Diet, lifestyle factors, comorbidities, and hepatocellular carcinoma risk in a middle eastern country: a case-control study.

BACKGROUND: Hepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in the Gulf Cooperation Council countries specifically Kuwait. Therefore, this case-control study sought to examine the risk factors associated with HCC in Kuwait. METHODS: Fifty-three histopathologically confirmed HCC cases were recruited from the Kuwait Cancer Control Center Registry. One hundred ninety-six controls (1:4 ratio) were selected from medical and/ or surgical outpatient's clinics at all six public hospitals of Kuwait. A structured questionnaire was used to collect the data both from cases and controls through face-to-face interviews. A multivariable logistic regression model was fitted to the case-control data. Adjusted odds ratios (ORadj) and their 95% confidence intervals (CI) were computed using the parameters' estimates of the final model and used for interpretation of the model. RESULTS: The HCC cases compared with the controls were 41.6 times more likely to have had the history of non-alcoholic fatty liver disease (NAFLD) (ORadj = 41.6; 95% CI: 8.9-193.5; p < 0.001). The cases compared with the controls were more likely to have reported the history of heavy alcohol drinking (ORadj = 14.2; 95% CI: 1.2-173.4; p = 0.038). Furthermore, compared with the controls, the HCC cases tended to frequently consume milk and/or milk substitutes (≥ 3 glass/ week) (ORadj = 7.2; 95% CI: 1.2-43.4). Conversely however, there was a significant protective effect if the participants reportedly have had regularly used olive oil in their routine diet as a source of fat (ORadj = 0.17; 95% CI: 0.04-0.80) or regularly used non-steroid anti-inflammatory drugs (NSAIDs) (ORadj = 0.20; 95% CI: 0.05-0.71). CONCLUSIONS: This study showed that heavy alcohol consumption, NAFLD history, and excessive consumption of milk/ milk substitutes were associated with a significantly increased HCC risk. Conversely however, regular use of olive oil in the diet as a source of fat or regular use of NSAIDs had a significantly protective effect against HCC risk. Adapting healthy dietary habits and preventing/ treating NAFLD may minimize the HCC risk. Future research with a larger sample size may contemplate validating the results of this study and unraveling additional risk factors contributing to HCC risk. The resultant data may help design and implement evidence-based educational programs for the prevention of HCC in this and other similar settings.

Correction: Abbas et al. Bioactive Compounds, Antioxidant, Anti-Inflammatory, Anti-Cancer, and Toxicity Assessment of Tribulus terrestris-In Vitro and In Vivo Studies. Antioxidants 2022, 11, 1160.

In the original publication [...].

Antenatal Depression and its Associated Factors: Findings from Kuwait Birth Cohort Study.

BACKGROUND: Pregnant and postpartum women are at high risk of depression due to hormonal and biological changes. Antenatal depression is understudied compared to postpartum depression and its predictors remain highly controversial. AIM: To estimate the prevalence of depressive symptoms during pregnancy and investigate factors associated with this condition including vitamin D, folate and Vitamin B12 among participants in the Kuwait Birth Study. METHODS: Data collection occurred as part of the Kuwait Birth Cohort Study in which pregnant women were recruited in the second and third trimester during antenatal care visits. Data on antenatal depression were collected using the Edinburgh Postnatal Depression Scale (EPDS), considering a score of ≥ 13 as an indicator of depression. Logistic regression was used to investigate factors associated with depressive symptoms in pregnant women. RESULTS: Of 1108 participants in the Kuwait Birth Cohort study, 1070(96.6%) completed the EPDS. The prevalence of depressive symptoms was 21.03%(95%CI:18.62-23.59%) and 17.85%(95%CI:15.60-20.28%) as indicated by an EPDS ≥ 13 and EPDS ≥ 14 respectively. In the multivariable analysis, passive smoking at home, experiencing stressful life events during pregnancy, and a lower level of vitamin B12 were identified as predisposing factors. Conversely, having desire for the pregnancy and consumption of fruits and vegetables were inversely associated with depressive symptoms. CONCLUSION: Approximately, one fifth of pregnant women had depressive symptoms indicating the need to implement screening program for depression in pregnant women, a measure not systematically implemented in Kuwait. Specifically, screening efforts should focus on pregnant women with unintended pregnancies, exposure to passive smoking at home, and recent stressful live events.

Prevalence of and factors associated with multimorbidity among adults in Kuwait.

BACKGROUND: This cross-sectional study aimed to assess the prevalence of morbidity i.e., one morbidity and multimorbidity (≥ 2 morbid conditions) among adults in Kuwait and to examine the sociodemographic and lifestyle factors associated with morbidity as a multinomial outcome in the study population. METHODS: The data were collected from January 26, 2021, to February 3, 2021, using an electronic questionnaire, which was distributed on social media platforms. The consent form was attached with the questionnaire and the participants were requested to sign the consent form before completing the questionnaire. The prevalences (%) of each morbidity and multimorbidity were computed. Multivariable polychotomous logistic regression analysis was used to evaluate the association between the demographic and lifestyle factors with morbidity as a multinomial outcome. RESULTS: Of 3572 respondents included, 89% were Kuwaiti, 78.3% females and 66% were 21- 40 years old. The prevalence of multimorbidity and one morbidity respectively was 27.4% and 29.7%. The prevalence of multimorbidity with two, three, four or five ill-health conditions were 14.3%, 7.4%, 3.5%, and 1.2%, respectively. A higher prevalence of multimorbidity was among respondents over 60 years of age (71%) and Kuwaiti nationals (28.9%). The final multivariable polychotomous logistic regression model revealed that age, sex, nativity, sedentary lifestyle, smoking, and alcohol drinking were significantly (p < 0.05) associated with multimorbidity. However, age and alcohol drinking were significant (p < 0.05) predictors of one morbidity. CONCLUSION: This study provides evidence that multimorbidity is more prevalent among the elderly, females, and Kuwaiti nationals. Sedentary behaviour, smoking and alcohol consumption were significantly and independently associated with multimorbidity. These findings highlight the burden of multimorbidity and should be considered in the development of future prevention programs.

Exposure to household secondhand tobacco smoke and the odds of developing atopic dermatitis among adolescents: A causal mediation analysis.

INTRODUCTION: Exposure to household secondhand tobacco smoke (SHS) among adolescents has been shown to be associated with atopic dermatitis, and affects disproportionality females. However, the mechanisms underlying this link are uncertain. This study sought to identify modifiable factors that mediate the relationship between household SHS exposure and atopic dermatitis among adolescents. METHODS: During October 2015, a cross-sectional study was conducted using the ISAAC questionnaire for data collection from adolescents enrolled in nine high schools of Hawalli - one of the six governorates of Kuwait. Data were collected on sociodemographic characteristics, self-reported tobacco smoking among adolescents, household SHS exposure (≥1 smokers at home vs none), self-reported asthma and atopic dermatitis. For causal mediation analysis an inverse odds-weighting approach was used. RESULTS: Of 746 participants, 74.8% were Kuwaiti, 50.1% were female, 12.4% were regular daily smokers and 54.1% had household SHS exposure, which was more common among Kuwaiti (79.6%) than non-Kuwaiti (20.4%) adolescents. The prevalences of self-reported asthma and atopic dermatitis were 20.6% and 14.9%, respectively. After adjusting for the pre-exposure covariates (i.e. sex and nativity), household SHS exposure had a significant (p=0.043) total effect, non-significant (p=0.133) natural direct effect, and marginally insignificant (p=0.058) natural indirect effect, which were jointly mediated by asthma status and adolescent's self-reported smoking status, with a proportion of mediated risk to atopic dermatitis of 29.6%. CONCLUSIONS: Asthma and self-tobacco smoking among adolescents not only directly affected but also mediated household SHS exposure effect on atopic dermatitis risk. Voluntarily adopting a smoke-free home rule may minimize household SHS exposure, reduce the odds of developing asthma, and deter the initiation of tobacco smoking among adolescents. Such an effort will likely mitigate the atopic dermatitis risk among adolescents in this and other similar settings. If implemented, future studies may contemplate evaluating the impact of such intervention.

Neonatal Hearing Screening Programme And Challenges Faced By The Developing Country: A Tertiary Care Hospital Experience.

OBJECTIVE: To screen new-borns to diagnose any hearing impairment early. METHODS: The prospective, cross-sectionalstudy was conducted at the Department of Otorhinolaryngology, Head and Neck Surgery Liaquat National Hospital, Karachi, from November 1, 2020, to April 30, 2021, and new- borns of either gender aged >12h born via spontaneous vaginal delivery, induced labour, and Caesarean section. A predesigned questionnaire was used to collect detailed case history, including gestational age, duration of labour, and other prenatal, natal, and postnatal risk factors. Otoacoustic emission test was performed, and infants referred twice were scheduled for complete diagnostic evaluation and brainstem evoked response audiometry. Data was analysed using SPSS 23. RESULTS: Of the 267 neonates, 249(93.3%) passed the first screening. Of the remaining 18(6.7%) neonates, 8(44.4%) passed the second screening, while 10(55.5%) were asked to come for a follow-up after three weeks. Of them, 3(30%) returned for check-up, while 7(70%) did not show up. CONCLUSIONS: Neonatal risk factors associated with hearing loss need to be identified, and a comprehensive hearing screening programme is required for neonates.

Disparities in oesophageal cancer risk by age, sex, and nativity in Kuwait:1980-2019.

BACKGROUND: This cross-sectional cohort study assessed the inequalities in oesophageal carcinoma risk by age, sex and nativity in Kuwait: 1980-2019. METHODS: Using oesophageal cancer incidence data from the Kuwait National Cancer Registry, relevant Kuwaiti population data and World Standard Population as a reference, age-standardized incidence rates (ASIR) (per 100,000 person-years) overall and by subcohorts were computed. The incident oesophageal cancer cases count was overdispersed with excessive structural zeros, therefore, it was analyzed using multivariable zero-inflated negative binomial (ZINB) model. RESULTS: Overall ASIR of oesophageal cancer was 10.51 (95% CI:  6.62-14.41). The multivariable ZINB model showed that compared with the younger age category (< 30 years), the individuals in higher age groups showed a significant (p < 0.001) increasing tendency to develop the oesophageal cancer.  Furthermore, compared with the non-Kuwaiti residents, the Kuwaiti nationals were significantly (p < 0.001) more likely to develop oesophageal cancer during the study period. Moreover, compared with 1980-84 period, ASIRs steadily and significantly  (p < 0.005) declined in subsequent periods till 2015-19. CONCLUSIONS: A high incidence of oesophageal cancer was recorded in Kuwait, which consistently declined from 1980 to 2019. Older adults (aged ≥ 60 years) and, Kuwaiti nationals were at high risk of oesophageal cancer. Focused educational intervention may minimize oesophageal cancer incidence in high-risk groups in this and other similar settings. Future studies may contemplate to evaluate such an intervention.

Deficiency of the RNA-binding protein ELAVL1/HuR leads to the failure of endogenous and exogenous neuroprotection of retinal ganglion cells.

Introduction: ELAVL1/HuR is a keystone regulator of gene expression at the posttranscriptional level, including stress response and homeostasis maintenance. The aim of this study was to evaluate the impact of hur silencing on the age-related degeneration of retinal ganglion cells (RGC), which potentially describes the efficiency of endogenous neuroprotection mechanisms, as well as to assess the exogenous neuroprotection capacity of hur-silenced RGC in the rat glaucoma model. Methods: The study consisted of in vitro and in vivo approaches. In vitro, we used rat B-35 cells to investigate, whether AAV-shRNA-HuR delivery affects survival and oxidative stress markers under temperature and excitotoxic insults. In vivo approach consisted of two different settings. In first one, 35 eight-week-old rats received intravitreal injection of AAV-shRNA-HuR or AAV-shRNA scramble control. Animals underwent electroretinography tests and were sacrificed 2, 4 or 6 months after injection. Retinas and optic nerves were collected and processed for immunostainings, electron microscopy and stereology. For the second approach, animals received similar gene constructs. To induce chronic glaucoma, 8 weeks after AAV injection, unilateral episcleral vein cauterization was performed. Animals from each group received intravitreal injection of metallothionein II. Animals underwent electroretinography tests and were sacrificed 8 weeks later. Retinas and optic nerves were collected and processed for immunostainings, electron microscopy and stereology. Results: Silencing of hur induced apoptosis and increased oxidative stress markers in B-35 cells. Additionally, shRNA treatment impaired the cellular stress response to temperature and excitotoxic insults. In vivo, RGC count was decreased by 39% in shRNA-HuR group 6 months after injection, when compared to shRNA scramble control group. In neuroprotection study, the average loss of RGCs was 35% in animals with glaucoma treated with metallothionein and shRNA-HuR and 11.4% in animals with glaucoma treated with metallothionein and the scramble control shRNA. An alteration in HuR cellular content resulted in diminished photopic negative responses in the electroretinogram. Conclusions: Based on our findings, we conclude that HuR is essential for the survival and efficient neuroprotection of RGC and that the induced alteration in HuR content accelerates both the age-related and glaucoma-induced decline in RGC number and function, further confirming HuR's key role in maintaining cell homeostasis and its possible involvement in the pathogenesis of glaucoma.

Antioxidant Effect of Ocimum basilicum Essential Oil and Its Effect on Cooking Qualities of Supplemented Chicken Nuggets.

A commonly observed chicken meat issue is its lipid oxidation that leads to deterioration of its organoleptic and nutritional properties and its further-processed products. Basil (Ocimum basilicum L.) is one of the traditional culinary herbs exhibiting food preservation properties. The current study investigated the essential oil composition, antioxidant activity and in vitro cytotoxic capacity of the essential oil of basil indigenous to Pakistan. GC-MS analysis of the essential oil revealed the presence of 59 compounds that constituted 98.6% of the essential oil. O. basilicum essential oil (OB-EO) exhibited excellent antioxidant activity, i.e., IC50 5.92 ± 0.15 µg/mL as assayed by the DPPH assay, 23.4 ± 0.02 µmoL Fe/g by FRAP, and 14.6 ± 0.59% inhibition by H2O2. The brine shrimp lethality assay identified an average mortality of ~18% with OB-EO at 10-1000 µg/mL, while that of the same concentration range of the standard drug (etoposide) was 72%. OB-EO was found to be non-toxic to HeLa and PC-3 cell lines. TBARS contents were significantly decreased with increase of OB-EO in chicken nuggets. The lowest TBARS contents were recorded in nuggets supplemented with 0.3% OB-EO, whereas the highest overall acceptability score was marked to the treatments carrying 0.2% OB-EO. The results suggest OB-EO as a promising carrier of bioactive compounds with a broad range of food preservation properties, and which has a sensory acceptability threshold level for chicken nuggets falling between 0.2-0.3% supplementation. Future research must investigate the antibacterial impact of OB-EO on meat products preserved with natural rather than synthetic preservatives.

Comparison of Endoscopic Versus Microscopic Tympanoplasty.

Introduction: Tympanoplasty is a common surgery for chronic otitis media and has conventionally been performed with a microscope for decades. The trend of endoscopic minimally invasive surgeries has been increasing worldwide for the last few decades. Few studies have discussed the outcomes of tympanoplasty with microscope and tympanoplasty with endoscope . This study aims to compare results of tympanoplasty done with microscope vs endoscope in terms of graft take rate and improvement in conductive hearing loss. Materials and Methods: We did a retrospective review of 120 patients (54 male and 66 female) who underwent Type I tympanoplasty at Liaquat National Postgraduate Medical Center from January 2019 to January 2020. We included 60 patients who underwent tympanoplasty with microscope and 60 patients who underwent tympanoplasty with endoscope. Postoperative graft uptake and hearing improvement were studied. Results: Overall mean preoperative hearing loss was 30.24 (±9.61) dB as compared to mean postoperative hearing loss, which was reduced to 19.36 ( ±8.54) dB, and the difference was significant (P-value <0.001. No statistically significant difference was found for air-bone gap closure between the two groups (P-value 0.78). Out of 120 patients, overall successful graft uptake was seen in 109 (90.8%). In tympanoplasty with microscope, graft take was 90.0%, compared to 91.6% in endoscope group. There was no significant difference in graft take in the two groups. Conclusions: The tympanoplasty with endoscope is comparable to tympanoplasty with microscope in terms of graft uptake and hearing improvement.

Bioactive Compounds, Antioxidant, Anti-Inflammatory, Anti-Cancer, and Toxicity Assessment of Tribulus terrestris-In Vitro and In Vivo Studies.

Tribulus terrestris L. belongs to the family Zygophyllaceae and integral part of various ancient medicinal systems including Chinese, Indian, and European to combat various health ailments. The aim of the present study was to assess the phytochemical constituents, in vitro antioxidant activity using DPPH, FRAP, and H2O2 assays, in vitro anticancer activity using MTT assay, and in vitro and in vivo anti-inflammatory properties of T. terrestris. The acute and sub-acute toxicity of extracts exhibiting most biological potential was examined using murine models. Liquid-liquid partitioning followed by RP-HPLC sub-fraction of crude extract was performed. After that, ESI-MS/MS analysis was done for the timid identification of bioactive metabolites responsible for bioactivities of sub-fractions and HPLC analysis to quantify the compounds using external standards. Among all extracts, T. terrestris methanol extract was noted to hold maximum phenolic (341.3 mg GAE/g) and flavonoid (209 mg QE/g) contents, antioxidant activity in DPPH (IC50 71.4 µg/mL), FRAP (35.3 mmol/g), and H2O2 (65.3% inhibition) assays, anti-inflammatory activities in vitro at 400 µg/mL (heat-induced hemolysis, % inhibition 68.5; egg albumin denaturation, % inhibition 75.6%; serum albumin denaturation, % inhibition 80.2), and in vivo at 200 mg/kg (carrageenan-induced paw edema, % inhibition 69.3%; formaldehyde-induced paw edema, % inhibition 71.3%) and anticancer activity against breast cancer cell (MCF-7) proliferation (IC50 74.1 µg/mL). Acute and sub-acute toxicity studies recorded with no change in body weight, behavior, hematological, serum, and histopathological parameters in treated rats with T. terrestris methanol extracts when compared to control group. Fraction B obtained through liquid-liquid partitioning resulted in more bioactive potential as compared to the parent methanol extract. RP-HPLC analysis of fraction B resulted with four sub-fractions (TBTMF1-TBTMF4), wherein TBTMF3 delineated notable bioactive capabilities as compared to other fractions and parent methanol extract. ESI-MS/MS analysis of TBTMF3 resulted with tentative identification of myricetin, rutin, liquitrigenin, physcion, and protodioscin. It can be stated that T. terrestris is a potential bearing herb and findings of current study further verify the claims made in ancient medicinal systems. However, after investigation of each identified compound, it must be considered for drug discovery.

Toxicity, Antioxidant Activity, and Phytochemicals of Basil (Ocimum basilicum L.) Leaves Cultivated in Southern Punjab, Pakistan.

Basil (Ocimum basilicum L.) is one of the most common aromatic herbs, a rich source of bioactive compounds, and is used extensively to add aroma and flavor to food. The leaves, both in fresh and dried form, are used as a culinary ingredient in different cultures. O. basilicum is also famous for its therapeutic potential and preservation effects. The present study investigated the cytotoxicity of basil at three different growth stages (GS), i.e., GS-1 (58 days of growth), GS-2 (69 days of growth), and GS-3 (93 days of growth) using the brine shrimp lethality assay. The results revealed that cytotoxicity was influenced by GS and the concentration of extracts. Aqueous extracts of basil at a concentration of 10 to 1000 µg/mL did not show notable toxicity. The lowest mortality rate, i.e., 8.9%, was recorded for GS-2 at the highest tested dose of basil extracts. The mortality rate at GS-1, GS-2, and GS-3 was found to be 26.7 ± 3.34%, 8.91 ± 0.10%, and 16.7 ± 0.34%, respectively, at 1000 µg/mL. GS-2 basil powder with the lowest toxicological risk was extracted with different solvents, viz., n-hexane, dichloromethane, ethanol, and water. The highest concentration of plant secondary metabolites including total phenolic acid, flavonoids, and tannin content was observed in ethanol extracts. Ethanol extracts also exhibited the highest antioxidant activity in DPPH, FRAP and H2O2 assays. LC-ESI-MS/MS analysis presented ethanol extracts of basil as a promising source of known health-promoting and therapeutic compounds such as rosmarinic acid, ellagic acid, catechin, liquiritigenin, and umbelliferone. The results suggest basil, a culinary ingredient, as a potential source of bioactive compounds which may offer an array of health promoting and therapeutic properties.

Antiinflammatory and Anticancer Properties of Grewia asiatica Crude Extracts and Fractions: A Bioassay-Guided Approach.

The study was an extension of our earlier work on antiinflammatory and anticancer properties of G. asiatica fruit. We aimed to develop a bioassay guided multistep purification technique for producing bioactive fractions of G. asiatica crude extracts. Dried fruit powder was sequentially fractionated with 100% dichloromethane, 100% methanol (MeOH), and 50% MeOH. Active extracts were subjected to liquid-liquid partitioning followed by subfractionation using RP-HPLC. Antioxidant, antiinflammatory, and anticancer activities of the fruit extracts, and their potent fractions were evaluated in vitro, while identification of compounds from the bioactive fractions was performed by ESI-MS/MS analysis. The amount of the identified compounds present was confirmed using external standards adopting a simple, accurate, and rapid analytical HPLC method. The results showed that 100% and 50% MeOH extracts possessed bioactivity; one of which (the 50% MeOH extract) displayed potent activity in all in vitro bioassays. MeOH extract (50%) derived fraction C and hydroalcoholic fraction 5 (GAHAF5) were observed to possess higher antioxidant, antiinflammatory, and in vitro anticancer activity. IC50 of GAHAF5 against MCF-7, HEp-2, and NCI-H522 cancer cells was recorded as 26.2, 51.4, and 63 µg/mL, respectively. ESI-MS/MS and HPLC analysis identified catechin, chlorogenic acid, caffeic acid, and morin as potential bioactive compounds in the GAHAF5 fraction with concentrations of 1230, 491, 957, and 130 µg/g, respectively. The findings indicated that G. asiatica bioactive fractions possessed antiinflammatory activity in vitro and were cytotoxic against breast cancer, lung cancer, and laryngeal cancer cell lines.

Phytochemical Profile, Biological Properties, and Food Applications of the Medicinal Plant Syzygium cumini.

Syzygium cumini, locally known as Jamun in Asia, is a fruit-bearing crop belonging to the Myrtaceae family. This study aims to summarize the most recent literature related to botany, traditional applications, phytochemical ingredients, pharmacological activities, nutrition, and potential food applications of S. cumini. Traditionally, S. cumini has been utilized to combat diabetes and dysentery, and it is given to females with a history of abortions. Anatomical parts of S. cumini exhibit therapeutic potentials including antioxidant, anti-inflammatory, analgesic, antipyretic, antimalarial, anticancer, and antidiabetic activities attributed to the presence of various primary and secondary metabolites such as carbohydrates, proteins, amino acids, alkaloids, flavonoids (i.e., quercetin, myricetin, kaempferol), phenolic acids (gallic acid, caffeic acid, ellagic acid) and anthocyanins (delphinidin-3,5-O-diglucoside, petunidin-3,5-O-diglucoside, malvidin-3,5-O-diglucoside). Different fruit parts of S. cumini have been employed to enhance the nutritional and overall quality of jams, jellies, wines, and fermented products. Today, S. cumini is also used in edible films. So, we believe that S. cumini's anatomical parts, extracts, and isolated compounds can be used in the food industry with applications in food packaging and as food additives. Future research should focus on the isolation and purification of compounds from S. cumini to treat various disorders. More importantly, clinical trials are required to develop low-cost medications with a low therapeutic index.

The Chemical Composition and Health-Promoting Effects of the Grewia Species-A Systematic Review and Meta-Analysis.

Globally grown and organoleptically appreciated Grewia species are known as sources of bioactive compounds that avert the risk of communicable and non-communicable diseases. Therefore, in recent years, the genus Grewia has attracted increasing scientific attention. This is the first systematic review which focusses primarily on the nutritional composition, phytochemical profile, pharmacological properties, and disease preventative role of Grewia species. The literature published from 1975 to 2021 was searched to retrieve relevant articles from databases such as Google Scholar, Scopus, PubMed, and Web of Science. Two independent reviewers carried out the screening, selection of articles, and data extraction. Of 815 references, 56 met our inclusion criteria. G. asiatica and G. optiva were the most frequently studied species. We found 167 chemical compounds from 12 Grewia species, allocated to 21 categories. Flavonoids represented 41.31% of the reported bioactive compounds, followed by protein and amino acids (10.7%), fats and fatty acids (9.58%), ash and minerals (6.58%), and non-flavonoid polyphenols (5.96%). Crude extracts, enriched with bioactive compounds, and isolated compounds from the Grewia species show antioxidant, anticancer, anti-inflammatory, antidiabetic, hepatoprotective/radioprotective, immunomodulatory, and sedative hypnotic potential. Moreover, antimicrobial properties, improvement in learning and memory deficits, and effectiveness against neurodegenerative ailments are also described within the reviewed article. Nowadays, the side effects of some synthetic drugs and therapies, and bottlenecks in the drug development pathway have directed the attention of researchers and pharmaceutical industries towards the development of new products that are safe, cost-effective, and readily available. However, the application of the Grewia species in pharmaceutical industries is still limited.

Occurrence and Health Risk Assessment of Aflatoxins through Intake of Eastern Herbal Medicines Collected from Four Districts of Southern Punjab-Pakistan.

Eastern herbal medicines (HMs) are plant-derived naturally occurring substances with minimum or no industrial processing that have long been used in traditional medicine. Aflatoxins are frequent contaminants of plants. Therefore, these mycotoxins are likely to contaminate HMs and pose a health risk to individuals using them on a regular basis as preventive or curative treatments of various diseases. The present study aimed to determine aflatoxin levels in the most popular Pakistani HM formulations and to assess the health risk associated with the intake of aflatoxins. A total of 400 samples of HM formulations collected from four districts of Punjab were analyzed for the quantification of aflatoxins, out of which 52.5% were found to be contaminated. The average daily dose (ADD) of AFB1 and AFs through the intake of HM formulations ranged between 0.00483 and 0.118 ng/kg bw/day and between 0.00579 and 1.714 ng/kg bw/day, respectively. The margin of exposure (MOE) and population cancer risk ranged from 99.49 to 29378.8 and from 0.00011 to 0.0325 liver cancer cases/105 individuals/year (0.0075-2.455 liver cancer cases/105 individuals/75 years), respectively. Despite the low exposure to aflatoxins from HM formulations in the four studied Punjab (Pakistan) districts, the frequent contamination of the analyzed samples suggests that official measures should be considered to manage the associated risk.

Heterocyclic Aromatic Amines in Meat: Formation, Isolation, Risk Assessment, and Inhibitory Effect of Plant Extracts.

Heterocyclic aromatic amines (HAAs) are potent carcinogenic compounds induced by the Maillard reaction in well-done cooked meats. Free amino acids, protein, creatinine, reducing sugars and nucleosides are major precursors involved in the production of polar and non-polar HAAs. The variety and yield of HAAs are linked with various factors such as meat type, heating time and temperature, cooking method and equipment, fresh meat storage time, raw material and additives, precursor's presence, water activity, and pH level. For the isolation and identification of HAAs, advanced chromatography and spectroscopy techniques have been employed. These potent mutagens are the etiology of several types of human cancers at the ng/g level and are 100- to 2000-fold stronger than that of aflatoxins and benzopyrene, respectively. This review summarizes previous studies on the formation and types of potent mutagenic and/or carcinogenic HAAs in cooked meats. Furthermore, occurrence, risk assessment, and factors affecting HAA formation are discussed in detail. Additionally, sample extraction procedure and quantification techniques to determine these compounds are analyzed and described. Finally, an overview is presented on the promising strategy to mitigate the risk of HAAs by natural compounds and the effect of plant extracts containing antioxidants to reduce or inhibit the formation of these carcinogenic substances in cooked meats.

Human Papillomavirus (HPV): unawareness of the causal role of HPV infection in cervical cancer, HPV vaccine availability, and HPV vaccine uptake among female schoolteachers in a Middle Eastern country.

BACKGROUND: Human papillomavirus (HPV) is the most common viral infection of the reproductive tract. This cross-sectional study among female schoolteachers assessed the prevalence of i) unawareness of HPV infection's causal role in cervical cancer; ii) unawareness of HPV vaccine availability and iii) examined the sociodemographic variables associated both the outcome variables. METHODS: This cross-sectional study was conducted among female schoolteachers employed in public and private sectors schools in Kuwait using a structured questionnaire for data collection. Prevalence of each of the outcome variables was computed. Multivariable logistic regression analyses were used to evaluate independent predictors of two dependent variables. RESULTS: A total 1341 female schoolteachers were enrolled. Of the participants, 60% were unaware of HPV causal role in cervical cancer and 88% were unaware of HPV vaccine availability. Among those who were aware of HPV vaccine availability, 83.8% were unvaccinated. Multivariable logistic regression (MLR) model showed that 20-29 years old participants or those with low family income (< 500 KD/month) were significantly (p < 0.05) more likely to be unaware of HPV causal role in cervical cancer. Moreover, participants with family/ personal history of cervical cancer were significantly (p < 0.05) less likely to be unaware of HPV role in causation of cervical cancer. A separate MLR model revealed that the participants were significantly more likely to be unaware of HPV vaccine availability if they were Kuwaiti nationals or non-Kuwaiti Arabs (p < 0.05), employed in public schools (p = 0.003) or less likely to be unaware if they had personal or family history of cervical cancer (p < 0.001). CONCLUSION: High prevalences of unawareness of causal role of HPV in cervical cancer and unawareness of HPV vaccine availability were recorded. Targeted education among identified sociodemographic groups with high levels of unawareness is warranted. If undertaken, future studies may evaluate the impact of recommended efforts.

Effect of herbal formulation intake on health indices in albino Wistar rat model.

Dyslipidemia management activity of ginger-, garlic-, and lemon-based herbal mixture was tested as paste and herbal extract in hypercholesterolemic adult male albino rats. Atherogenic diet-induced hypercholesterolemia in rats was treated by supplementing the diet with 2.5% herbal paste (4.2 g/kg b.w.) or 2.5 ml oral gavage (20 ml/kg b.w.) of liquid herbal extract daily for 42 days. Hematological and serological outcomes of herbal formulation feeding were compared with the cholesterol-fed positive control and normal control. The results suggest the significant (p < .05) inhibitory properties of herbal paste and liquid extracts against dyslipidemia showing 31%-37%, 62%-68%, and 40%-56% lower levels of total cholesterol, triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), respectively. Treating cholesterol-fed animals with herbal paste and extract significantly (p < .05) increased total protein (5-5.5 g/dl) and serum albumin (3.7-4.2 g/dl) concentration as compared to the normal control. Contrary to significant hypocholesterolemic activity, higher serum total bilirubin levels, that is, 0.70 mg/dl, were observed in rats subchronically exposed to herbal paste and liquid extracts. Nonsignificant (p > .05) impact of herbal formula feeding was observed on hematological indices except lymphocyte counts, that is, 93% in rats fed on herbal paste. The results validate conventional hypocholesterolemic claims associated with ginger-, garlic-, and lemon-based herbal formulations; however, deeper insight into their dose-dependent response in hypercholesterolemia is necessitated to rule out the toxicological impact on the consumer.

Syzygium cumini(L.),Skeels fruit extracts: In vitro and in vivo anti-inflammatory properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium cumini (L.) Skeels is an important medicinal plant utilized in the health care systems of Pakistan, India, Sri Lanka, and Bangladesh. S. cumini have been used to treat renal issues, indigestion, diabetes, dysentery, and employed in folk medicine to treat inflammations. It is known to anticipate antioxidant, anti-inflammatory, anticancer, anti-diabetic, anti-bacterial, antifungal, activities, and radioprotective activities. MATERIAL AND METHODS: We examined the in vitro anti-inflammatory activities of S. cumini fruit extracts, evaluated using membrane stabilization, egg albumin denaturation, and bovine serum albumin denaturation assays. In vivo anti-inflammatory activity was also assessed, using murine models of carrageenan, formaldehyde, and PGE2 induced paw edema. Fractionation of active extracts was performed using HPLC, followed by LC-ESI-MS/MS analysis to identify the bioactive compounds responsible for anti-inflammatory activity. RESULTS: The crude methanolic extract showed stronger in vitro and in vivo anti-inflammatory activities compared to other extracts. The most potent effects were observed in the formaldehyde induced paw edema assay wherein methanolic extract and standard indomethacin induced 72% and 88% inhibition against paw edema volume in comparison to control (normal saline) respectively. In the bovine serum albumin denaturation assay the methanolic extract induced 82% inhibition against denaturation as compared to control (phosphate buffer) while standard diclofenac sodium induced 98% inhibition. In contrast, 50% v/v MeOH:H2O or 100% dichloromethane extracts displayed moderate to weak effects in the anti-inflammatory models. HPLC fractionation provided 6 active sub-fractions, four (MF2, MF3, MF6, MF7) from the 100% methanolic extract and two (HAF1, HAF3) from the 50% methanolic extract. The MF2, MF7, and HAF1 sub-fractions displayed potent activity in all studied in vitro assays. LC-ESI-MS-MS analysis tentatively identified delphinidin 3-glucoside, peonidin-3,5-diglucoside, gallic acid, liquitrigenin, scopoletin, umbelliferon, and rosmanol from the 100% methanolic fractions. Myricetin, catechin, quinic acid, chlorogenic acid, ellagic acid, gallic acid, and caffeic acid were identified in the 50% methanolic fractions. CONCLUSIONS: These results demonstrate that S. cumini fruit extracts are a rich source of bioactive compounds that are worthy of further investigation as leads for anti-inflammatory drug discovery.