Accuracy of self-perceived cardiovascular disease risk and factors predicting risk underestimation in perimenopausal and postmenopausal women in Ismailia, Egypt.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death globally, with women at higher risk after menopause. This increased risk is attributed to both aging and hormonal changes. Prior research has established a link between CVD risk perception and adopting healthy behaviors to prevent CVD. This study aimed to assess the accuracy of self-perceived CVD risk in perimenopausal and postmenopausal women, and to identify factors that predict CVD risk underestimation among them. METHODS: A cross-sectional study was conducted in the administrative sectors of Suez Canal University campus in Ismailia, Egypt, over a period of eight months starting in July 2022. A total of 390 eligible women (employees and workers) were randomly selected. Participants were interviewed to obtain data on demographics, medical history, self-perceived risk of CVD, self-perceived general health, awareness of factors that increase the risk of developing CVD, perceived stress, health literacy, numeracy, and self-perceived 10-year risk of developing major cardiovascular events. They also underwent measurements of blood pressure, weight, and height. The updated 2019 WHO/CVD risk non-laboratory-based prediction chart for the North Africa and Middle East Region was used to predict the 10-year risk of major cardiovascular events for the study participants. Risk accuracy was measured by comparing self-perceived CVD risk with predicted CVD risk. RESULTS: The ratio of self-perceived to predicted moderate/high CVD risk was 27.7% to 44.3%, respectively. The accuracy of CVD risk perception was 68.2%. Kappa analysis results showed fair and significant agreement between self-perceived and predicted CVD risk (kappa ± SE = 35.9 ± 4.1%, p < 0 .001). The proportion of women who underestimated their risks was 24.1%. Of those in the high-risk group, 93.3% underestimated their CVD risk, compared to 50.6% in the moderate-risk group. Factors that significantly predicted CVD risk underestimation included being married (aOR 14.5; 95% CI 1.4-149.9), low income (aOR 2.321; 95% CI 1.09-4.909), high BMI (aOR 4.78; 95% CI 1.9-11.9), hypertension (aOR 3.5; 95% CI 2-6.2), and old age (aOR 1.46; 95% CI 1.3-1.6). CONCLUSIONS: Approximately one-third of our study participants misperceived their CVD risk; of those who did, 75.8% underestimated it. Marital status, old age, low income, high BMI, and hypertension strongly predicted CVD risk underestimation. These findings identified the menopausal women subgroups that could benefit from targeted health interventions designed to reduce CVD risk underestimation and improve risk accuracy.

Comparative effect of deliberate hypotensive anesthesia using nitroglycerine vs. phentolamine on event related potentials and cognitive functions in patients undergoing septoplasty: a randomized controlled trial.

BACKGROUND: Postoperative cognitive dysfunction is a noteworthy complication of deliberate hypotensive anesthesia. The aim of this work was to compare the effect of deliberate hypotensive anesthesia using nitroglycerine versus phentolamine on event-related potentials and cognitive function in patients undergoing septoplasty surgery. METHODS: This prospective randomized controlled trial was conducted on 80 patients indicated for septoplasty under general anesthesia; 40 patients received intra-operative Nitroglycerine and 40 patients received intra-operative Phentolamine. Cognitive assessment (using Paired Associate Learning test (PALT) and Benton Visual Retention test (BVRT)) and P300 recording were done for all included patients pre-operatively and one week postoperatively. RESULTS: The scores of PALT and Benton BVRT significantly declined one week following surgery in both Nitroglycerine and Phentolamine groups. There was no statistically significant difference between Nitroglycerine and Phentolamine groups in the postoperative decline in either PALT or BVRT (P-value = 0.342, 0.662 respectively). The values of P300 latency showed a significant delay one week following surgery in both Nitroglycerine and Phentolamine groups (P-value ≤ 0.001, 0.001), but in Nitroglycerine group, the delay is significantly higher than in Phentolamine group (P-value = 0.003). The values of P300 amplitude significantly decreased one week following surgery in both Nitroglycerine and Phentolamine groups (P-value ≤ 0.001, 0.001), but there was no statistically significant difference between Nitroglycerine and Phentolamine groups (P-value = 0.099). CONCLUSION: Phentolamine is preferred over nitroglycerin in deliberate hypotensive anesthesia because it has less harmful effect on cognitive function than nitroglycerin.

Impact of corticosteroid administration on the response of exposed dental pulp to capping with bioactive cements-experimental study on mongrel dogs.

BACKGROUND: Corticosteroids are commonly used as a treatment for a variety of pathological conditions, however, systemic corticosteroid administration has adverse effects including impaired immune response and wound healing. Such complications may affect pulp healing after direct pulp capping. The current study evaluated the influence of corticosteroids on the healing ability of exposed dogs' dental pulps after direct pulp capping (DPC) with bioactive materials. METHODS: Ten healthy male dogs were assigned randomly into two groups, 5 dogs each: group I represent the control group which did not receive any medication, and group II was given corticosteroid for 45 days before DPC and till the dogs were euthanized (n = 75 teeth for each group). Following mechanical exposure, the pulps were randomly capped with either Ca(OH)2, MTA, or Biodentine. The pulpal tissues' reaction to the capping materials was evaluated 65 days postoperatively according to the following parameters: calcific bridge formation, pulpal inflammation, pulp necrosis, and bacterial infiltration. RESULTS: The corticosteroid-treated group revealed no significant difference compared to the control group concerning the pulp healing response (P > 0.05). Both Biodentine and MTA-treated specimens revealed significant differences with Ca(OH)2-treated specimens (P < 0.05) which displayed a superior positive effect of both MTA and Biodentine to Ca(OH)2 regarding all the parameters. CONCLUSIONS: Direct pulp capping technique whenever indicated in subjects treated with corticosteroid immunosuppressive drugs like prednisone performed well in aseptic conditions especially when capped with bioactive materials.

Delayed seropositivity is associated with lower levels of SARS-CoV-2 antibody levels in patients with mild to moderate COVID-19.

BACKGROUND: Patients with COVID-19 can develop a range of immune responses, including variations in the onset and magnitude of antibody formation. The aim of this study was to investigate whether SARS-CoV-2 antibody levels vary in patients with mild to moderate COVID-19 in relation to the onset (days) of their post-symptom seropositivity and to explore host factors that may affect antibody production METHODS: This was a prospective, multiple measurements study involving 92 PCR-confirmed patients with mild to moderate COVID-19. Antibody testing for anti-nucleocapsid (anti-NP) and spike proteins (anti-S) was performed using ELISA tests. Serum samples were collected over a period of 55 days from symptom onset of COVID-19 infection, and repeated as necessary until they turned positive. RESULTS: No significant differences were found between the positivity rates of anti-S or anti-NP regarding any clinical symptom (p > 0.05). The majority of patients who tested positive for anti-NP and anti-S showed early seropositivity (within 15 days of symptom onset) (75.9% for anti-NP and 82.6% for anti-S). Younger patients, those without chronic diseases, and non-healthcare workers had the highest percentage of seroconversion after day 35 post-symptom onset (p = 0.002, 0.028, and 0.036, respectively), while older patients and those with chronic diseases had earlier seropositivity and higher anti-NP levels (p = 0.003 and 0.06, respectively). Significantly higher anti-S ratios were found among older (p = 0.004), male (p = 0.015), and anemic patients (p = 0.02). A significant correlation was found between both antibodies (p = 0.001). At the end of the study, the cumulative seroconversion rate for both antibodies was almost 99%. CONCLUSIONS: Some COVID-19 patients may exhibit delayed and weak immune responses, while elderly, anemic patients and those with chronic diseases may show earlier and higher antibody responses.

Influence of selective immunosuppressive drug regimens on the healing of exposed dogs' dental pulp capped with a recent calcium silicate-based cement.

OBJECTIVES: In the clinical medicine, immunosuppressive drugs are used for an assortment of disorders, while their effect on the pulp healing is a controversial issue. This study evaluated the effect of different immunosuppressive drugs on the healing capacity of mechanically exposed dogs' dental pulps after direct pulp capping (DPC) with calcium silicate-based cement. MATERIALS AND METHODS: Twelve healthy male dogs were randomly allocated into four equal groups, 3 dogs each: group I allocated as a control group where no drugs were received; group П given prednisone (Pred); group III given a combination of Pred and cyclosporine A (CsA); and group IV given triple dose including Pred, CsA, and mycophenolate mofetil (MMF) for 45 days before the operative procedures and until the dogs were euthanized. In each dog, 16 class V cavities were prepared on the labial surfaces of anterior teeth. Following mechanical exposure, the pulps were capped with Biodentine, calcium silicate-based cement. The pulpal tissues response to Biodentine was assessed 65 days postoperatively. RESULTS: The pulp healing response was inferior in the Pred-CsA- and Pred-CsA-MMF-treated groups compared with the control and Pred-treated groups (P < 0.05). Non-significant difference was found between control and Pred-treated groups (P > 0.05). CONCLUSIONS: Within the limitation of this study, DPC with calcium silicate-based cement performed under strict aseptic condition for traumatically exposed dental pulp can be considered as a successful treatment option for those who receiving Pred immunosuppressive therapy. Meanwhile, DPC with those receiving a combination of Pred, CsA, and/or MMF immunosuppressive drug regimens demonstrated unfavorable results. CLINICAL RELEVANCE: Direct capping of mechanically exposed pulps with calcium silicate-based cement performed with special care for preventing infection considered a suitable strategic measure for preserving pulp vitality in patients receiving corticosteroid immunosuppressive drug.

The effects of COVID-19 pandemic and its related lockdown on female sexual function and reproductive health: An observational study in Egypt.

This retrospective observational online study was carried out to evaluate the effect of the COVID-19 pandemic and its related lockdown on female sexual functions and reproductive health. It included 409 sexually active females. The sexual function was assessed using the Female Sexual Function Index (FSFI). The reproductive life was assessed by a structured self-administered questionnaire modified from Egypt Demographic and Health Survey. The study revealed a significant decrease in the overall FSFI score during the pandemic lockdown compared to the pre-pandemic score (19.3 ± 6 vs. 21.3 ± 6.4, P<0.001). Below half (41.6 %) of women were using contraception methods during the pandemic, while 27.9% had stopped taking contraception during the pandemic, 30.6% (57/186) of the pregnant women only tended to get pregnant. So, the COVID-19 pandemic and its related lockdown were associated with an elevated risk for female sexual dysfunction and altered women's reproductive health quality. Heath system should therefore develop new methods to provide basic reproductive health service, family planning services, and to ameliorate the female sexual function during COVID-19 pandemic including consults with physicians, counsellors, and psychologists, as well as health education programs, either in person or virtually via telemedicine.

Ramadan fasting and liver diseases: A review with practice advices and recommendations.

Ramadan fasting is obligatory for Muslim healthy adults. However, there are many exemptions from fasting; including patients, whose diseases will be aggravated by fasting. Muslim patients with different liver diseases are frequently seen in the clinics discussing their intent to fast this month with their treating physicians. To answer our patients' inquiries about the expected benefits and/or risks of fasting and delivering them the best care, we carried out this review and we draw advices and recommendations based on the available evidence. A web-based search, combining multiple keywords representing different liver diseases with Ramadan fasting had been carried out. To answer the research question: Do adult Muslim patients with different liver diseases who fast the month of Ramadan have had a deleterious effect on their health in comparison to those who did not fast? Relevant publications were retrieved. No randomized controlled trials were focusing on Ramadan fasting and liver diseases in the filtered databases, eg Cochrane library. Consequently, non-filtered databases, eg PubMed, Google Scholar and Egyptian Knowledge Bank searched and full-text high-quality research articles were carefully analysed to draw recommendations. Other relevant publications with low quality of evidence like case studies and short communications were also reviewed to address practice advices. Although Ramadan fasting was found beneficial for patients with NAFLD, it was found deleterious to patients with Child B and C cirrhosis and patients with peptic ulcer. Patients with chronic hepatitis, Child A cirrhosis and those with non-complicated liver transplant can fast with prefasting assessment and strict follow up.

A study of the hepatoprotective effect of Plantago psyllium L. seed extract against Carbon tetrachloride induced hepatic injury in rats.

BACKGROUND: The liver is the main metabolic organ involved in disposal and detoxification of various molecules. Plantago psyllium L. seed has been reported to exert positive effects in some pathological conditions. The current study aims to assess the hepatoprotective effect of Plantago psyllium L. seed extract against carbon tetrachloride-induced hepatotoxicity. METHODS: Male albino Wistar rats were randomly divided into five groups of 10 rats each. Hepatotoxicity was induced by orally administered carbon tetrachloride (CCl4) for nine weeks with or without the different treatments which were utilized daily for the whole nine weeks. Serum and tissue samples were then withdrawn and different liver biomarkers were investigated. RESULTS: Treatment of rats with Psyllium seed ethanolic extract significantly alleviated the toxic effects of CCl4. This was evidenced by its ability to restore liver biomarkers levels. Moreover, treatment with Psyllium seed extract normalized levels of oxidative biomarkers such as lipid peroxidation, hepatic content of reduced glutathione and catalase activity, as well as the expression level of the inflammatory marker TNF-α. Histopathological examination reflected the protective effect of the extract on liver architecture and confirmed the observed biochemical data. CONCLUSIONS: The presented data demonstrates a potential hepatoprotective effect of Psyllium seed extract compared to the standard hepatoprotective drug silymarin. This effect can be attributed to the antioxidant and anti-inflammatory effects of Psyllium extract.

NEW PYRIDINE AND TRIAZOLOPYRIDINE DERIVATIVES: SYNTHESIS, ANTIMICROBIAL AND ANTIOXIDANT EVALUATION.

A novel series of pyridine and triazolopyridine derivatives have been synthesized (1-17) and characterized on the basis of their elemental analyses and spectral data. In vitro antibacterial, antifungal and antioxidant evaluation were carried out for most of the new products. Compounds 3, 5b, 6c, 6d and 13 showed promising growth inhibition against Candida albicans and Aspergillus niger comparable to fluconazole as a reference antifungal drug. Furthermore, the derivatives 5d, 6c, 6d and 9 showed higher scavenging activity (99.4, 97.2, 94.8 and 90%) than that of ascorbic acid (86.4%) towards the DPPH radicals.

Antiosteoporotic effect of Petroselinum crispum, Ocimum basilicum and Cichorium intybus L. in glucocorticoid-induced osteoporosis in rats.

BACKGROUND: Glucocorticoid-induced osteoporosis (GIO) is one of the serious side effects which have become the most common secondary osteoporosis. The purpose of this study is to evaluate the effect of aqueous extract of parsley, basil and chicory on glucocorticoid-induced osteoporosis in rats. METHODS: Fifty Female rats were divided into five groups and treated for 8 weeks as follow: group 1 served as control; group (2) subcutaneously injected with 0.1 mg/kg b. wt. dexamethasone dissolved in saline; group 3 received similar dose of dexamethasone together with aqueous parsley extract in a dose of 2 g/kg b. wt.; group 4 received similar dose of dexamethasone together with 400 mg/kg b. wt. aqueous basil extract and group 5 received similar dose of dexamethasone together with 100 mg/kg b. wt. aqueous chicory extract. RESULTS: The dexamethasone group showed a significant decrease in serum E2, Ca, P levels and significant decrease in total BMD, BMC and a significant increase in serum PTH, ALP and ACP. Bone TBARs was significantly increased while GSH, antioxidant enzymes were significantly decreased. These changes were attenuated by parsley, basil and chicory extracts in the group 3, 4 and 5 respectively. CONCLUSION: Aqueous extracts of parsley, basil and chicory showed bone protection against glucocorticoid-induced in rats. From our results, we concluded that chicory has a potent protective effect more than parsley and basil due to containing flavonoids and inulin.

Evaluation of circulating ADH and MIC-1 as diagnostic markers in Egyptian patients with pancreatic cancer.

BACKGROUND: Despite the incidence rate of pancreatic cancer (PC) is uncommon in developing countries, it is considered as one of the most lethal disease. Improving patients' survival requires diagnosis of the disease at early stage. Therefore, it is imperative to identify more specific and sensitive marker(s) to be used for early detection of PC. OBJECTIVES: Our aim is to evaluate the potential role of circulating ADH and MIC-1 to be used as diagnostic markers in Egyptian patients and assess their value either alone or combined with CA19-9 in early detection of PC. METHODS: Alcohol dehydrogenase (ADH), macrophage inhibitory cytokine (MIC-1) and CA19-9 were measured by ELISA in serum procured from PC patients (n = 50) versus normal subjects (n = 20). RESULTS: Our results demonstrate that the circulating levels of ADH, MIC-1 and CA19-9 in blood of PC were significantly higher than in healthy controls (HCs) (p < 0.001). The highest marker sensitivity observed at early stage was MIC-1 (90%) and specificity was ADH (83%). The level of all three markers was elevated significantly in early stage of PC in comparison to HCs. The addition of ADH and MIC-1 to CA19-9 significantly improved the efficacy of diagnosis (p = 0.023). CONCLUSION: Our data demonstrate that not only the combination of ADH and MIC-1 to CA19-9 can be used in early detection of PC but also can improve the overall quality of diagnosis of this lethal disease.

SYNTHESIS AND IN VITRO ANTIMICROBIAL ACTIVITY OF NOVEL SERIES OF 3,5-DIACETYLPYRIDINE COMPOUNDS.

Bis diacetylpyridine derivative (1) was prepared and reacted with different halo-compounds, namely: epichlorohydrine and dichloroethyl ethyl ether to give 2a,b, respectively, and reacted with morpholine and piperidine to afford Mannich products 3a,b, successively. Compound 4 was synthesized by reaction of 1 with potassium thiocyanate. Reaction of 4 with 4-chlorobenzaldehyde, glucose and phthalic or maleic anhydrides produced 5, 6 and 7a,b. Compound 1 reacted with 4-chlorobenzaldehyde to give bisanylmethylene derivative 8. Also some new compounds 9-11 were prepared from the reaction of compound 8 with nucleophiles, namely: hydrazine hydrate, thiosemicarbazide and hydroxylamine via Michael condensation reaction. On the other hand, compound 8 was reacted with cyclohexanone and cyclopentanone to give 12a,b. The structures of newly synthesized products have been deduced on the basis of elemental analysis and spectral data. Some synthesized compounds were screened for their antimicrobial evaluation. Among the assayed compounds, derivatives 3b and 12a showed the highest antimicrobial activities.

Synthesis, anticancer activity, docking and computational studies of new pyridyl-glycosyl hybrids and acyclic analogs.

New pyridine-O-glycosides and their acyclic nucleoside analogues were prepared by heterocyclization and glycosylation. The anticancer activity against HCT-116, HepG2 and MCF-7 human cancer cells and BJ-1 cell revealed that the galacto- and xylopyranosyl glycosides possessing 4-bromophenyl have superior cytotoxic activities against HepG2 cell while glycosides 7-9 resulted in superior cytotoxic activities regarding MCF-7 breast cell. In case of HCT-116 colorectal carcinoma cells, two products and the derived glycosides and acyclic analogues showed potent activities. The most potent compounds were investigated for their possible binding affinities to the active site of CDK2 enzyme via in silico molecular docking simulation in addition to computational studies. The results support the antiproliferative effect and elucidate the interactions of 3a and 8 with catalytic sites.

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Intermittent fasting and the liver: Focus on the Ramadan model.

Intermittent fasting (IF) is an intervention that involves not only dietary modifications but also behavioral changes with the main core being a period of fasting alternating with a period of controlled feeding. The duration of fasting differs from one regimen to another. Ramadan fasting (RF) is a religious fasting for Muslims, it lasts for only one month every one lunar year. In this model of fasting, observers abstain from food and water for a period that extends from dawn to sunset. The period of daily fasting is variable (12-18 hours) as Ramadan rotates in all seasons of the year. Consequently, longer duration of daily fasting is observed during the summer. In fact, RF is a peculiar type of IF. It is a dry IF as no water is allowed during the fasting hours, also there are no calorie restrictions during feeding hours, and the mealtime is exclusively nighttime. These three variables of the RF model are believed to have a variable impact on different liver diseases. RF was evaluated by different observational and interventional studies among patients with non-alcoholic fatty liver disease and it was associated with improvements in anthropometric measures, metabolic profile, and liver biochemistry regardless of the calorie restriction among lean and obese patients. The situation is rather different for patients with liver cirrhosis. RF was associated with adverse events among patients with liver cirrhosis irrespective of the underlying etiology of cirrhosis. Cirrhotic patients developed new ascites, ascites were increased, had higher serum bilirubin levels after Ramadan, and frequently developed hepatic encephalopathy and acute upper gastrointestinal bleeding. These complications were higher among patients with Child class B and C cirrhosis, and some fatalities occurred due to fasting. Liver transplant recipients as a special group of patients, are vulnerable to dehydration, fluctuation in blood immunosuppressive levels, likelihood of deterioration and hence observing RF without special precautions could represent a real danger for them. Patients with Gilbert syndrome can safely observe RF despite the minor elevations in serum bilirubin reported during the early days of fasting.

Exploring Knowledge, Safety Practices, and Anxiety Level among Women of Reproductive Age During COVID-19 Outbreak: A Cross-Sectional Study.

Background: The global outbreak of coronavirus disease 2019 (COVID-19) and its consequences compromise the health of Women of Reproductive Age (WRA). The aim of this study was to assess the level of knowledge, safety practices, and anxiety levels among WRA during COVID-19 outbreaks. Materials and Methods: A cross-sectional, correlational design was used to recruit a convenience sample of 453 WRA in Saudi Arabia. Data were collected using an electronic self-administered questionnaire of Spielberger state-trait anxiety and an adapted authors-developed knowledge and practices scale using an extensive literature review. Data were collected between September and December 2020 targeting all women in the country. Pearson correlation coefficient has been used to test correlation utilizing the Statistical Package for the Social Sciences (SPSS) 25. Results: The mean score of anxiety was 46.0 (13.40). Women have a high mean score of knowledge (24.50, standard deviation (SD) = 3.40) while having a low mean score of practices (19.70, SD = 3.10) indicating inappropriate practices. A significant difference was found in anxiety (t479 = 2.52, p = .012) and knowledge (t479 = -1.98, p = .048) between pregnant and non-pregnant women, while no statistically significant difference was found in relation to practices. The mean score of anxiety was higher among pregnant women than non-pregnant women, while a slightly higher mean score of knowledge was observed for non-pregnant women compared to pregnant ones. Conclusions: Although women had good knowledge about safety precautions, their practices did not indicate that. There is a need to educate women about safety practices and interventions that buffer their anxiety levels.

The Pathogenic Role of Oxidative Stress, Cytokine Expression, and Impaired Hematological Indices in Diabetic Cardiovascular Diseases.

A simultaneous increase in the prevalence of diabetes mellitus (DM), a risk factor for cardiovascular diseases (CVDs), has contributed to the escalation of CVD related mortalities. To date, oxidative stress and inflammation are increasingly recognized as significant drivers of cardiovascular complications in patients with diabetes. Therefore, this study aims to explore the correlation between oxidative stress, inflammation, and hematological indices in diabetic patients with CVDs. Patients were allocated into five groups: healthy controls; nondiabetic patients with myocardial infarction; diabetic patients with myocardial infarction; nondiabetic patients with heart failure; and diabetic patients with heart failure. The results revealed that the malondialdehyde levels were increased; whereas superoxide dismutase enzyme activities were markedly reduced in all CVD groups compared with those of healthy controls. Although the mRNA expression levels of interleukin (IL)-6, IL-18, and IL-38 were significantly increased, those of the anti-inflammatory cytokine, IL-35, have been reduced in all CVD groups compared with healthy controls. Regarding hematological indices, hematocrit, red blood cell distribution width, mean platelet (PLT) volume, plateletcrit, PLT distribution width, leukocyte count, and PLT-to-lymphocyte and neutrophil-to-lymphocyte ratios were markedly increased in the diabetic and nondiabetic CVD groups compared with those of the healthy controls. Oxidative stress and cytokine biomarkers may play a significant role in the complications of diabetic cardiomyopathy. Moreover, hematological indices are particularly sensitive to systemic inflammatory changes and are novel markers for the early detection of diabetic cardiomyopathy.

Naringin and naringenin counteract taxol-induced liver injury in Wistar rats via suppression of oxidative stress, apoptosis and inflammation.

This research aimed to evaluate the preventing effects of naringin, naringenin, and their combination on liver injury induced by Taxol (paclitaxel) in Wistar rats. Male Wistar rats received 2 mg/kg Taxol intraperitoneal injections twice weekly on the second and fifth days of each week for 6 weeks. During the same period as Taxol administration, rats were given naringin, naringenin, or a combination of the two (10 mg/kg b.wt) every other day. Treatment with naringin and/or naringenin reduced the abnormally high serum levels of total bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma-glutamyl transferase in Taxol-treated rats. It also significantly increased the level of serum albumin, indicating an improvement in the liver. The perturbed histological liver changes were markedly improved due to the naringin and/or naringenin treatment in Taxol-administered rats. Additionally, the treatments reduced high hepatic lipid peroxidation and increased liver glutathione content as well as the activities of superoxide dismutase and glutathione peroxidase. Furthermore, the treatments reduced the levels of alpha-fetoprotein and caspase-3, a pro-apoptotic mediator. The naringin and naringenin mixture appeared more effective in improving organ function and structural integrity. In conclusion, naringin and naringenin are suggested to employ their hepatoprotective benefits via boosting the body's antioxidant defense system, reducing inflammation, and suppressing apoptosis.

Rutin and Hesperidin Alleviate Paclitaxel-Induced Nephrocardiotoxicity in Wistar Rats via Suppressing the Oxidative Stress and Enhancing the Antioxidant Defense Mechanisms.

Paclitaxel is a primary chemotherapy agent that displays antitumor activity against a variety of solid tumors. However, the clinical effectiveness of the drug is hampered by its nephrotoxic and cardiotoxic side effects. Thus, this investigation aimed at assessing the protective effects of rutin, hesperidin, and their combination to alleviate nephrotoxicity caused by paclitaxel (Taxol), cardiotoxicity in male Wistar rats, as well as oxidative stress. Rutin (10 mg/kg body weight), hesperidin (10 mg/kg body weight), and their mixture were given orally every other day for six weeks. Rats received intraperitoneal injections of paclitaxel twice weekly, on the second and fifth days of the week, at a dose of 2 mg/kg body weight. In paclitaxel-treated rats, the treatment of rutin and hesperidin decreased the elevated serum levels of creatinine, urea, and uric acid, indicating a recovery of kidney functions. The cardiac dysfunction in paclitaxel-treated rats that got rutin and hesperidin treatment also diminished, as shown by a substantial reduction in elevated CK-MB and LDH activity. Following paclitaxel administration, the severity of the kidney and the heart's histopathological findings and lesion scores were markedly decreased by rutin and hesperidin administration. Moreover, these treatments significantly reduced renal and cardiac lipid peroxidation while markedly increased GSH content and SOD and GPx activities. Thus, paclitaxel likely induces toxicity in the kidney and the heart by producing oxidative stress. The treatments likely countered renal and cardiac dysfunction and histopathological changes by suppressing oxidative stress and augmenting the antioxidant defenses. Rutin and hesperidin combination was most efficacious in rescuing renal and cardiac function as well as histological integrity in paclitaxel-administered rats.

Rutin and Hesperidin Revoke the Hepatotoxicity Induced by Paclitaxel in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities.

Paclitaxel, one of the most effective chemotherapeutic drugs, is used to treat various cancers but it is exceedingly toxic when used long-term and can harm the liver. This study aimed to see if rutin, hesperidin, and their combination could protect male Wistar rats against paclitaxel (Taxol)-induced hepatotoxicity. Adult male Wistar rats were subdivided into 5 groups (each of six rats). The normal group was orally given the equivalent volume of vehicles for 6 weeks. The paclitaxel-administered control group received intraperitoneal injection of paclitaxel at a dose of 2 mg/Kg body weight twice a week for 6 weeks. Treated paclitaxel-administered groups were given paclitaxel similar to the paclitaxel-administered control group together with oral supplementation of rutin, hesperidin, and their combination at a dose of 10 mg/Kg body weight every other day for 6 weeks. The treatment of paclitaxel-administered rats with rutin and hesperidin significantly reduced paclitaxel-induced increases in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transferase activities as well as total bilirubin level and liver lipid peroxidation. However, the levels of serum albumin, liver glutathione content, and the activities of liver superoxide dismutase and glutathione peroxidase increased. Furthermore, paclitaxel-induced harmful hepatic histological changes (central vein and portal area blood vessel congestion, fatty changes, and moderate necrotic changes with focal nuclear pyknosis, focal mononuclear infiltration, and Kupffer cell proliferation) were remarkably enhanced by rutin and hesperidin treatments. Moreover, the elevated hepatic proapoptotic mediator (caspase-3) and pro-inflammatory cytokine (tumor necrosis factor-α) expressions were decreased by the three treatments in paclitaxel-administered rats. The cotreatment with rutin and hesperidin was the most effective in restoring the majority of liver function and histological integrity. Therefore, rutin, hesperidin, and their combination may exert hepatic protective effects in paclitaxel-administered rats by improving antioxidant defenses and inhibiting inflammation and apoptosis.

LC-MS based serum metabolomics for identification of hepatocellular carcinoma biomarkers in Egyptian cohort.

Although hepatocellular carcinoma (HCC) has been subjected to continuous investigation and its symptoms are well-known, early stage diagnosis of this disease remains difficult and the survival rate after diagnosis is typically very low (3-5%). Early and accurate detection of metabolic changes in the sera of patients with liver cirrhosis can help improve the prognosis of HCC and lead to a better understanding of its mechanism at the molecular level, thus providing patients with in-time treatment of the disease. In this study, we compared metabolite levels in sera of 40 HCC patients and 49 cirrhosis patients from Egypt by using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from cirrhotic controls are selected by statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. The identities of some of the putative identifications are verified by comparing their MS/MS fragmentation patterns and retention times with those from authentic compounds. Finally, the serum samples are reanalyzed for quantitation of selected metabolites as candidate biomarkers of HCC. This quantitation was performed using isotope dilution by selected reaction monitoring (SRM) on a triple quadrupole linear ion trap (QqQLIT) coupled to UPLC. Statistical analysis of the UPLC-QTOF data identified 274 monoisotopic ion masses with statistically significant differences in ion intensities between HCC cases and cirrhotic controls. Putative identifications were obtained for 158 ions by mass based search against databases. We verified the identities of selected putative identifications including glycholic acid (GCA), glycodeoxycholic acid (GDCA), 3ß, 6ß-dihydroxy-5ß-cholan-24-oic acid, oleoyl carnitine, and Phe-Phe. SRM-based quantitation confirmed significant differences between HCC and cirrhotic controls in metabolite levels of bile acid metabolites, long chain carnitines and small peptide. Our study provides useful insight into appropriate experimental design and computational methods for serum biomarker discovery using LC-MS/MS based metabolomics. This study has led to the identification of candidate biomarkers with significant changes in metabolite levels between HCC cases and cirrhotic controls. This is the first MS-based metabolic biomarker discovery study on Egyptian subjects that led to the identification of candidate metabolites that discriminate early stage HCC from patients with liver cirrhosis.