construct a pH and matrix metalloproteinase (MMP) dual-responsive nano drug delivery system with adjustable particle size so as to synergistically enhance the retention and penetration of chemotherapeutic drugs in tumor tissues and improve tumor treatment effect. METHODS: Hyaluronic acid (HA) carbon quantum dots (CD) coupled with gelatin nanoparticle (GNP) were constructed, and were connected with doxorubicin (DOX), a chemotherapeutic drug, through pH-sensitive imine to produce GNP@HA-CD-DOX nanoparticles. The changes of particle size, drug release behavior, hemocompatibility, cell uptake and deep penetration of tumor spheroids, in vivo tumor targeting and therapeutic effect were analyzed. RESULTS: GNP@HA-CD-DOX nanoparticles had a particle size of (162.93±2.55) nm, which could be degraded to release HA-CD-DOX with a particle size of about 40 nm under the treatment of MMP. The drug loading of DOX was (4.94±0.22)%. DOX was released in the tumor microenvironment and lysosomes in response to the low pH. No obvious hemolysis was observed in GNP@HA-CD-DOX. GNP@HA-CD-DOX showed a reduction in particle size after co-incubation with MMP-2. The MMP-sensitive GNP@HA-CD-DOX had significantly improved cell uptake and better deep penetration in tumor spheres. GNP@HA-CD-DOX displayed better distribution in tumor and anti-tumor ability in tumor-bearing mice compared with the small particle size HA-CD-DOX group. In addition, it has better safety. CONCLUSION: The pH and MMP dual-sensitive nano-tech drug delivery system with adjustable particle sizes synergistically enhances the retention and deep penetration of drugs in tumors as well as the anti-tumor effect, suggesting new approaches to tumor treatment.

Update: Efficacy of Military Fluid Intake Guidance.

BACKGROUND: Fluid intake during military training is prescribed based on the interactions among work rates, environmental conditions, and uniform configurations. The efficacy of this guidance has not been empirically assessed in over a decade. To determine the acceptability of the fluid intake guidance, sweat losses were measured in a variety of conditions with modern uniform/body armor configurations and were then compared to prescribed fluid intakes for each condition (workload, environment, clothing). METHODS: Whole body sweat losses of 324 Soldiers and 14 model simulations were measured under a variety of work intensities ((Watts) easy, moderate, hard), work durations (2-25 h), environmental conditions (White-Black flag), and uniform configurations (including Army Combat Uniform and body armor). Whole body sweat losses were then calculated relative to 4 h drinking guidance and in accordance with TB MED 507 recommended work/rest ratios. The differences between the prescribed fluid intake and sweat loss were calculated and expressed as a percent loss or gain of body weight. Values within a threshold of ±2% body water flux (BWF) were deemed an acceptable conservative starting point for performance and health concerns. FINDINGS: Values within ±2% BWF numbered 309/338; 25 of 338 observations exceeded the +2% BWF while 4 of 338 observations exceeded the -2% BWF. When total fluid restriction was simulated, all experienced body weight loss with 151 of 338 observations exceeding the -2% BWF. DISCUSSION: When calculated using actual measured sweating rates from the laboratory and model simulations, current fluid intake guidance appears to predict with 91.4% accuracy the volume of fluid required to maintain a proper euhydrated state (±2%) during 4 h of exercise. Simulations of total fluid restriction support the necessity for fluid intake guidance so that the Warfighter's performance does not degrade. It is recommended that the current military fluid intake guidance focuses on methods for accurately tracking fluid intakes.

Nonlinear mixed effects modelling for the analysis of longitudinal body core temperature data in healthy volunteers.

Many longitudinal studies have collected serial body core temperature (T c) data to understand thermal work strain of workers under various environmental and operational heat stress environments. This provides the opportunity for the development of mathematical models to analyse and forecast temporal T c changes across populations of subjects. Such models can reduce the need for invasive methods that continuously measure T c. This current work sought to develop a nonlinear mixed effects modelling framework to delineate the dynamic changes of T c and its association with a set of covariates of interest (e.g. heart rate, chest skin temperature), and the structure of the variability of T c in various longitudinal studies. Data to train and evaluate the model were derived from two laboratory investigations involving male soldiers who participated in either a 12 (N = 18) or 15 km (N = 16) foot march with varied clothing, load and heat acclimatisation status. Model qualification was conducted using nonparametric bootstrap and cross validation procedures. For cross validation, the trajectory of a new subject's T c was simulated via Bayesian maximum a posteriori estimation when using only the baseline T c or using the baseline T c as well as measured T c at the end of every work (march) phase. The final model described T c versus time profiles using a parametric function with its main parameters modelled as a sigmoid hyperbolic function of the load and/or chest skin temperature. Overall, T c predictions corresponded well with the measured data (root mean square deviation: 0.16 °C), and compared favourably with those provided by two recently published Kalman filter models.

Highly selective, sensitive and fluorescent sensing of dimeric G-quadruplexes by a dimeric berberine.

This paper describes the highly selective, sensitive and topology-specific fluorescent sensing of dimeric G-quadruplexes by a polyether-tethered dimeric berberine 1. Compound 1 displays high selectivity for dimeric G-quadruplexes over monomeric ones, and can be lit up by dimeric G-quadruplexes, in particular by the one linked with one TTA subunit. In addition, it shows no effect on the topology or thermal stability of the G-quadruplexes.

An artificial blood vessel implanted three-dimensional microsystem for modeling transvascular migration of tumor cells.

Reproducing a tumor microenvironment consisting of blood vessels and tumor cells for modeling tumor invasion in vitro is particularly challenging. Here, we report an artificial blood vessel implanted 3D microfluidic system for reproducing transvascular migration of tumor cells. The transparent, porous and elastic artificial blood vessels are obtained by constructing polysaccharide cellulose-based microtubes using a chitosan sacrificial template, and possess excellent cytocompatibility, permeability, and mechanical characteristics. The artificial blood vessels are then fully implanted into the collagen matrix to reconstruct the 3D microsystem for modeling transvascular migration of tumor cells. Well-defined simulated vascular lumens were obtained by proliferation of the human umbilical vein endothelial cells (HUVECs) lining the artificial blood vessels, which enables us to reproduce structures and functions of blood vessels and replicate various hemodynamic parameters. Based on this model, the adhesion and transvascular migration of tumor cells across the artificial blood vessel have been well reproduced.

Body Mass Changes Across a Variety of Running Race Distances in the Tropics.

BACKGROUND: Current literature evaluating body mass (BM) changes across a variety of running race distances is limited. The primary objective of this study was to profile the range of BM changes across race distances. The secondary objective was to evaluate the prevalence of exercise-associated hyponatremia (EAH) in runners admitted to the on-site medical tent following participation of race events of different distances. METHODS: A total of 1934 runners across seven footrace categories (10-, 21-, 25-, 42-, 50-, 84-, and 100-km) were included in the study. One thousand eight hundred eighty-seven runners had their BM measured before and after each race. Blood sodium concentrations were measured from the remaining 47 symptomatic runners admitted to the on-site medical tents and did not complete the race. RESULTS: In terms of hydration status, 106 (6 %) were overhydrated, 1377 (73 %) were euhydrated, and 404 (21 %) were dehydrated. All race distances exhibited similar percentage of overhydrated runners (5 % in 10 km, 3 % in 21 km, 5 % in 25 km, 6 % in 42 km, 8 % in 50 km, 7 % in 84 km, and 6 % in 100 km). Forty-seven runners were admitted to the medical tents. Eight (17 %) were diagnosed with EAH (4 from 42 km, 2 from 84 km, 2 from 100 km), 38 (81 %) were normonatremic, and 1 (2 %) was hypernatremic. The % ΔBM across all races ranged from -8.0 to 4.1 % with a greater decrement noted in the 42-, 50-, 84-, and 100-km categories. CONCLUSIONS: Approximately 3-8 % runners had increased post-race BM, suggesting overhydration regardless of race distance. Symptomatic EAH was seen at race distances at or above 42 km, where BM changes demonstrated the widest range of values.

Effects of a carbohydrate-electrolyte solution on cognitive performance following exercise-induced hyperthermia in humans.

BACKGROUND: There is limited information on the effects of sports drinks on cognitive function after exercise in the heat. We aimed to investigate the effects of ingesting a commercially available carbohydrate-electrolyte (CHO) solution on cognitive performance following exercise-induced hyperthermia. METHODS: Twelve participants completed three practices of cognitive tests, one full familiarisation and two experimental trials in an environmental chamber (dry bulb temperature: 30.2 ± 0.3°C, relative humidity: 70 ± 3%). The experimental trials consisted of five cognitive tests (symbol digit matching, search and memory, digit span, choice reaction time and psychomotor vigilance test) performed before and after a 75-min run on a treadmill at 70% VO2 max. One ml/kg body mass of a 6.8% CHO solution or placebo was consumed at the start, every 15 min during exercise and between cognitive tests after exercise. Core temperature, heart rate, blood glucose concentrations, subjective ratings and cognitive performance were assessed (symbol digit matching, search and memory, digit span, choice reaction time and psychomotor vigilance). RESULTS: Participants were hyperthermic at the end of the run (placebo: 39.5 ± 0.4°C, CHO: 39.6 ± 0.5°C; Mean ± SD; p = 0.37). The change in blood glucose was higher with CHO ingestion (1.6, 0.7 to 4.5 mmol/L) (median, range) than with placebo ingestion (0.9, -0.1 to 4.7 mmol/L; p < 0.05). CHO ingestion reduced the maximum span of digits memorized, in contrast to an increase in maximum span with placebo ingestion (p < 0.05). CHO solution had no effect on other cognitive tests (p > 0.05). CONCLUSIONS: These results suggest that CHO solution ingestion may impair short-term memory following exertional heat stress.

Chemotherapy mediates intestinal injury via p53/p53 upregulated modulator of apoptosis (PUMA) signaling pathway.

OBJECTIVE: The aim of this study was to investigate the potential mechanism and signaling pathway involved in chemotherapy-induced intestinal mucosal injury (CIMI), which is a common physiopathological problem in patients with cancer. METHODS: For the in vivo experiment, mice received intraperitoneal injection of 5-fluorouracil (5-FU) at a dose of 75 mg/kg/day for 1, 3 or 5 days. Villus height and crypt depth of the small intestine, cell apoptosis and proliferation were then examined to determine the extent of CIMI. The expressions of Akt, p53, PUMA and p21 were evaluated both in vivo in mice models and in vitro in the IEC-6 and HCT116 cell lines. RESULTS: After 5-FU therapy both the intestinal villus height (275.93 µm vs 164.52 µm, P < 0.001) and crypt depth (64.13 µm vs 42.48 µm, P < 0.001) were decreased. The apoptotic index was greatly increased from 0.32% to 15.84% (P < 0.001) and proliferation was suppressed (63.58% vs 39.15%, P < 0.001). Additionally, p53 expression was significantly increased in the intestinal crypt along with the expressions of PUMA and p21. Western blot showed that the administration of 5-FU induced p53/PUMA-mediated apoptosis and upregulated p21 expression to suppress cell proliferation. CONCLUSION: Chemotherapy might mediate intestinal injury via p53/PUMA-mediated apoptotic signaling and the suppression of proliferation in response to p21.

Tumor necrosis factor-α mediates JNK activation response to intestinal ischemia-reperfusion injury.

AIM: To investigate whether tumor necrosis factor-α (TNF-α) mediates ischemia-reperfusion (I/R)-induced intestinal mucosal injury through c-Jun N-terminal kinase (JNK) activation. METHODS: In this study, intestinal I/R was induced by 60-min occlusion of the superior mesenteric artery in rats followed by 60-min reperfusion, and the rats were pretreated with a TNF-α inhibitor, pentoxifylline, or the TNF-α antibody infliximab. After surgery, part of the intestine was collected for histological analysis. The mucosal layer was harvested for RNA and protein extraction, which were used for further real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blotting analyses. The TNF-α expression, intestinal mucosal injury, cell apoptosis, activation of apoptotic protein and JNK signaling pathway were analyzed. RESULTS: I/R significantly enhanced expression of mucosal TNF-α at both the mRNA and protein levels, induced severe mucosal injury and cell apoptosis, activated caspase-9/caspase-3, and activated the JNK signaling pathway. Pretreatment with pentoxifylline markedly downregulated TNF-α at both the mRNA and protein levels, whereas infliximab pretreatment did not affect the expression of TNF-α induced by I/R. However, pretreatment with pentoxifylline or infliximab dramatically suppressed I/R-induced mucosal injury and cell apoptosis and significantly inhibited the activation of caspase-9/3 and JNK signaling. CONCLUSION: The results indicate there was a TNF-α-mediated JNK activation response to intestinal I/R injury.