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International Journal of Environmental... May 2024Although seatbelt use is known to reduce motor vehicle occupant crash injury and death, rear-seated adult occupants are less likely to use restraints. This study...
Although seatbelt use is known to reduce motor vehicle occupant crash injury and death, rear-seated adult occupants are less likely to use restraints. This study examines risk and protective factors associated with injury severity in front- and rear-seated adults involved in a motor vehicle crash in New York State. The Crash Outcome Data Evaluation System (CODES) (2016-2017) was used to examine injury severity in front- and rear-seated occupants aged 18 years or older ( = 958,704) involved in a motor vehicle crash. CODES uses probabilistic linkage of New York State hospitalization, emergency department, and police and motorist crash reports. Multivariable logistic regression models with MI analyze employed SAS 9.4. Odds ratios are reported as OR with 95% CI. The mortality rate was approximately 1.5 times higher for rear-seated than front-seated occupants (136.60 vs. 92.45 per 100,000), with rear-seated occupants more frequently unrestrained than front-seated occupants (15.28% vs. 1.70%, < 0.0001). In adjusted analyses that did not include restraint status, serious injury/death was higher in rear-seated compared to front-seated occupants (OR:1.272, 1.146-1.412), but lower once restraint use was added (OR: 0.851, 0.771-0.939). Unrestrained rear-seated occupants exhibited higher serious injury/death than restrained front-seated occupants. Unrestrained teens aged 18-19 years old exhibit mortality per 100,000 occupants that is more similar to that of the oldest two age groups than to other young and middle-aged adults. Speeding, a drinking driver, and older vehicles were among the independent predictors of serious injury/death. Unrestrained rear-seated adult occupants exhibit higher severe injury/death than restrained front-seated occupants. When restrained, rear-seated occupants are less likely to be seriously injured than restrained front-seated occupants.
Topics: Humans; Accidents, Traffic; Adult; Middle Aged; New York; Female; Male; Young Adult; Aged; Adolescent; Wounds and Injuries; Risk Factors; Protective Factors; Aged, 80 and over; Seat Belts
PubMed: 38928910
DOI: 10.3390/ijerph21060663 -
Diagnostics (Basel, Switzerland) Jun 2024A total of 300 research participants-200 consecutive patients diagnosed with dyslipidemia (100 statin (+), treated for at least five years, and 100 statin (-)) and 100...
A total of 300 research participants-200 consecutive patients diagnosed with dyslipidemia (100 statin (+), treated for at least five years, and 100 statin (-)) and 100 healthy controls-were included in this observational study. The aim of the study was to deliver insights into the relationship between the long-term use of statins for dyslipidemia and gallstone disease (GSD), as well as insights into the background particularities of the gut microbiota. All study participants underwent clinical examination, laboratory workups, stool microbiology/stool 16S r RNA, next-generation sequencing, and abdominal ultrasound/CT exams. Results: The research participants presented with similarities related to age, gender, and location. Patients displayed comparable heredity for GSs, metabolic issues, and related co-morbidities. Gut dysbiosis (DB) was present in 54% of the statin (-) patients vs. 35% of the statin (+) patients ( = 0.0070). GSs were present in 14% of patients in the statin (-) group vs. 5% of patients in the statin (+) group ( = 0.0304). Severe dysbiosis, with a significant reduction in biodiversity, an increase in LPS (+) bacteria, and a notable decrease in mucin-degrading bacteria, mucosa-protective bacteria, and butyrate-producing bacteria were observed in the statin (-) group. Strong positive correlations between GSD and diabetes/impaired glucose tolerance (r = 0.3368, = 0.0006), obesity (r = 0.3923, < 0.0001), nonalcoholic fatty liver disease (r = 0.3219, = 0.0011), and DB (r = 0.7343, < 0.0001), as well as significant negative correlations between GSD and alcohol use (r = -0.2305, = 0.0211), were observed. The multiple regression equation demonstrated that only DB (95% CI: 0.3163 to 0.5670; < 0.0001) and obesity (95% CI: 0.01431 to 0.2578; = 0.0289) were independent risk factors predicting GSD in the group of patients treated with statins. Conclusion: The long-term use of statins in dyslipidemic patients was associated with a low risk of developing GSs. The gut microbiota associated with a long-term use of statins in dyslipidemic patients was characterized by a low risk of developing an imbalance of various functional bacteria and alterations in the metabolic microbiota. DB and obesity were found to be independent risk factors predicting GSD in statin (+) patients.
PubMed: 38928650
DOI: 10.3390/diagnostics14121234 -
Brain Sciences Jun 2024Cerebral amyloid angiopathy is characterized by a weakening of the small- and medium-sized cerebral arteries, as their smooth muscle cells are progressively replaced...
Cerebral amyloid angiopathy is characterized by a weakening of the small- and medium-sized cerebral arteries, as their smooth muscle cells are progressively replaced with acellular amyloid β, increasing vessel fragility and vulnerability to microhemorrhage. In this context, an aberrant overactivation of the complement system would further aggravate this process. The surface protein CD59 protects most cells from complement-induced cytotoxicity, but expression levels can fluctuate due to disease and varying cell types. The degree to which CD59 protects human cerebral vascular smooth muscle (HCSM) cells from complement-induced cytotoxicity has not yet been determined. To address this shortcoming, we selectively blocked the activity of HCSM-expressed CD59 with an antibody, and challenged the cells with complement, then measured cellular viability. Unblocked HCSM cells proved resistant to all tested concentrations of complement, and this resistance decreased progressively with increasing concentrations of anti-CD59 antibody. Complete CD59 blockage, however, did not result in a total loss of cellular viability, suggesting that additional factors may have some protective functions. Taken together, this implies that CD59 plays a predominant role in HCSM cellular protection against complement-induced cytotoxicity. The overexpression of CD59 could be an effective means of protecting these cells from excessive complement system activity, with consequent reductions in the incidence of microhemorrhage. The precise extent to which cellular repair mechanisms and other complement repair proteins contribute to this resistance has yet to be fully elucidated.
PubMed: 38928601
DOI: 10.3390/brainsci14060601 -
Brain Sciences Jun 2024Rotenone (RTN) induces neurotoxicity and motor dysfunction in rats, mirroring the pathophysiological traits of Parkinson's disease (PD), including striatal oxidative...
Rotenone (RTN) induces neurotoxicity and motor dysfunction in rats, mirroring the pathophysiological traits of Parkinson's disease (PD), including striatal oxidative stress, mitochondrial dysfunction, and changes in neural structure. This makes RTN a valuable model for PD research. Berberine (BBR), an isoquinoline alkaloid recognized for its antioxidative, anti-inflammatory, and neuroprotective properties, was evaluated for its ability to counteract RTN-induced impairments. Rats received subcutaneous RTN at 0.5 mg/kg for 21 days, resulting in weight loss and significant motor deficits assessed through open-field, bar catalepsy, beam-crossing, rotarod, and grip strength tests. BBR, administered orally at 30 or 100 mg/kg doses, one hour prior to RTN exposure for the same duration, effectively mitigated many of the RTN-induced motor impairments. Furthermore, BBR treatment reduced RTN-induced nitric oxide (NO) and lipid peroxidation (LPO) levels, bolstered antioxidative capacity, enhanced mitochondrial enzyme activities (e.g., succinate dehydrogenase (SDH), ATPase, and the electron transport chain (ETC)), and diminished striatal neuroinflammation and apoptosis markers. Notably, the co-administration of trigonelline (TGN), an inhibitor of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway, significantly attenuated BBR's protective effects, indicating that BBR's neuroprotective actions are mediated via the Nrf2 pathway. These results underscore BBR's potential in ameliorating motor impairments akin to PD, suggesting its promise in potentially delaying or managing PD symptoms. Further research is warranted to translate these preclinical findings into clinical settings, enhancing our comprehension of BBR's therapeutic prospects in PD.
PubMed: 38928596
DOI: 10.3390/brainsci14060596 -
Brain Sciences Jun 2024The COVID-19 pandemic has brought attention to the long-term consequences of the virus, particularly the persistent symptoms that characterize long COVID. This syndrome,... (Review)
Review
The COVID-19 pandemic has brought attention to the long-term consequences of the virus, particularly the persistent symptoms that characterize long COVID. This syndrome, which can last for months after the initial infection, includes a range of neurological and neuropsychiatric manifestations that have significant implications for brain health and dementia research. This review explores the current understanding of long COVID's cognitive, neurological, and psychiatric symptoms and their potential impact on brain stimulation and neuroimaging studies. It argues that researchers must adapt their study designs and screening processes to account for the confounding effects of long COVID and ensure the accuracy and reliability of their findings. To advance the understanding of this condition and its long-term effects on brain health, the review proposes a series of strategies, including the development of standardized screening tools, the investigation of underlying mechanisms, and the identification of risk factors and protective factors. It also emphasizes the importance of collaborative research efforts and international data sharing platforms in accelerating the pace of discovery and developing targeted interventions for individuals with long COVID. As the prevalence of this condition continues to grow, it is imperative that the neuroscience community comes together to address this challenge and support those affected by long COVID.
PubMed: 38928587
DOI: 10.3390/brainsci14060587 -
International Journal of Molecular... Jun 2024Oil-Gan is the fruit of the genus L. The fruits have excellent effects on health care and development values. There are many methods for the management of diabetic...
Oil-Gan is the fruit of the genus L. The fruits have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN throughout the disease course. The primary aim of this study was to examine the protective effects (including analyses of urine and blood, and inflammatory cytokine levels) and mechanisms of the ethyl acetate extract of (EPE) on db/db mice, an animal model of diabetic nephropathy; the secondary aim was to examine the expression levels of p- protein kinase Cα (PKCα)/t-PKCα in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included a vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. The administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing 3 (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. A histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model.
Topics: Animals; Diabetic Nephropathies; Plant Extracts; Mice; Phyllanthus emblica; Male; Disease Models, Animal; Diabetes Mellitus, Experimental; Acetates; Vascular Endothelial Growth Factor A; Kidney; Transforming Growth Factor beta1; Protein Kinase C-alpha; Blood Glucose
PubMed: 38928391
DOI: 10.3390/ijms25126686 -
International Journal of Molecular... Jun 2024Chlorpyrifos (CPF) is a widely used organophosphate insecticide, though its excessive use causes environmental contamination, raising concerns about its adverse effects...
Chlorpyrifos (CPF) is a widely used organophosphate insecticide, though its excessive use causes environmental contamination, raising concerns about its adverse effects on human health. In this regard, stands out as a promising candidate for counteracting chemical 'contaminant' toxicity thanks to its therapeutic properties. Therefore, our study aimed to investigate the potential of an ethanolic extract (UDE) to mitigate chlorpyrifos-induced toxicity. Eight compounds in the ethanolic extract have been identified, most of which present significant potential as antioxidant, anti-inflammatory, and neuroprotective agents. Chlorpyrifos exposure altered hatching rates, increased the incidence of teratogenic effects, and upregulated the expression of brain-derived neurotrophic factor (Bdnf) in zebrafish larvae telencephalon. On the other hand, demonstrated a preventive effect against CPF-induced teratogenicity, which is expressed by a lower morphological deformity rate. Moreover, the UDE showed a rather protective effect, maintaining the physiological condition of the telencephalon. Additionally, CPF altered the locomotor behavior of larvae, which was characterized by irregular swimming and increased activity. This defective behavioral pattern was slightly attenuated by the UDE. Our findings suggest that the UDE possesses significant protective properties against CPF-induced toxicity, probably conferred by its natural antioxidant and anti-inflammatory contents. Still, further research is needed to elucidate the recruited mechanisms and implicated pathways on UDE's protective effects.
Topics: Animals; Zebrafish; Chlorpyrifos; Plant Extracts; Larva; Urtica dioica; Antioxidants; Insecticides; Telencephalon
PubMed: 38928336
DOI: 10.3390/ijms25126631 -
International Journal of Molecular... Jun 2024Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the...
New Insights into Hepatic and Intestinal Microcirculation and Pulmonary Inflammation in a Model of Septic Shock and Venovenous Extracorporeal Membrane Oxygenation in the Rat.
Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the use of V-V ECMO in septic shock remains controversial. The effect of ECMO-induced inflammation on the microcirculation of the intestine, liver, and critically damaged lungs is unknown. Therefore, the aim of this study was to measure the hepatic and intestinal microcirculation and pulmonary inflammatory response in a model of V-V ECMO and septic shock in the rat. Twenty male Lewis rats were randomly assigned to receive V-V ECMO therapy or a sham procedure. Hemodynamic data were measured by a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by the intravenous infusion of lipopolysaccharide (1 mg/kg). During V-V ECMO therapy, rats received lung-protective ventilation. The hepatic and intestinal microcirculation was assessed by micro-lightguide spectrophotometry after median laparotomy for 2 h. Systemic and pulmonary inflammation was measured by enzyme-linked immunosorbent assays of plasma and bronchoalveolar lavage (BAL), respectively, which included tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-10, C-X-C motif ligand 2 (CXCL2), and CXCL5. Reduced oxygen saturation and relative hemoglobin concentration were measured in the hepatic and intestinal microcirculation during treatment with V-V ECMO. These animals also showed increased systolic, mean, and diastolic blood pressures. While no differences in left ventricular ejection fraction were observed, animals in the V-V ECMO group presented an increased heart rate, stroke volume, and cardiac output. Blood gas analysis showed dilutional anemia during V-V ECMO, whereas plasma analysis revealed a decreased concentration of IL-10 during V-V ECMO therapy, and BAL measurements showed increased concentrations of TNF-α, CXCL2, and CXCL5. Rats treated with V-V ECMO showed impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Despite lung-protective ventilation, increased pulmonary inflammation was recognized during V-V ECMO therapy in septic shock.
Topics: Animals; Microcirculation; Extracorporeal Membrane Oxygenation; Male; Rats; Shock, Septic; Rats, Inbred Lew; Intestines; Liver; Disease Models, Animal; Pneumonia; Hemodynamics; Tumor Necrosis Factor-alpha
PubMed: 38928327
DOI: 10.3390/ijms25126621 -
International Journal of Molecular... Jun 2024Chemotherapy resistance in cancer is an essential factor leading to high mortality rates. Tumor multidrug resistance arises as a result of the autophagy process. Our...
Chemotherapy resistance in cancer is an essential factor leading to high mortality rates. Tumor multidrug resistance arises as a result of the autophagy process. Our previous study found that compound 1-nitro-2 acyl anthraquinone-leucine (C2) exhibited excellent anti-colorectal cancer (CRC) activity involving autophagy and apoptosis-related proteins, whereas its underlying mechanism remains unclear. A notable aspect of this study is how C2 overcomes the multidrug susceptibility of HCT116/L-OHP, a colon cancer cell line that is resistant to both in vitro and in vivo oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP). In a xenograft tumor mouse model, we discovered that the mixture of C2 and L-OHP reversed the resistance of HCT116/L-OHP cells to L-OHP and inhibited tumor growth; furthermore, C2 down-regulated the gene expression levels of and and decreased drug efflux activity. It is important to note that while C2 re-sensitized the HCT116/L-OHP cells to L-OHP for apoptosis, it also triggered a protective autophagic pathway. The expression levels of cleaved caspase-3 and Beclin 1 steadily rose. Expression of PI3K, phosphorylated AKT, and mTOR were decreased, while p53 increased. We demonstrated that the anthraquinone derivative C2 acts as an L-OHP sensitizer and reverses resistance to L-OHP in HCT116/L-OHP cells. It suggests that C2 can induce autophagy in HCT116/L-OHP cells by mediating p53 and the PI3K/AKT/mTOR signaling pathway.
Topics: Humans; TOR Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Animals; Oxaliplatin; Phosphatidylinositol 3-Kinases; Autophagy; Anthraquinones; Signal Transduction; Mice; HCT116 Cells; Apoptosis; Xenograft Model Antitumor Assays; Antineoplastic Agents; Drug Resistance, Neoplasm; Mice, Nude; Cell Line, Tumor
PubMed: 38928176
DOI: 10.3390/ijms25126468 -
International Journal of Molecular... Jun 2024Allergic diseases are showing increasing prevalence in Western societies. They are characterized by a heightened reactivity towards otherwise harmless environmental... (Review)
Review
Allergic diseases are showing increasing prevalence in Western societies. They are characterized by a heightened reactivity towards otherwise harmless environmental stimuli. Allergic diseases showing a wide range of severity of symptoms have a significant impact on the quality of life of affected individuals. This study aims to highlight the mechanisms that induce these reactions, how they progress, and which prenatal factors influence their development. Most frequently, the reaction is mediated by immunoglobulin E (IgE) produced by B cells, which binds to the surface of mast cells and basophils and triggers an inflammatory response. The antibody response is triggered by a shift in T-cell immune response. The symptoms often start in early childhood with eczema or atopic dermatitis and progress to allergic asthma in adolescence. An important determinant of allergic diseases seems to be parental, especially maternal history of allergy. Around 30% of children of allergic mothers develop allergic sensitization in childhood. Genes involved in the regulation of the epithelial barrier function and the T-cell response were found to affect the predisposition to developing allergic disorders. Cord blood IgE was found to be a promising predictor of allergic disease development. Fetal B cells produce IgE starting at the 20th gestation week. These fetal B cells could be sensitized together with mast cells by maternal IgE and IgE-allergen complexes crossing the placental barrier via the low-affinity IgE receptor. Various factors were found to facilitate these sensitizations, including pesticides, drugs, exposure to cigarette smoke and maternal uncontrolled asthma. Prenatal exposure to microbial infections and maternal IgG appeared to play a role in the regulation of T-cell response, indicating a protective effect against allergy development. Additional preventive factors were dietary intake of vitamin D and omega 3 fatty acids as well as decreased maternal IgE levels. The effect of exposure to food allergens during pregnancy was inconclusive, with studies having found both sensitizing and protective effects. In conclusion, prenatal factors including genetics, epigenetics and fetal environmental factors have an important role in the development of allergic disorders in later life. Children with a genetic predisposition are at risk when exposed to cigarette smoke as well as increased maternal IgE in the prenatal period. Maternal diet during pregnancy and immunization against certain allergens could help in the prevention of allergy in predisposed children.
Topics: Humans; Pregnancy; Female; Hypersensitivity; Prenatal Exposure Delayed Effects; Immunoglobulin E; B-Lymphocytes
PubMed: 38928067
DOI: 10.3390/ijms25126359