Prevalence of osteoporosis among patients after stem cell transplantation: a systematic review and meta-analysis.

The prevalence of osteoporosis in post stem cell transplantation (SCT) is poorly defined. We performed a systematic review and meta-analysis to determine the prevalence of osteoporosis in patients with hematologic diseases who underwent SCT. PubMed, EMBASE, and Web of Science were searched (from inception to 30th April 2023) using Medical Subject Headlines to find studies that assessed the prevalence of osteoporosis among post SCT. Thirteen articles meeting the inclusion criteria were included in the analysis. The pooled prevalence rates of osteoporosis, osteopenia, and decreased bone mineral density (BMD) were determined to be 14.2% (95% CI 9.7-18.8), 36.0% (95% CI 23.8-48.2), and 47.8% (95% CI 36.6-58.9), respectively. Substantial heterogeneity was observed among the included studies (I² values ranged from 81% to 99%). Subgroup analyses revealed variations in prevalence based on gender, follow-up duration, age, region, sample size, and study quality. These findings suggest a high prevalence of osteoporosis in post-SCT patients. Given the negative impact of osteoporosis on prognosis and recipient survival, clinicians should prioritize preventive measures, early diagnosis, and effective treatments to minimize its impact.

A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects.

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen.

Efficacy and safety of combined Chinese and Western medicine in the treatment of knee osteoarthritis: a prospective, multicenter cohort study.

Purpose: To conduct a real-world evaluation of the efficacy and safety of combined Chinese and Western medicine in treating knee osteoarthritis (KOA). Methods: A multicenter, prospective cohort study design was employed, enrolling 450 KOA patients (Kellgren-Lawrence score of 3 or less). The patients were divided into a Western medicine treatment group (WM group) and a combined Western and traditional Chinese medicine treatment group (WM-CM group). A 6-week treatment plan was administered, and follow-up visits occurred at 2 weeks, 4 weeks, and 6 weeks after initiating treatment. The primary outcome indicator was the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score after 6 weeks of treatment. Secondary outcome indicators included WOMAC subscales for pain, stiffness, and joint function, visual analogue scale (VAS) score, physical component summary (PCS), mental component summary (MCS), and clinical effectiveness. The incidence of drug-related adverse events was used as a safety evaluation indicator. Results: A total of 419 patients were included in the final analysis: 98 in the WM group and 321 in the WM-CM group. The baseline characteristics of the two groups were comparable, except for the incidence of stiffness symptoms and stiffness scores. After 6 weeks of treatment, the WM-CM group exhibited superior results to the WM group in improving the total WOMAC score (24.71 ± 1.38 vs. 16.36 ± 0.62, p < 0.001). The WM-CM group also outperformed the WM group in WOMAC pain and joint function scores, VAS score, PCS score, MCS score, and clinical effectiveness (p < 0.05), which was consistent with the findings of the main evaluation index. Subgroup analysis indicated that the combined Chinese and Western medicine treatment showed more pronounced benefits in patients under 65 years of age and in those with a Kellgren-Lawrence (K-L) classification of 0-I. Throughout the study, no adverse effects were observed in either group. Conclusion: The combination of Chinese and Western medicine demonstrated superiority over Western medicine alone in relieving knee pain symptoms, improving knee function, and enhancing the quality of life for KOA patients with a K-L score of 3 or less. Moreover, the treatment exhibited a good safety profile. Clinical Trial Registration: (https://www.chictr.org.cn/), identifier (ChiCTR1900027175).

Efficacy and safety of subcutaneous semaglutide in adults with overweight or obese: a subgroup meta-analysis of randomized controlled trials.

Introduction: Semaglutide shows significant performance on weight reduction in several clinical trials. However, it is not clear what kind of administration frequency or dosage will achieve better effects. This study aims to explore the different therapeutic effect of semaglutide on weight control under the diverse administration circumstances. Methods: The PubMed, Embase, Web of Science, Cochrane Library, and the Clinical Trials.gov were searched from inception until 6 June, 2022 to include randomized controlled trials evaluating the Efficacy and safety of subcutaneous semaglutide in overweight or obese adults. Random effects or fixed effects model was conducted based on the heterogeneity among trials. Subgroup analysis was performed to identify the detailed effects under different intervention situations. Results and discussion: Our study included 13 RCTs involving 5,838 participants with 3,794 ones in semaglutide group and 2,044 in placebo group. Semaglutide was associated with a significant reduction on weight loss related outcomes, including the absolute value of weight loss (WMD -8·97, 95% CI -10·73 to -7·21), percentage of weight loss (WMD -10·00, 95% CI -11·99 to -8·00), body mass index (WMD-3·19, 95% CI -4·02 to -2·37) and waist circumference (WMD -7·21,95% CI -8·87 to -5·56). Subgroup analyses illustrated participants with high weekly dosage, long-term treatment duration and severe baseline BMI (Class II obesity) had a more remarkably decreasing on the main outcomes of weight loss (P for interaction<0·05). Total adverse reactions occurred more frequently in the daily administration group than that in the weekly group (P for interaction =0·01). During the treatment, the incidence rate of hypoglycemia was higher in the group without lifestyle intervention compared with that with lifestyle intervention (P for interaction =0·04). Interpretation Subcutaneous semaglutide had significant benefits on weight loss with reasonable safety in overweight or obese adults. Moreover, additional benefits on cardiometabolic profiles were also seen. We recommended semaglutide treatment to be coupled with lifestyle interventions, and target dose of 2·0 mg or more subcutaneously once weekly. Clinicians can choose suitable treatment schemes based on diverse individual situations. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=337099, identifier PROSPERO (CRD42022337099).

Association of MTHFR C677T polymorphism with primary open angle glaucoma: a Meta-analysis based on 18 case-control studies.

AIM: To systematically understand the genetic association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and primary open angle glaucoma (POAG). METHODS: A comprehensive literature search in Google Scholar, PubMed, Science Citation Index, Foreign Medical Literature Retrieval Service, Chinese National Knowledge Infrastructure and Wanfang Databases was performed to collect all eligible studies up to August 2019. Study selection, data abstraction and study quality evaluation were performed by two independent investigators. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association. RESULTS: Eighteen case-control studies including 2156 cases and 2201 controls were identified. There was no significant difference in the terms of MTHFR C677T polymorphism and POAG in the Caucasian population (for T vs C OR=1.11, 95%CI: 0.88 to 1.39; for TT vs CC OR=1.01, 95%CI: 0.76 to 1.36; for TT+TC vs CC OR=1.15, 95%CI: 0.84 to 1.58 and for TT vs TC+CC OR=1.02, 95%CI: 0.78 to 1.33). However, a significant effect was revealed in the Asian population (for T vs C OR=1.34, 95%CI: 1.12 to 1.59; for TT+TC vs CC OR=1.41, 95%CI: 1.14 to 1.76). CONCLUSION: Based on 18 eligible studies, we provide a correlation between MTHFR C677T polymorphism and POAG among the Asians subgroup indicating that the T allele or TT +TC genotype may play a critical role in POAG development in Asians.

Workplace bullying among operating room nurses in China: A cross-sectional survey.

PURPOSE: To investigate the prevalence and level of severity of workplace bullying among operating room nurses and to identify the risk factors that contribute to workplace bullying in operating room nurses in China. DESIGN AND METHODS: This descriptive research was conducted on 411 nurses from six medical centers in Harbin using a structured questionnaire. FINDINGS: The prevalence of workplace bullying was 15.8%. There were significant differences in workplace bullying by sex, hospital level, and marital status. Stepwise multiple regression analysis indicated that gender and marital status were significant determinants of workplace bullying. PRACTICE IMPLICATIONS: These findings portray a comprehensive landscape of workplace bullying among operating room nurses in China. Understanding the factors that influence workplace bullying may enhance the recognition and management of bullying behaviors.

Transcriptome analysis identified long non-coding RNAs involved in the adaption of yak to high-altitude environments.

The mechanisms underlying yak adaptation to high-altitude environments have been investigated using various methods, but no report has focused on long non-coding RNA (lncRNA). In the present study, lncRNAs were screened from the gluteus transcriptomes of yak and their transcriptional levels were compared with those in Sanjiang cattle, Holstein cattle and Tibetan cattle. The potential target genes of the differentially expressed lncRNAs between species/strains were predicted using cis and trans models. Based on cis-regulated target genes, no KEGG pathway was significantly enriched. Based on trans-regulated target genes, 11 KEGG pathways in relation to energy metabolism and three KEGG pathways associated with muscle contraction were significantly enriched. Compared with cattle strains, transcriptional levels of acyl-CoA dehydrogenase, acyl-CoA-binding protein, 3-hydroxyacyl-CoA dehydrogenase were relatively higher and those of glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate mutase 1, pyruvate kinase and lactate/malate dehydrogenase were relatively lower in yak, suggesting that yaks activated fatty acid oxidation but inhibited glucose oxidation and glycolysis. Besides, NADH dehydrogenase and ATP synthase showed lower transcriptional levels in yak than in cattle, which might protect muscle tissues from deterioration caused by reactive oxygen species (ROS). Compared with cattle strains, the higher transcriptional level of glyoxalase in yak might contribute to dicarbonyl stress resistance. Voltage-dependent calcium channel/calcium release channel showed a lower level in yak than in cattle strains, which could reduce the Ca2+ influx and subsequently decrease the risk of hypertension. However, levels of EF-hand and myosin were higher in yak than in cattle strains, which might enhance the negative effects of reduced Ca2+ on muscle contraction. Overall, the present study identified lncRNAs and proposed their potential regulatory functions in yak.

What is the impact of rural-to-urban migration on exclusive breastfeeding: a population-based cross-sectional study.

BACKGROUND: In China, less than one third of infants under 6 months of age are being exclusively breastfed. Maternal rural-to-urban migration contributes to these low rates of breastfeeding practices. Therefore, the aim of this study was to assess the prevalence of breastfeeding practices and associated factors among rural-to-urban migrant children and local children with infants aged 0-12 months in China, 2018. METHODS: Data were collected from a population-based cross-sectional survey in 2018 that included 6995 infants from eight urban areas (four metropolis and four medium sized/small cities) in China. The prevalence of breastfeeding practices was calculated using a 24-h recall questionnaire for all infants aged under 12 months. Logistic regression was conducted to examine the association between the prevalence of breastfeeding practices and maternal migrant status, after adjusting for sociodemographic characteristics, mother-infant health information and supportive information. For exclusive breastfeeding, we further analyzed its association with maternal rural-to-urban migration, stratified by maternal education level, maternal resident place and maternal ethnicity, respectively. RESULTS: The overall prevalence of ever breastfeeding, exclusive breastfeeding, predominant breastfeeding and age-appropriate breastfeeding (exclusive breastfeeding of infants under 6 months of age and complementary feeding from six to 12 months of age) was 97.51, 29.84, 59.89 and 45.07%, respectively. Rural-to-urban migrant children were less likely to be exclusively breastfed compared to local children (AOR 0.81, 95% CI 0.68, 0.95). Stratified by different sociodemographic variables, a negative association between exclusive breastfeeding and rural-to-urban migration was only found in the group with high education level, in the group living in metropolis and in the group of minorities, respectively. CONCLUSIONS: The overall prevalence of breastfeeding practices was low in both rural-to-urban migrant children and local children. Besides common strategies, special approaches should be provided for urban highly educated migrants.

How Does Attention Alter Length Perception? A Prism Adaptation Study.

How perceived size (length) of an object is influenced by attention is in debate. Prism adaptation (PA), as a type of sensory motor adaptation, has been shown to affect performance on a variety of spatial tasks in both neglect patient and healthy individuals. It has been hypothesized that PA's effects might be mediated by attentional mechanisms. In this study, we used PA to laterally shift spatial attention, and employed a precise psychophysical procedure to examine how the perceptual length of lines was influenced by this attentional shifting. Participants were presented with two separate lines in the left and right visual fields, and compared the length of the two lines. Forty-five healthy participants completed this line-length judgment task before and after a short period of adaptation to either left- (Experiment 1) or right-shifting (Experiment 2) prisms, or control goggles that did not shift the visual scene (Experiment 3). We found that participants initially tended to perceive the line presented in the left to be longer. This leftward bias of length perception was reduced by a short period of visuomotor adaptation to the left-deviating PA. However, for the right-shifting PA and plain glass goggles conditions, the initial length perception bias to the left line was unaffected. Mechanisms of this asymmetric effect of PA was discussed. Our results demonstrate that the length perception of a line can be influenced by a simple visuomotor adaptation, which might shift the spatial attention. This finding is consistent with the argument that attention can alter appearance.

Influence of total flavonoids derived from Choerospondias axillaris folium on aconitine-induced antiarrhythmic action and hemodynamics in Wistar rats.

It is well known that various traditional Chinese medicines produce antiarrhythmic actions. The aims of this study were to examine whether total flavones derived from Choerospondias axillaris folium (TFCF) also produced antiarrhythmic effects using a rat model of aconitine-induced arrhythmia and to compare these observations with the effects of total flavones of Choerospondias axillaris fructus (TFC). Wistar rats were orally administered TFC (0.2 g/kg) or TFCF (0.1, 0.2, or 0.4 g/kg) daily for 7 d. Subsequently, aconitine iv at 25 µg/kg was used to induce arrhythmia in these animals. Control (C) physiological saline and positive verapamil rats were also administered orally. The starting times of ventricular ectopic beats (VE), ventricular tachycardia (VT), ventricular fibrillation (VF), and heart arrest (HA) were recorded. In comparison to C, TFCF and TFC significantly prolonged the starting time of VE, VT, VF, and HA induced by aconitine. With respect to hemodynamics, TFC and high-dose TFCF were effective in reducing HR without associated changes in BP in all groups. TFC and TFCF decreased left ventricular systolic pressure (LVSP) and maximal velocity rate of ventricular pressure (+dp/dt max and -dp/dt min) with no marked effect on left ventricular end diastolic pressure (LVEDP) and -dp/dtmin. Data demonstrated that TFCF and TFC were equally effective in diminishing the aconitine-mediated arrhythmias. In addition, TFCF and TFC produced a similar reduction in HR with no accompanying change in BP. These findings indicate that the TFCF- and TFC-induced alterations may be attributed to inhibition of ventricular contraction without altering ventricular diastolic function.

Angiotensinogen polymorphism and ischemic stroke risk.

The angiotensinogen M235T polymorphism was associated with ischemic stroke risk. However, the results were controversial. Thus, a meta-analysis was conducted. NCBI, Medline, Web of Science and Embase databases were systematically searched. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random-effects models. There was a significant association between angiotensinogen M235T polymorphism and ischemic stroke risk (OR = 1.69; 95% CI, 1.35-2.11; P < 0.001). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with ischemic stroke in Asian (OR = 1.85; 95% CI, 1.45-2.35; P < 0.001). In the age subgroup, we found that angiotensinogen M235T polymorphism could increase both early-onset ischemic stroke risk (OR = 1.88; 95% CI, 1.33-2.43; P < 0.001) and late-onset ischemic stroke risk (OR = 1.20; 95% CI, 1.01-1.39; P = 0.04). This meta-analysis suggested that angiotensinogen M235T polymorphism was associated with ischemic stroke.

MicroRNA-34a contributes to the protective effects of glucagon-like peptide-1 against lipotoxicity in INS-1 cells.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) reduces fatty acid-induced beta-cell lipotoxicity in diabetes; however, the explicit mechanisms underlying this process are not fully understood. This study was designed to investigate the involvement of microRNA, which regulates gene expression by the sequence-specific inhibition of mRNA transcription in the GLP-1 mediation of beta-cell function. METHODS: The cell viability and apoptosis were determined using an methyl thiazoleterazolium (MTT) assay and flow cytometry. The expression of genes involved in beta-cell function, including microRNA-34a and sirtuin 1, were investigated using real-time PCR. The underlying mechanisms of microRNA-34a were further explored using cell-transfection assays. RESULTS: A 24-hours incubation of INS-1 cells with palmitate significantly decreased cell viability, increased cell apoptosis and led to the activation of microRNA-34a and the suppression of sirtuin 1. A co-incubation with GLP-1 protected the cells against palmitate-induced toxicity in association with a reduction in palmitate-induced activation of microRNA-34a. Furthermore, palmitate-induced apoptosis was significantly increased in cells that were infected with microRNA-34a mimics and decreased in cells that were infected with microRNA-34a inhibitors. CONCLUSION: MicroRNA-34a is involved in the mechanism of GLP-1 on the modulation of beta-cell growth and survival.

[Changes of proteomic spectra of total flavones of Hippophae rhamnoides on myocardial protection].

OBJECTIVE: To study the mechanisms of the anti-myocardial ischemia of total flavones of Hippophae rhamnoides (TFH) at the level of proteome. METHOD: Surface enhanced laser desorption/ionization (SELDI) mass spectrometry with protein chip IMAC3, SAX2 and NP20 was performed to compare the differentially expressed protein in myocardial ischemia in the TFH-treated groups with the 0.9% sodium chloride groups. Protein chips were examined in PBS II - C protein chip reader (ciphergen ciosystem inc) and the protein profiling was analyzed by Proteinchip Software 3. 0. 2. RESULT: The revealed six peaks had significant difference between the TFH-treated groups and the control groups, one of which were up-regulated in the TFH-treated groups, and the other were down-regulated. And in these six distinct proteins, there were four proteins on the IMAC3 chips and one protein on the SAX2 chips. CONCLUSION: The TFH could prevent the myocardium from ischemia via regulating expression of different proteins.

Sex differences in response to immunonutrition in sepsis.

BACKGROUND: Cell-mediated immune response is superior in females compared to males. Whether sex differences influenced mortality in sepsis while on immune-enhancing nutrients was investigated. MATERIALS AND METHODS: Seventy-two non-orchitectomized male and non-oophorectomized female rats (n = 36/group) were randomized into four groups. Rats were fed either an immune-enhancing diet or control diet for five days. Sepsis was induced with caecal ligation and puncture (CLP). An additional group of orchitectomized and oophorectomized rats (n = 36/group) were divided into four groups; fed either an immune-enhancing or control diet of one month, then following castration. Sepsis was induced with CLP. The influence of immune-enhancing nutrients on the effect of the rat's sex on mortality rates and serum cytokines were compared. RESULTS: Non-orchitectomized male rats had a decreased mortality (88.9% vs. 16.7%) on immune-enhancing diet. Low mortality among non-oophorectomized female rats persisted, on immune-enhancing diet (27.8% vs. 11.1%). Orchitectomized rats demonstrated reduced mortality (88.8% vs. 50%) on immune-enhancing diet. Oophorectomized rats showed a similar trend (55.6% vs. 44.4%). Orchitectomy increased mortality in spite of immune-enhancing diet (50% vs. 16.7%). Oophorectomy increased mortality on immune-enhancing diet (44.4% vs. 11.1%). Circulating IL-1beta was higher in non-oophorectomized female rats on control diet compared to immune-enhancing diet. Non-orchitectomized male and non-oophorectomized female rats had similar increases in IL-10 on immune-enhancing diet. CONCLUSIONS: Mortality rates on immunonutrition were less in male than female rats following sepsis. Orchitectomy did not confer an advantage for septic rats. Sex hormone was more important than immunonutrition in septic female rats.

[Comparing the actions of the three flavone ingredients in choerospondias axillaris on arrhythmias induced by aconitine].

OBJECTIVE: To compare the actions of the three flavone ingredients in choerospondias axillaris on arrhythmias Induced by aconitine. METHOD: Langendorff perfuse was applied in the experiment, the antiarrhythmic action was to study by using aconitine on the the isolated heart; The antiarrhythmic action of the three flavone ingredients in choerospondias axillaris was to study by using i.v. aconitine in rat to induce arrhythmias. RESULT: Compared with the NS group, sample 1 and sample 2 both significantly prolonged the beginning time of VF of isolated heart and increased the dosage of aconitine, sample 3 reduced the beginning time of VF of isolated heart and decreased the dosage of aconitine, sample 1 and sample 2 both greatly prolonged the beginning time of VE, VT, VF, HA; sample 3 greatly reduced the beginning time of VT,VF. The actions of the three samples were in a concentration-dependent way. CONCLUSION: Sample 1 and sample 2 both resisted the occurrence of arrhythmias induced by aconitine, sample 3 markedly promoted the occurrence of arrhythmias induced by aconitine.

Damaging effect of cigarette smoke extract on primary cultured human umbilical vein endothelial cells and its mechanism.

OBJECTIVE: To investigate the cellular effects of cigarette smoke extract (CSE) on primarily cultured human umbilical vein endothelial cells (HUVEC). METHODS: The effects of CSE (5%-20%) and nicotine (10(-4) mol/L) on HUVEC viability, proliferation, angiogenesis and apoptosis were observed. RESULTS: CSE decreased HUVEC survival rate and angiogenesis after 24 h as well as its proliferation after 48 h in a dose-dependent manner. Moreover, CSE induced apoptosis of HUVEC as indicated in condensation of nuclear chromatin and the presence of hypodiploid DNA. HUVEC incubated with CSE for 24 h gave a significant decrease in the expression of Bcl-2 as well as the decline in the Bcl-2/Bax ratio accompanied with the loss of mitochondrial membrane potential and excess cytosolic calcium. Our study also observed that p53 protein level decreased, rather than increased in cells treated with CSE. Nicotine had no discernible inhibitory effects on the above indices of HUVEC. CONCLUSION: Exposure to CSE other than nicotine causes inhibition of viability, proliferation and differentiation of HUVEC. CSE-induced HUVEC injury is mediated in partthrough accelerated apoptosis but independent of p53 pathway. It appears that mitochondria have played a key role in the apoptosis of HUVEC induced by CSE.

Injury of mouse brain mitochondria induced by cigarette smoke extract and effect of vitamin C on it in vitro.

OBJECTIVE: To investigate the toxicity of cigarette smoke extract (CSE) and nicotine on mouse brain mitochondria as well as the protective effect of vitamin C in vitro. METHOD: Mouse brain mitochondria in vitro was incubated with CSE or nicotine in the absence or presence of vitamin C for 60 minutes, and the changes of mitochondrial function and structure were measured. RESULTS: CSE inhibited mitochondrial ATPase and cytochrome C oxidase activities in a dose-dependent manner. However, no significant changes in the peroxidation indices were observed when mitochondrial respiratory enzymes activity was inhibited, and protection of mitochondria from CSE-induced injury by vitamin C was not displayed in vitro. The effect of CSE on mouse brain mitochondria swelling response to calcium stimulation was dependent on calcium concentrations. CSE inhibited swelling of mitochondria at 6.5 mumol/L Ca2+, but promoted swelling response at 250 mumol/L Ca2+. Nicotine, the major component of cigarette smoke, showed no significant damage in mouse brain mitochondria in vitro. The CSE treatment induced mitochondrial inner membrane damage and vacuolization of the matrix, whereas the outer mitochondrial membrane appeared to be preserved. CONCLUSION: The toxic effect of CSE on brain mitochondria may be due to its direct action on enzymatic activity rather than through oxygen free radical injury. Nicotine is not the responsible component for the toxicity of CSE to brain mitochondria.