Search Results (164)

Cytochrome P450s (CYPs) are the most prominent family of enzymes involved in NADPH- and O₂-dependent hydroxylation processes throughout all spheres of life. CYPs are crucial for the detoxification of xenobiotics in plants, insects, and other organisms. In addition to performing this function, CYPs serve as flexible catalysts and are essential for producing secondary metabolites, antioxidants, and phytohormones in higher plants. Numerous biotic and abiotic stresses frequently affect the growth and development of plants. They cause a dramatic decrease in crop yield and a deterioration in crop quality. Plants protect themselves against these stresses through different mechanisms, which are accomplished by the active participation of CYPs in several biosynthetic and detoxifying pathways. There are immense potentialities for using CYPs as a candidate for developing agricultural crop species resistant to biotic and abiotic stressors. This review provides an overview of the plant CYP families and their functions to plant secondary metabolite production and defense against different biotic and abiotic stresses. Full article

The psychedelic renaissance has reignited interest in the therapeutic potential of psychedelics for mental health and well-being. An emerging area of interest is the potential modulation of psychedelic effects by the gut microbiome—the ecosystem of microorganisms in our digestive tract. This review explores the intersection of the gut microbiome and psychedelic therapy, underlining potential implications for personalized medicine and mental health. We delve into the current understanding of the gut–brain axis, its influence on mood, cognition, and behavior, and how the microbiome may affect the metabolism and bioavailability of psychedelic substances. We also discuss the role of microbiome variations in shaping individual responses to psychedelics, along with potential risks and benefits. Moreover, we consider the prospect of microbiome-targeted interventions as a fresh approach to boost or modulate psychedelic therapy’s effectiveness. By integrating insights from the fields of psychopharmacology, microbiology, and neuroscience, our objective is to advance knowledge about the intricate relationship between the microbiome and psychedelic substances, thereby paving the way for novel strategies to optimize mental health outcomes amid the ongoing psychedelic renaissance. Full article

Recent European data facilitate an epidemiological investigation of the controversial cannabis–cancer relationship. Of particular concern were prior findings associating high-dose cannabis use with reproductive problems and potential genetic impacts. Cancer incidence data age-standardised to the world population was obtained from the European Cancer Information System 2000–2020 and many European national cancer registries. Drug use data were obtained from the European Monitoring Centre for Drugs and Drug Addiction. Alcohol and tobacco consumption was sourced from the WHO. Median household income was taken from the World bank. Cancer rates in high-cannabis-use countries were significantly higher than elsewhere (β-estimate = 0.4165, p = 3.54 × 10⁻¹¹⁵). Eighteen of forty-one cancers (42,675 individual rates) were significantly associated with cannabis exposure at bivariate analysis. Twenty-five cancers were linked in inverse-probability-weighted multivariate models. Temporal lagging in panel models intensified these effects. In multivariable models, cannabis was a more powerful correlate of cancer incidence than tobacco or alcohol. Reproductive toxicity was evidenced by the involvement of testis, ovary, prostate and breast cancers and because some of the myeloid and lymphoid leukaemias implicated occur in childhood, indicating inherited intergenerational genotoxicity. Cannabis is a more important carcinogen than tobacco and alcohol and fulfills epidemiological qualitative and quantitative criteria for causality for 25/41 cancers. Reproductive and transgenerational effects are prominent. These findings confirm the clinical and epidemiological salience of cannabis as a major multigenerational community carcinogen. Full article

Vulvovaginitis with Candida spp. is the most common infection in women and the rate is increased during pregnancy. Antifungal prescription in pregnant women continues to present challenges and the decision must balance the risk of fetal toxicity with the benefits to the fetus and mother. Starting from the idea that clotrimazole is the most recommended antifungal in candidal vaginitis in pregnancy, we tested the sensitivity of different species of Candida spp. to other azoles, polyenes, and antimetabolites. This retrospective study (January to June 2019) assessed 663 pregnant women hospitalized for various pregnancy-related symptoms in which samples of phage secretion were taken. The laboratory results confirmed 21% of cases, indicating 140 positive mycologic samples. In this study, vaginal candidiasis was mostly related to the first trimester of pregnancy (53.57%,) and less related in the last trimester (17.14%). Candida albicans was the most frequent isolated strain in this study, accounting for 118 cases, followed by 16 strains of Candida glabrata and 6 cases of Candida krusei. The highest sensitivity for C. albicans was found in azoles, mostly in miconazole (93.2%), while C. krusei was completely resistant to polyene with low sensitivity in antimetabolites and even in some azoles, such as fluconazole. In our study, higher resistance rates to flucytosine were found, with C. glabrata and C. krusei exhibiting greater resistance than C. albicans. Full article

Consumption of maize and maize-based products contributes a significant percentage to the total food energy intake in Uganda. However, the production of maize-derived foodstuffs is performed traditionally or by small- and medium-scale processors using different processing techniques. This can lead to differences in the quality of these products from processors, raising food safety concerns. In this study, the effects of mechanical processing (milling) methods on deposition of heavy metals into milled maize flour and the associated consumption health risks were assessed. Atomic absorption spectrophotometry was used to quantitatively establish the concentration of iron (Fe), manganese (Mn), zinc (Zn), cadmium (Cd), lead (Pb), chromium (Cr), copper (Cu), cobalt (Co) and nickel (Ni) in 100 samples of maize milled using a wooden mortar (n = 2), a metallic mortar (n = 2), diesel engine−powered mills (n = 48) and electric motor−powered mills (n = 48). Results showed that the mean concentrations of heavy metals in mg/kg were Fe (11.60–34.45), Cu (0.50–8.10), Ni (0.50–1.60), Mn (0.70–25.40), Zn (4.40–15.90), Pb (0.53–10.20), Cd (0.51–0.85), Cr (0.50–1.53) and Co (0.50–1.51). The highest concentrations were found in flour milled using a traditional metallic mortar while the lowest levels were in those samples milled using a wooden mortar. The Fe, Pb and Cd contents of flours produced using the metallic mortar and some commercial mills was found to be higher than the permissible limits set by WHO/FAO. Human health risk assessment showed that there are potential carcinogenic health risks from adults’ intake of heavy metals in maize flour milled using a metallic mortar. Therefore, processing of maize flour needs to be monitored by the relevant statutory bodies in Uganda to minimize the possibility of heavy metal contamination of food products and animal feeds. Full article

Embryogenesis is a well-coordinated process relying on precise cues and environmental signals that direct spatiotemporal embryonic patterning. Quite often, when one error in this process occurs, others tend to co-occur. We posit that investigating the co-occurrence of these abnormalities over time would yield additional information about the mode of toxicity for chemicals. Here, we use the environmental contaminant tris(4-chlorophenyl)methanol (TCPMOH) as a model toxicant to assess the relationship between exposures and co-occurrence of developmental abnormalities in zebrafish embryos. We propose a dynamic network modeling approach to study the co-occurrence of abnormalities, including pericardial edema, yolk sac edema, cranial malformation, spinal deformity, delayed/failed swim bladder inflation, and mortality induced by TCPMOH exposure. TCPMOH-exposed samples revealed increased abnormality co-occurrence when compared to controls. The abnormalities were represented as nodes in the dynamic network model. Abnormalities with high co-occurrence over time were identified using network centrality scores. We found that the temporal patterns of abnormality co-occurrence varied between exposure groups. In particular, the high TCPMOH exposure group experienced abnormality co-occurrence earlier than the low exposure group. The network model also revealed that pericardial and yolk sac edema are the most common critical nodes among all TCPMOH exposure levels, preceding further abnormalities. Overall, this study introduces a dynamic network model as a tool for assessing developmental toxicology, integrating structural and temporal features with a concentration response. Full article

Chemical fungicides are the backbone of modern agriculture, but an alternative formulation is necessary for sustainable crop production to address human health issues and soil/water environmental pollution. So, a green chemistry approach was used to form guar gum nanoemulsions (NEs) of 186.5–394.1 nm containing the chemical fungicide mancozeb and was characterized using various physio-chemical techniques. An 84.5% inhibition was shown by 1.5 mg/mL mancozeb-loaded NEs (GG-1.5) against A. alternata, comparable to commercial mancozeb (86.5 ± 0.7%). The highest mycelial inhibition was exhibited against S. lycopersici and S. sclerotiorum. In tomatoes and potatoes, NEs showed superior antifungal efficacy in pot conditions besides plant growth parameters (germination percentage, root/shoot ratio and dry biomass). About 98% of the commercial mancozeb was released in just two h, while only about 43% of mancozeb was released from nanoemulsions (0.5, 1.0 and 1.5) for the same time. The most significant results for cell viability were seen at 1.0 mg/mL concentration of treatment, where wide gaps in cell viability were observed for commercial mancozeb (21.67%) and NEs treatments (63.83–71.88%). Thus, this study may help to combat the soil and water pollution menace of harmful chemical pesticides besides protecting vegetable crops. Full article

In the age of industrialization, numerous non-biodegradable pollutants like plastics, HMs, polychlorinated biphenyls, and various agrochemicals are a serious concern. These harmful toxic compounds pose a serious threat to food security because they enter the food chain through agricultural land and water. Physical and chemical techniques are used to remove HMs from contaminated soil. Microbial-metal interaction, a novel but underutilized strategy, might be used to lessen the stress caused by metals on plants. For reclaiming areas with high levels of heavy metal contamination, bioremediation is effective and environmentally friendly. In this study, the mechanism of action of endophytic bacteria that promote plant growth and survival in polluted soils—known as heavy metal-tolerant plant growth-promoting (HMT-PGP) microorganisms—and their function in the control of plant metal stress are examined. Numerous bacterial species, such as Arthrobacter, Bacillus, Burkholderia, Pseudomonas, and Stenotrophomonas, as well as a few fungi, such as Mucor, Talaromyces, Trichoderma, and Archaea, such as Natrialba and Haloferax, have also been identified as potent bioresources for biological clean-up. In this study, we additionally emphasize the role of plant growth-promoting bacteria (PGPB) in supporting the economical and environmentally friendly bioremediation of heavy hazardous metals. This study also emphasizes future potential and constraints, integrated metabolomics approaches, and the use of nanoparticles in microbial bioremediation for HMs. Full article

With the legalization of marijuana smoking in several states of the United States and many other countries for medicinal and recreational use, the possibility of its release into the environment cannot be overruled. Currently, the environmental levels of marijuana metabolites are not monitored on a regular basis, and their stability in the environment is not well understood. Laboratory studies have linked delta 9-tetrahydrocannabinol (Δ⁹-THC) exposure with behavioral abnormalities in some fish species; however, their effects on endocrine organs are less understood. To understand the effects of THC on the brain and gonads, we exposed adult medaka (Oryzias latipes, Hd-rR strain, both male and female) to 50 ug/L THC for 21 days spanning their complete spermatogenic and oogenic cycles. We examined transcriptional responses of the brain and gonads (testis and ovary) to Δ⁹-THC, particularly molecular pathways associated with behavioral and reproductive functions. The Δ⁹-THC effects were more profound in males than females. The Δ⁹-THC-induced differential expression pattern of genes in the brain of the male fish suggested pathways to neurodegenerative diseases and pathways to reproductive impairment in the testis. The present results provide insights into endocrine disruption in aquatic organisms due to environmental cannabinoid compounds. Full article

Selective Androgen Receptor Modulators (SARMs) are not FDA approved, and obtaining SARMs for personal use is illegal. Nevertheless, SARM use is increasingly popular amongst recreational athletes. Recent case reports of drug-induced liver injury (DILI) and tendon rupture raise serious concerns for the safety of recreational SARM users. On 10 November 2022 PubMed, Scopus, Web of Science, and ClinicalTrials.gov were searched for studies that reported safety data of SARMs. A multi-tiered screening approach was utilized, and any study or case report of generally healthy individuals exposed to any SARM was included. Thirty-three studies were included in the review with 15 case reports or case series and 18 clinical trials (total patients N = 2136 patients, exposed to SARM N = 1447). There were case reports of drug-induced liver injury (DILI) (N = 15), Achilles tendon rupture (N = 1), rhabdomyolysis (N = 1), and mild reversible liver enzyme elevation (N = 1). Elevated alanine aminotransferase (ALT) was commonly reported in clinical trials in patients exposed to SARM (mean 7.1% across trials). Two individuals exposed to GSK2881078 in a clinical trial were reported to have rhabdomyolysis. Recreational SARM use should be strongly discouraged, and the risks of DILI, rhabdomyolysis, and tendon rupture should be emphasized. However, despite warnings, if a patient refuses to discontinue SARM use, ALT monitoring or dose reduction may improve early detection and prevention of DILI. Full article

Accurate predictions of drug uptake transporter involvement in renal excretion of xenobiotics require determination of in vitro transport kinetic parameters under initial-rate conditions. The purpose of the present study was to determine how changing the incubation time from initial rate to steady state influences ligand interactions with the renal organic anion transporter 1 (OAT1), and the impact of the different experimental conditions on pharmacokinetic predictions. Transport studies were performed with Chinese hamster ovary cells expressing OAT1 (CHO-OAT1) and the Simcyp Simulator was used for physiological-based pharmacokinetic predictions. Maximal transport rate and intrinsic uptake clearance (CL_int) for PAH decreased with increasing incubation time. The CL_int values ranged 11-fold with incubation times spanning from 15 s (CL_int,15s, initial rate) to 45 min (CL_int,45min, steady state). The Michaelis constant (K_m) was also influenced by the incubation time with an apparent increase in the Km value at longer incubation times. Inhibition potency of five drugs against PAH transport was tested using incubation times of either 15 s or 10 min. There was no effect of time on inhibition potency for omeprazole or furosemide, whereas indomethacin was less potent, and probenecid (~2-fold) and telmisartan (~7-fold) more potent with the longer incubation time. Notably, the inhibitory effect of telmisartan was reversible, albeit slowly. A pharmacokinetic model was developed for PAH using the CL_int,15s value. The simulated plasma concentration-time profile, renal clearance, and cumulative urinary excretion-time profile of PAH agreed well with reported clinical data, and the PK parameters were sensitive to the time-associated CL_int value used in the model. Full article

According to recent literature, there is a limited amount of data about the correlation of vitamin 25(OH)D, potassium (K), oxidative stress parameters, and other biomarkers with dyslipidemia, which is an established risk factor for cardiovascular diseases (CVDs). This study aims to investigate the correlation of lipid profile and atheromatic index TC/HDL with several biomarkers and oxidative stress parameters. A total of 102 volunteers, 67 with atheromatic index TC/HDL > 3.5 (Group A) and 35 with TC/HDL < 3.5 (Group B), aged from 26 to 78 years, participated in this study. Serum levels of triglycerides (TG), total cholesterol (TC), low- and high-density lipoproteins (LDL and HDL), vitamin 25(OH)D [25(OH)D], potassium (K), sodium (Na), lactose dehydrogenase (LDH), liver enzymes including serum glutamic oxaloacetic and glutamic pyruvic transaminases (SGOT and SGPT), gamma-glutamyl transferase (γ-GT), and alkaline phosphatase (ALP) were analyzed using standard photometric methods. Oxidative stress parameters such as reactive oxygen species (ROS) were detected with fluorometric methods, whereas total oxidative (TOS) and antioxidative status (TAS) were measured with spectrophotometric methods. According to the results, negative correlations of HDL (r = −0.593) and 25(OH)D (r = −0.340) and K (r = −0.220) were found, and positive expected correlations of LDL (r = 0.731), TC (r = 0.663), and TG (r = 0.584) with atheromatic index in the total studied sample were found. In conclusion, patients with a dyslipidemic profile should frequently check not only their lipid profile but also other biomarkers such as 25(OH)D, potassium, and oxidative stress markers to predict dyslipidemia and avoid subsequent disorders. Full article

The role of intestinal barrier homeostasis in an individual’s general well-being has been widely addressed by the scientific community. Colorectal cancer is among the illnesses that most affect this biological barrier. While chemotherapy is the first choice to treat this type of cancer, multidrug resistance (MDR) is the major setback against the commonly used drugs, with the ATP-binding cassette transporters (ABC transporters) being the major players. The role of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), or breast cancer resistance protein (ABCG2) in the efflux of chemotherapeutic drugs is well described in cancer cells, highlighting these proteins as interesting druggable targets to reverse MDR, decrease drug dosage, and consequently undesired toxicity. Natural products, especially phytochemicals, have a wide diversity of chemical structures, and some particular classes, such as phenolic acids, flavonoids, or pentacyclic triterpenoids, have been reported as inhibitors of P-gp, MRP1, and ABCG2, being able to sensitize cancer cells to chemotherapy drugs. Nevertheless, ABC transporters play a vital role in the cell’s defense against xenobiotics, and some phytochemicals have also been shown to induce the transporters’ activity. A balance must be obtained between xenobiotic efflux in non-tumor cells and bioaccumulation of chemotherapy drugs in cancer cells, in which ABC transporters are essential and natural products play a pivotal role that must be further analyzed. This review summarizes the knowledge concerning the nomenclature and function of ABC-transporters, emphasizing their role in the intestinal barrier cells. In addition, it also focuses on the role of natural products commonly found in food products, e.g., phytochemicals, as modulators of ABC-transporter activity and expression, which are promising nutraceutical molecules to formulate new drug combinations to overcome multidrug resistance. Full article

The current study emphasizes fungi as an important tool against heavy metals and how isolated fungal species can be used to create a successful strategy for the bioremediation of chromium and arsenic-contaminated sites/soils. Globally, heavy metal pollution is a serious issue. In the current investigation, contaminated sites were chosen, and samples could be taken from various localities of Hisar (29.1492° N, 75.7217° E) and Panipat (29.3909° N, 76.9635° E), India. A total of 19 fungal isolates were obtained from the collected samples through the enrichment culture technique using PDA media supplemented with Cr as chromic chloride hexahydrate (50 mg/L) and As as sodium arsenate (10 mg/L) and the potential of fungal isolates to be used for the removal of heavy metals was examined. The isolates were screened for minimum inhibitory concentrations (MIC) exhibiting tolerance capabilities, and the four best isolates C1, C3, A2, and A6 with the highest MICs (>5000 mg/L), were chosen for further investigations. To use the chosen isolates in the remediation of heavy metals (Cr and As), the culture conditions were optimized. The fungal isolates C1 and C3 estimated the highest removal of 58.60% and 57.00% at 50 mg/L chromium concentration, while the isolates A6 and A2 recorded the highest removal efficiency of 80% and 56% at 10 mg/L arsenic concentration under optimal conditions. Finally, the chosen fungal isolates C1 and A6 were molecularly identified as Aspergillus tamarii and Aspergillus ustus, respectively. Full article

Isometamidium chloride (ISM) is a trypanocide for the prophylactic and therapeutic use against vector-borne animal trypanosomosis (mainly Surra caused by Trypanosoma evansi) and African animal trypanosomosis caused by T. congolense/T. vivax/T. brucei). ISM was found to be an efficient trypanocide for therapeutic/prophylactic use against trypanosomosis; however, it produces some local and systemic detrimental effects in animals. We synthesized isometamidium chloride-loaded alginate gum acacia nanoformulation (ISM SANPS) to lessen the detrimental side effects of isometamidium chloride (ISM) while treating trypanosomal diseases. We intended to determine the cytocompatibility/toxicity, and DNA deterioration/chromosomal structural or number changes (genotoxicity) of ISM SANPs using mammalian cells in a concentration-dependent manner. Apurinic/apyrimidinic (AP) sites are one of the major types of DNA lesions formed during base excision and repair of oxidized, deaminated, or alkylated bases. The intensity of the cellular AP site is an excellent marker of the deterioration of DNA quality. We thought it pertinent to quantify the AP sites in ISM SANPs-treated cells. Our investigations established a dose-dependent cyto-compatibility or toxicity and DNA impairment (genotoxicity) in ISM SANPs-treated horse peripheral blood mononuclear cells. ISM SANPs were biocompatible at various concentrations tested on the mammalian cells. Full article