Alocasia odora-mediated synthesis of silver nanoparticles, their cytotoxicity, and virucidal potential.

Silver nanoparticles (AgNPs) have various applications in the biomedical field and are considered excellent microbicidal agents. Moreover, biological synthesis of AgNPs using medicinal plants further improves the medicinal applicability of these plants. In this study, the aqueous extract of Alocasia odora rhizome (RE) and Alocasia odora stem (SE) were used to synthesize stem aqueous extract-AgNPs (SNP) and rhizome aqueous extract-AgNPs (RNP). Furthermore, RNP and SNP were evaluated for their virucidal potential. The synthesis of SNP and RNP was monitored using a UV spectrophotometer by observing their surface plasmon resonance peak. In addition, scanning electron microscopy (SEM) gave further insight into their morphology and particle size, whereas energy-dispersive X-ray spectroscopy (EDX) confirmed the presence of silver ions. Interestingly, Fourier-transform infrared spectroscopy (FTIR) analysis of AgNPs revealed that phytomolecules acted as capping and stabilizing agents for SNP and RNP. The in vitro cytotoxicity of SNP and RNP was further analyzed using MTT assay on the U87-MG human glioblastoma cancer cell line and SNP found to be the most cytotoxic (43.40 µg/ml) among all. Besides that, SNP has also found to show the maximum cytopathic effects (CPE) against dengue virus type 2 (DENV-2) on Huh-7 cell line. As a result of the observations, it can be concluded that they can become a promising antiviral drug candidate and thus merit further testing. KEY POINTS: • AgNPs were successfully synthesized through Alocasia odora aqueous extract. • AgNPs were more cytotoxic on the U87-MG cell line than the extract alone. • AgNPs have shown significant reduction in the dengue viral infection than the extract alone.

Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsO2-Induced Aging in Male Rats.

Arsenic (As) poisoning is widespread due to exposure to pollution. The toxic level of (As) causes oxidative stress-induced aging and tissue damage. Since melatonin (MLT) has anti-oxidant and anti-aging properties, we aimed to evaluate the protective effect of MLT against the toxicity of sodium arsenite (NaAsO2). Healthy male NMRI mice were divided into eight different groups. The control group received a standard regular diet. Other groups were treated with varying diets, including MLT alone, NaAsO2, and NaAsO2 plus MLT. After one month of treatment, biochemical and pathological tests were performed on blood, heart, and lung tissue samples. NaAsO2 increased the levels of TNF-α, 8-hydroxy-2-deoxy guanosine (8OHdG), malondialdehyde (MDA), reactive oxygen species (ROS), and high mobility group box 1 (HMGB1), increased the expression of TNF receptor type 1-associated death domain (TRADD) mRNA and telomerase reverse transcriptase, and decreased the expression of Klotho (KL) mRNA in both plasma and tissues. In contrast, MLT reduced MDA, ROS, HMGB1, lactate, and TNF-α enhanced the mRNA expression of KL, and suppressed the mRNA expression of the TERT and TRADD genes. Thus, MLT confers potent protection against NaAsO2- induced tissue injury and oxidative stress.

The role of levosimendan in phosphine-induced cardiotoxicity: evaluation of electrocardiographic, echocardiographic, and biochemical parameters.

Aluminum phosphide (AlP) causes serious poisoning in which severe cardiac suppression is the significant lethal consequence. According to evidence, levosimendan can exert outstanding cardiac support and protection in different pathological conditions. This study aimed to investigate the mechanisms by which levosimendan may alleviate cardiovascular toxicity due to AlP intoxication in the rat model. The groups included control group (normal saline only), sole levosimendan groups (12, 24, 48 µg/kg), AlP group (10 mg/kg), and AlP + levosimendan groups receiving 12, 24, 48 µg/kg levosimendan intraperitoneally 30 min after AlP administration. Electrocardiographic (ECG) parameters (QRS and PR duration and ST height), heart rate, and blood pressure were monitored for 180 minutes. Also, after 24 h of poisoning, echocardiography was applied to assess left ventricle function. Evaluation of the biochemical parameters in heart tissue, including mitochondrial complexes I, II, IV activity, ADP/ATP ratio, the rate of apoptosis, malondialdehyde (MDA), lactate, and troponin I levels, were done after 12 and 24 h. AlP-induced ECG abnormalities (PR duration and ST height), reduction in heart rate, blood pressure, cardiac output, ejection fraction, and stroke volume were improved by levosimendan administration. Besides, levosimendan significantly improved complex IV activity, the ADP/ATP ratio, apoptosis, MDA, lactate, and troponin I level following AlP-poisoning. Our results suggest that levosimendan might alleviate AlP-induced cardiotoxicity by modulating mitochondrial activity and improving cardiac function. However, the potential clinical use of levosimendan in this toxicity needs more investigations.

Therapeutic Effects of Gallic Acid in Regulating Senescence and Diabetes; an In Vitro Study.

Gallic acid (GA), a plant-derived ubiquitous secondary polyphenol metabolite, can be a useful dietary supplement. This in vitro study's primary purpose was to assess the anti-aging properties of GA using rat embryonic fibroblast (REF) cells, antidiabetic effects via pancreatic islet cells, and finally, elucidating the molecular mechanisms of this natural compound. REF and islet cells were isolated from fetuses and pancreas of rats, respectively. Then, several senescence-associated molecular and biochemical parameters, along with antidiabetic markers, were investigated. GA caused a significant decrease in the ß-galactosidase activity and reduced inflammatory cytokines and oxidative stress markers in REF cells. GA reduced the G0/G1 phase in senescent REF cells that led cells to G2/M. Besides, GA improved the function of the ß cells. Flow cytometry and spectrophotometric analysis showed that it reduces apoptosis via inhibiting caspase-9 activity. Taken together, based on the present findings, this polyphenol metabolite at low doses regulates different pathways of senescence and diabetes through its antioxidative stress potential and modulation of mitochondrial complexes activities.

Epigenetic modifications associated with pathophysiological effects of lead exposure.

Lead (Pb) exposure during different stages of development has demonstrated dose, duration, sex, and tissue-specific pathophysiological outcomes due to altered epigenetic regulation via (a) DNA methylation, (b) histone modifications, (c) miRNAs, and (d) chromatin accessibility. Pb-induced alteration of epigenetic regulation causes neurotoxic and extra-neurotoxic pathophysiological outcomes. Neurotoxic effects of Pb include dysfunction of memory and learning, behavioral disorder, attention deficit hyperactivity disorder, autism spectrum disorder, aging, Alzheimer's disease, tauopathy, and neurodegeneration. Extra-neurotoxic effects of Pb include altered body weight, metabolic disorder, cardiovascular disorders, hematopoietic disorder, and reproductive impairment. Pb exposure either early in life or at any stage of development results in undesirable pathophysiological outcomes that tends to sustain and maintain for a lifetime.

Role of purinergic receptors in hepatobiliary carcinoma in Pakistani population: an approach towards proinflammatory role of P2X4 and P2X7 receptors.

The primary malignancy of liver, known as hepatocellular carcinoma (HCC), comprises 9% of all hepatobiliary carcinomas. A steady rise has also been observed in adenocarcinoma (ADC) of the liver and ampullary carcinoma (AMC), ascending to 0.5% of gastrointestinal malignancies. Hepatobiliary carcinomas consist of 13% of all cancer occurrences worldwide. Purinergic receptor-based signaling holds the therapeutic potential based on its role in cell proliferation of several carcinomas. An altered ATP concentration in nanomoles may lead towards crucial changes in cancer growth patterns in liver tissue. A total of 40 tissue samples were collected (20 samples of HCC, 10 samples of ADC, and 10 samples of AMC) from patients that underwent surgery. P2X4 and P2X7 receptors exhibited significantly increased expression in HCC, ADC, and AMC samples as compared with the control tissue samples. While ADC and AMC samples showed higher expression of P2X4 and P2X7 than the control, statistically, HCC samples exhibited the most significant expression of both P2X4 and P2X7 receptors than control tissues. It may be inferred that higher expression of P2X4 and P2X7 receptors is significantly associated with the upregulated cellular stress leading to inflammation and it is plausible that both these receptors may be used in diagnostic, prognostic, and therapeutic tools for carcinoma studies in the future.

Purinoceptor expression in hepatocellular virus (HCV)-induced and non-HCV hepatocellular carcinoma: an insight into the proviral role of the P2X4 receptor.

The basic idea behind this study was to discover the association and prevalence of purinoceptors in hepatitis C virus (HCV) and non-HCV hepatocellular carcinoma (HCC). Immunohistochemistry was performed to study the expression of P2X4 and P2X7 receptors on ex-planted liver tissue samples that were collected from HCC patients. Antibodies specific for the P2X4 and P2X7 receptors were used to target the specific receptors and secondary antibody was used with 3,3'-diaminobenzidine (DAB) detection system to visualize the color change in case of any positive expression There was a substantial increase in P2X4 receptor expression in HCV induced HCC as compared to non-HCV HCC. Surprisingly, there was no increase in the P2X7 receptor expression in both HCV HCC and non-HCV HCC. We conclude that P2X4 receptor expression was significant in the presence of HCV HCC. This may confirms the potential role of P2X4 receptor in the presence of virus in liver pathology. However insignificant expression of P2X7 receptor may avert our attention towards understanding the role of this receptor in pro-inflammatory and immune responses.

Evaluation of DNA vaccines encoding M. Tb gene Bfrb and Mpt32 in mice model.

Tuberculosis (TB) is a life threatening infectious disease which is prevalent throughout the world. Mycobacterium bovis based Bacille Calmette-Gue´rin (BCG) is the only vaccine available against TB however, this (single) vaccine is not enough to eradicate it. Furthermore, numbers of researches from different parts of the World have shown its efficacy as variable. Hence other (better) vaccines like DNA vaccines are needed in addition to BCG in order to achieve desired goal of TB eradication. The current study was aimed to develop subunit based DNA vaccines against TB and to check their efficacy. Two constructs Bfrb-pND14 and Mpt32-pND14 were made and used as DNA vaccines. Endotoxin free DNA preparations were made and used in immunization studies. Twenty Balb/c female mice of age eight weeks were used in trial. Two experimental groups each comprising eight animals were used to inoculate Mpt32-pND14 and Bfrb-pND14 vaccines respectively. A group of four animals was used as negative control. Animals were bled through tail periodically and finally through cardiac puncture before euthanization. Antibodies were confirmed through dot blot and Agar Gel Immuno Diffusion test (AGID). All the animals immunized with both vaccines were found positive as tested through dot blot and AGID. The results of this study have indicated that both the M. tb genes have produced strong immune response in mice model through pND14 vector and proved themselves as good subunit based DNA vaccines.

Current and future therapies for hepatitis C virus infection: from viral proteins to host targets.

Hepatitis C virus (HCV) infection is the most important problem across the world. It causes acute and chronic liver infection. Different approaches are in use to inhibit HCV infection, including small organic compounds, siRNA, shRNA and peptide inhibitors. This review article summarizes the current and future therapies for HCV infection. PubMed and Google Scholar were searched for articles published in English to give an insight into the current inhibitors against this life-threatening virus. HCV NS3/4A protease inhibitors and nucleoside/nucleotide inhibitors of NS5B polymerase are presently in the most progressive stage of clinical development, but they are linked with the development of resistance and viral breakthrough. Boceprevir and telaprevir are the two most important protease inhibitors that have been approved recently for the treatment of HCV infection. These two drugs are now the part of standard-of-care treatment (SOC). There are also many other drugs in phase III of clinical development. When exploring the various host-cell-targeting compounds, the most hopeful results have been demonstrated by cyclophilin inhibitors. The current SOC treatment of HCV infection is Peg-interferon, ribavirin and protease inhibitors (boceprevir or telaprevir). The future treatment of this life-threatening disease must involve combinations of therapies hitting multiple targets of HCV and host factors. It is strongly expected that the near future, treatment of HCV infection will be a combination of direct-acting agents (DAA) without the involvement of interferon to eliminate its side effects.

Role of viral and host factors in interferon based therapy of hepatitis C virus infection.

The current standard of care (SOC) for hepatitis C virus (HCV) infection is the combination of pegylated interferon (PEG-IFN), Ribavirin and protease inhibitor for HCV genotype 1. Nevertheless, this treatment is successful only in 70-80% of the patients. In addition, the treatment is not economical and is of immense physical burden for the subject. It has been established now, that virus-host interactions play a significant role in determining treatment outcomes. Therefore identifying biological markers that may predict the treatment response and hence treatment outcome would be useful. Both IFN and Ribavirin mainly act by modulating the immune system of the patient. Therefore, the treatment response is influenced by genetic variations of the human as well as the HCV genome. The goal of this review article is to summarize the impact of recent scientific advances in this area regarding the understanding of human and HCV genetic variations and their effect on treatment outcomes. Google scholar and PubMed have been used for literature research. Among the host factors, the most prominent associations are polymorphisms within the region of the interleukin 28B (IL28B) gene, but variations in other cytokine genes have also been linked with the treatment outcome. Among the viral factors, HCV genotypes are noteworthy. Moreover, for sustained virological responses (SVR), variations in core, p7, non-structural 2 (NS2), NS3 and NS5A genes are also important. However, all considered single nucleotide polymorphisms (SNPs) of IL28B and viral genotypes are the most important predictors for interferon based therapy of HCV infection.

Clinical and biochemical determinants of length of stay, readmission and recurrence in patients admitted with diabetic ketoacidosis.

BACKGROUND: The increasing prevalence of diabetic ketoacidosis (DKA) related admissions poses a significant burden on the healthcare systems globally. However, data regarding the predictors of healthcare resource utilization in DKA is limited and inconsistent. This study aimed to identify key predictors of hospital length of stay (LOS), readmission and recurrent DKA episodes. METHODS: We undertook a retrospective cross-sectional analysis of all DKA admissions from 2015 to 2021 across four hospitals in Qatar. The primary outcomes were the length of stay (LOS), 90-day readmission and 6-month and 1-year DKA recurrence. RESULTS: We included 922 patients with a median age of 35 years (25-45). 62% were males with type-1 diabetes-mellitus (T1DM) and type-2 DM (T2DM), present in 52% and 48% of patients. The median LOS was 2.6 days (IQR 1.1-4.8), and the median DKA resolution time was 18 h (10.5-29). Male-gender, new-onset DM, higher Charlson Comorbidity Index (CCI), lower haemoglobin, sodium and potassium, higher urea, longer DKA duration and MICU admission predicted a longer LOS in a multivariate regression analysis. None of the factors were significantly associated with 90-day readmission. Patients with pre-existing T1DM were more likely to have a six-month DKA recurrence than pre-existing T2DM. Patients with a 6-month DKA recurrence, female gender and T1DM had higher odds of 12-month recurrence, whereas a consult with a diabetes educator at the index admission was associated with decreased odds of recurrence. CONCLUSIONS/INTERPRETATION: This is the most extensive study from the Middle-East region reporting on LOS, readmissions and the recurrence of DKA. Results from this study with a diverse population may be valuable for physicians and healthcare systems to decrease the diabetes-related healthcare burden in DKA patients.

P2X4 receptors mediate induction of antioxidants, fibrogenic cytokines and ECM transcripts; in presence of replicating HCV in in vitro setting: An insight into role of P2X4 in fibrosis.

BACKGROUND & AIMS: Major HCV infections lead to chronic hepatitis, which results in progressive liver disease including fibrosis, cirrhosis and eventually hepatocellular carcinoma (HCC). P2X4 and P2X7 are most widely distributed receptors on hepatocytes. METHODS: Full length P2X4 (1.7kb) (Rattus norvegicus) was sub cloned in mammalian expression vector pcDNA3.1+. Two stable cell lines 293T/P2X4 (experimental) and 293T/ NV or null vector (control) were established. Both cell lines were inoculated with high viral titers human HCV sera and control human sera. Successfully infected cells harvested on day 5 and day 9 of post infection were used for further studies. RESULTS: The results revealed a significant increase in gene expression of P2X4 on day 5 and day 9 Post -infection in cells infected with HCV sera compared with cells inoculated with control sera. Quantitative real time PCR analysis revealed that HO-1 was significantly upregulated in presence of P2X4 in HCV infected cells (P2X4/HCV) when compared with control NV/HCV cells. A significant decrease was observed in expression of Cu/ZnSOD in presence of P2X4 in HCV infected cells compared to control NV/HCV cells. However, expression of both antioxidants was observed unaltered in cells harvested on day 9 post infection. Gene expression of angiotensin II significantly increased in HCV infected cells in presence of P2X4 on day 5 and day 9 of post infection when compared with control NV/HCV cells. A significant increase in gene expression of TNF-α and TGF-ß was observed in HCV infected cells in presence of P2X4 on day 9 post infection in comparison with control (NV/HCV cells). However, gene expression of adipokine leptin was not affected in both experimental (P2X4/HCV) and control (NV/HCV) groups on day 5 and day 9 of post infection. Extracellular matrix proteins, laminin and elastin genes expression also significantly increased in presence of P2X4 (HCV/P2X4) on day 9 of post-infection compared to control group NV/HCV cells. CONCLUSION: In conclusion, these findings constitute the evidence that P2X4 receptors in the presence of HCV play a significant role in the regulation of key antioxidant enzymes (HO-1, Cu/ZnSOD), in the induction of proinflammatory. cytokine (TNF-α), profibrotic cytokine (TGF-ß) vasoactive cytokine (angiotensin II). P2X4 also increases the expression of extracellular matrix proteins (laminin and elastin) in the presence of HCV.

Clinically significant findings of high-risk mutations in human SLC29A4 gene associated with diabetes mellitus type 2 in Pakistani population.

This study conducted an in-depth analysis combining computational and experimental verifications of the deleterious missense mutations associated with the SLC29A4 protein. The functional annotation of the non-synonymous single nucleotide polymorphism (nsSNPs), followed by structure-function analysis, revealed 13 single nucleotide polymorphisms (SNP) as the most damaging. Among these, six mutants P429T/S, L144S, M108V, N86H, and V79E, were predicted as structurally and functionally damaging by protein stability analysis. Also, these variants are located at evolutionary conserved regions, either buried, contributing to the structural damage, or exposed, causing functional changes in the protein. These mutants were further taken for molecular docking studies. When verified via experimental analysis, the SNPs M108V (rs149798710), N86H (rs151039853), and V79E (rs17854505) showed an association with type 2 diabetes mellitus (T2DM). Minor allele frequency for rs149798710 (A > G) was 0.23 in controls, 0.29 in metformin responders, 0.37 in metformin non-responder, for rs151039853 (A > C) was 0.21 in controls, 0.28 in metformin responders, 0.36 in metformin non-responder and for rs17854505 (T > A) was 0.20 in controls, 0.25 in metformin responders, 0.37 in metformin non-responder. Hence, this study concludes that SLC29A4 M108V (rs149798710), N86H (rs151039853), and V79E (rs17854505) polymorphisms were associated with the increased risk of T2DM as well as with the increased risk towards the failure of metformin therapeutic response in T2DM patients of Pakistan. Communicated by Ramaswamy H. Sarma.

Lead inhibits the odontogenic differentiation potential of dental pulp stem cells by affecting WNT1/ß-catenin signaling and related miRNAs expression.

Lead (Pb) is ubiquitous in environment that accumulates in teeth and calcified tissues from where it releases gradually with aging and adversely affects dental health. This study aimed to determine the effect of Pb exposure on odontogenic differentiation potential of isolated human dental pulp stem cells and investigate the possible underlying epigenetic factors. In the absence of Pb exposure, stem cells displayed significant odontogenic markers including elevated Alkaline Phosphatase (ALP) activity, Alizarin red staining intensity, and increased expression of odontogenic DMP1 and DSPP genes. Exposure to 60 µM Pb resulted in reduced ALP activity and calcium deposition. Also, diminished expression of RUNX2, DMP1, and DSPP, as well as Wnt signaling mediators including WNT1, and ß-catenin were detected. The expression of Wnt signaling related microRNAs, miRNA-139-5p and miRNA-142-3p, on the other hand, were shown to have a significant increase. We concluded that Pb could adversely affect the odontogenic differentiation potential of dental pulp stem cell. The underlying mechanism might related to Pb-induced epigenetic dysregulation of WNT1/ß-catenin pathway-related miRNAs leading to down-regulation of Wnt/ß-catenin related odontogenic genes and eventually impaired odontogenic differentiation process.

The Effect of Levosimendan on Phosphine-Induced Nephrotoxicity: Biochemical and Histopathological Assessment.

BACKGROUND: Aluminum phosphide (AlP) toxicity is associated with a high risk of death due to heart, liver, and kidney failure as the target organs. Phosphine gas released due to the ingestion is the main factor involved in the multi-organ failure with various mechanisms. Levosimendan (LEV) is a calcium sensitizer with a pleiotropic effect on multiple organs. This study aimed to investigate whether LEV can alleviate AlP-induced nephrotoxicity in the rat model. METHOD: Six groups included control group (almond oil only), sole LEV group (48 µg/kg), AlP group (LD50=10 µg/kg), and the poisoned groups treated with LEV at doses of 12, 24, and 48 µg/kg 30 min after AlP gavage. After 24 hours of treatment, serum and kidney samples were taken for biochemical and histopathological analyses. RESULT: Biochemical analysis of the AlP group showed that the activity of complexes I, II, and IV was significantly reduced, while the levels of lipid peroxidation (LPO) and reactive oxygen species (ROS), lactate, and myeloperoxidase (MPO) activity significantly increased. Also, AlP reduced live renal cells and elevated necrosis. However, the levels of serum creatinine and blood urea nitrogen were not affected by the poisoning. LEV co-treatment could increase mitochondrial complex activity and reduce MPO activity, LPO, ROS, and lactate levels. Additionally, the histopathological analysis showed the detrimental effects of AlP on kidney tissue, which was mitigated by LEV administration. CONCLUSION: Our findings showed that LEV can potentially improve oxidative stress, imbalance in the redox status, necrosis, and pathological injuries in kidney tissue following AlP-poisoning.

Risk variants of obesity associated genes demonstrate BMI raising effect in a large cohort.

Obesity is highly polygenic disease where several genetic variants have been reportedly associated with obesity in different ethnicities of the world. In the current study, we identified the obesity risk or protective association and BMI raising effect of the minor allele of adiponectin, C1Q and collagen domain containing (ADIPOQ), cholesteryl ester transfer protein (CEPT), FTO alpha-ketoglutarate dependent dioxygenase (FTO), leptin (LEP), and leptin receptor (LEPR) genes in a large cohort stratified into four BMI-based body weight categories i.e., normal weight, lean, over-weight, and obese. Based on selected candidate genetic markers, the genotyping of all study subjects was performed by PCR assays, and genotypes and allele frequencies were calculated. The minor allele frequencies (MAFs) of all genetic markers were computed for total and BMI-based body weight categories and compared with MAFs of global and South Asian (SAS) populations. Genetic associations of variants with obesity risk were calculated and BMI raising effect per copy of the minor allele were estimated. The genetic variants with higher MAFs in obese BMI group were; rs2241766 (G = 0.43), rs17817449 (G = 0.54), rs9939609 (A = 0.51), rs1421085 (C = 0.53), rs1558902 (A = 0.63), and rs1137101 (G = 0.64) respectively. All these variants were significantly associated with obesity (OR = 1.03-4.42) and showed a high BMI raising effect (ß = 0.239-0.31 Kg/m2) per copy of the risk allele. In contrast, the MAFs of three variants were higher in lean-normal BMI groups; rs3764261 A = 0.38, rs9941349 T = 0.43, and rs7799039 G = 0.40-0.43). These variants showed obesity protective associations (OR = 0.68-0.76), and a BMI lowering effect per copy of the protective allele (ß = -0.103-0.155 Kg/m2). The rs3764261 variant also showed significant and positive association with lean body mass (OR = 2.38, CI = 1.30-4.34). Overall, we report six genetic variants of ADIPOQ, FTO and LEPR genes as obesity-risk markers and a CETP gene variant as lean mass/obesity protective marker in studied Pakistani cohort.

Environmental Distribution of Personal Care Products and Their Effects on Human Health.

Personal care products (PCPs) are generally used for personal hygiene, cleaning, grooming, and beautification. These include hair and skin care products, baby care products, UV blocking creams, facial cleansers, insect repellents, perfumes, fragrances, soap, detergents, shampoos, conditioners, toothpaste, etc., thus exposing humans easily. Personal preferences related to PCPs usage frequency are highly variable and depend on socioeconomic status and lifestyle factors. The increasing availability and diversity of PCPs from the retailer outlets consequently result in higher loading of PCPs into wastewater systems and, therefore, the environment. These compounds persistently and continuously release biologically active and inactive ingredients in the atmosphere, biosphere, geosphere, and demonstrating adverse effects on human, wild, and marine life. Advanced techniques such as granular activated carbon filtration and algae-based system may help biotransformation and remove PCP contaminants from water with improved efficiency. Additionally, harmony among PCPs related regulations of different countries may encourage standard checks to control their manufacturing, sale, and distribution across the borders to ensure consumers' safety. Furthermore, all intended ingredients, their concentrations, and instructions for frequency of use as per age groups may be clearly labeled on packages of PCPs. In conclusion, the emerging environmental contaminants of PCPs and their association with the growing risks of negative effects on human health and globally on the environment emphasize the chemical-free simple lifestyle.

Fungal infections following liver transplantation.

With increasing morbidity and mortality from chronic liver disease and acute liver failure, the need for liver transplantation is on the rise. Most of these patients are extremely vulnerable to infections as they are immune-compromised and have other chronic co-morbid conditions. Despite the recent advances in practice and improvement in diagnostic surveillance and treatment modalities, a major portion of these patients continue to be affected by post-transplant infections. Of these, fungal infections are particularly notorious given their vague and insidious onset and are very challenging to diagnose. This mini-review aims to discuss the incidence of fungal infections following liver transplantation, the different fungi involved, the risk factors, which predispose these patients to such infections, associated diagnostic challenges, and the role of prophylaxis. The population at risk is increasingly old and frail, suffering from various other co-morbid conditions, and needs special attention. To improve care and to decrease the burden of such infections, we need to identify the at-risk population with more robust clinical and diagnostic parameters. A more robust global consensus and stringent guidelines are needed to fight against resistant microbes and maintain the longevity of current antimicrobial therapies.

Environmental Exposure to Heavy Metals Contributes to Diseases Via Deregulated Wnt Signaling Pathways.

Wnt signaling plays a critical role during embryogenesis and is responsible for regulating the homeostasis of the adult stem cells and cells fate via a multitude of signaling pathways and associated transcription factors, receptors, effectors, and inhibitors. For this review, published articles were searched from PubMed Central, Embase, Medline, and Google Scholar. The search terms were Wnt, canonical, noncanonical, signaling pathway, ß - catenin, environment, and heavy metals. Published articles on Wnt signaling pathways and heavy metals as contributing factors for causing diseases via influencing Wnt signaling pathways were included. Wnt canonical or noncanonical signaling pathways are the key regulators of stem cell homeostasis that control many mechanisms. There is an adequate balance between ß - catenin dependent and independent Wnt signaling pathways and remain highly conserved throughout different development stages. Environmental heavy metal exposure may cause either inhibition or overexpression of any component of Wnt signaling pathways such as Wnt protein, transcription factors, receptors, ligands, or transducers to impede normal cellular function via negatively affecting Wnt signaling pathways. Environmental exposure to heavy metals potentially contributes to diseases via deregulated Wnt signaling pathways.

Associations Between Food Insecurity and Common Mental Health Problems Among Reproductive-Aged Women in Kabul-Afghanistan.

Background: Food insecurity has been linked to poor health outcomes, however this relationship is poorly understood among women of reproductive age. Therefore, we investigated the relationship between food insecurity and common mental health problems (CMHPs) in this population of women in Kabul, Afghanistan. Method: A cross-sectional study was conducted with 421 women of reproductive age from four health centers located in four randomly selected zones in the city of Kabul. We used the United State Department of Agriculture (USDA) food-insecurity questionnaire, multiple 24-h recall for dietary intake, the Depression, the Anxiety and Stress Scale (DASS-21) to assess major mental health problems, and the International Physical Activity Questionnaire (IPAQ) to assess physical activity. Result: Food insecurity affected 69.6% of reproductive-aged women. In total, 44.9, 10.9, and 13.9% of food-insecure participants had food insecurity without hunger, food insecurity with hunger, and food insecurity with severe hunger, respectively. Depression, anxiety, and stress were prevalent among food-insecure participants at 89.4, 90.8, and 85.7%, respectively. Food insecurity was associated with depression (OR = 4.9, 95% CI: 2.7-8.9), anxiety (OR = 4.7, 95% CI: 2.5-8.8), and stress (OR = 3.8, 95% CI: 2.2-6.7). Women's household ownership, family size, and hypertension, on the other hand, were not associated with food insecurity. Conclusion: This study found food insecurity was associated with CMHPs among a sample of reproductive-aged women in Kabul, Afghanistan. Further longitudinal studies are needed to confirm these findings.