Antimicrobial photodynamic therapy against Escherichia coli by exploiting endogenously produced Protoporphyrin IX- In vitro study.

Due to antimicrobial drug resistance, there is a growing interest in the development of light based alternative antibacterial therapies. This research work is focused on the inactivation of Escherichia coli (E. coli) by exploiting the absorption bands 405, 505, 542, 580 and 631 nm of its indigenously produced Protoporphyrin IX (PpIX) excited by three LEDs with broad emission bands at 418, 522 and 630 nm and two laser diodes with narrow emission bands at 405 and 635 nm. Fluorescence spectroscopy and plate count method have been employed for studying the inactivation rate of E. coli strain in autoclaved water suspension. It has been found that LEDs at 418, 522 and 630 nm produced pronounced antimicrobial photodynamic effect on E. coli strain comparing laser diodes at 405 and 635 nm, which might be attributed to the overlapping of broad emission bands of LEDs with the absorption bands of PpIX than narrow emission bands of laser diodes. Particular effect of LED at 522 nm has been noticed because its broad emission band overlaps three absorption bands 505, 542 and 580 nm of PpIX. The gold standard plate count method strongly correlates with Fluorescence spectroscopy, making it an innovative tool to administer bacterial inactivation. The experimental results suggested the development of a light source that entirely overlap absorption bands of PpIx to produce a pronounced antimicrobial photodynamic effect, which might become an effective modality for in vivo disinfection of antibiotic resistant microbes in wounds and lesions.

Hyperhomocysteinemia in a Patient With Subdural Hematoma and Subarachnoid Hemorrhage Secondary to a Traumatic Brain Injury.

Traumatic brain injury (TBI) is a significant global health issue, contributing substantially to mortality and disability. Serum biomarkers, such as homocysteine (Hcy), play a critical role in the prognosis of brain injuries, with hyperhomocysteinemia (HHcy) potentially leading to neurological disorders. We present the case of a 64-year-old patient admitted to the emergency department following a road traffic accident (RTA). Magnetic resonance imaging (MRI) revealed parietal subdural hematoma (SDH), right frontal contusion, and left subarachnoid hemorrhage (SAH). The patient underwent a craniotomy to address SAH and SDH. Initial Hcy levels were markedly elevated compared to post-operative levels. Hcy represents a rapid, non-invasive, and cost-effective diagnostic tool for assessing brain injury severity and guiding medical intervention. Early detection of HHcy could potentially mitigate vascular and neurological complications, thereby improving patient outcomes.

Spatiotemporal analysis and clinico-epidemiological study for seroprevalence of canine leptospirosis.

Leptospirosis is a worldwide re-emerging zoonotic disease. The study was conducted to estimate the Seroprevalence of canine leptospirosis in a total of 450 dogs, from a total of 97 puppies and 353 adult dogs selected for examination Sampling, started from January to December 2023 in District Kasur in the province Punjab of the country Pakistan. Leptospira IgG ELISA kit manufactured by DRG Instruments GmbH, Germany was used for the screening of canine Leptospira antibodies. Out of 450 tested dogs, 183 dogs (40.67%) were tested positive for Leptospira antibody for the screening of Leptospira antibodies. The estimated Seroprevalence of leptospirosis in various age groups of dogs, were 23.7% (23/97) and 45.3% (160/353), in puppies and adults, respectively (P < 0.05). It was found that out of the sampled dogs, a total of 35/127 (27.6%), 29/100 (29%), 73/130 (56.2%), and 46/93 (49.5%) dogs were tested seropositive for Leptospira antibodies in winter, spring, summer and fall, respectively (P < 0.05).

Curcumin-loaded soluplus® based ternary solid dispersions with enhanced solubility, dissolution and antibacterial, antioxidant, anti-inflammatory activities.

Amorphous solid dispersion (ASD) has emerged to be an outstanding strategy among multiple options available for improving solubility and consequently biological activity. Interestingly several binary SD systems continue to exhibit insufficient solubility over time. Therefore, the goal of current research was to design ternary amorphous solid dispersions (ASDs) of hydrophobic model drug curcumin (CUR) to enhance the solubility and dissolution rate in turn, presenting enhanced anti-bacterial, antioxidant and anti-inflammatory activity. For this purpose several ternary solid dispersions (TSDs) consisting of Soluplus®, Syloid® XDP 3150, Syloid® 244 and Poloxamer® 188 in combination with HPMC E5 (binary carrier) were prepared using solvent evaporation method. Both solubility and dissolution testing of prepared solid dispersion were performed to determine the increase in solubility and dissolution. Solid state investigation was carried out utilizing infrared spectroscopy, also known as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM),Differential scanning calorimetry (DSC) and X-ray diffraction (XRD).Optimized formulations were also tested for their biological effectiveness including anti-bacterial, anti-oxidant and anti-inflammatory activity. Amid all Ternary formulations F3 entailing 20 % soluplus® remarkably improved the solubility (186 µg/ml ± 3.95) and consequently dissolution (91 % ± 3.89 %) of curcumin by 3100 and 9 fold respectively. These finding were also supported by FTIR, SEM, XRD and DSC. In-vitro antibacterial investigation of F3 also demonstrated significant improvement in antibacterial activity against both gram positive (Staphylococcus aureus, Bacillus cereus) and gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria. Among all the tested strains Staphylococcus aureus was found to be most susceptible with a zone of inhibition of 24 mm ± 2.87. Antioxidant activity of F3 was also notably enhanced (93 % ± 5.30) in contrast to CUR (69 % ± 4.79). In vitro anti-inflammatory assessment also exhibited that F3 markedly protected BSA (bovine serum albumin) from denaturation with percent BSA inhibition of 80 % ± 3.16 in comparison to CUR (49 % ± 2.91). Hence, F3 could be an effective solid dispersion system for the delivery of model hydrophobic drug curcumin.

Selenium improved arsenic toxicity tolerance in two bell pepper (Capsicum annuum L.) varieties by modulating growth, ion uptake, photosynthesis, and antioxidant profile.

Bell pepper (Capsicum annuum L.); an important spice crop of the region is a rich source of vitamins and antioxidants having many health benefits. Many biotic and abiotic factors contribute towards growth and yield losses of this crop. Arsenic (As) toxicity is a global issue, but it is particularly critical in developing countries. The current study was designed to evaluate the efficacy of selenium (Se) in mitigating the toxic effects of As in two varieties (HSP-181 A and PS09979325) of Capsicum annuum L. Different concentrations of As (0, 50, and 100 µM) and Se (0, 5, and 10 µM) were tested using 14 days old seedlings of C. annuum L. The As stress caused a significant (P ≤ 0.001) reduction in growth, uptake of nutrients, and eco-physiological attributes in both varieties however, the response was specific. While the overproduction of osmo-protectants and antioxidants intensified the symptoms of oxidative stress. The maximum reduction in shoot length (45%), fresh weight (29%), and dry weight (36%) was observed in under 100 µM As stress. The organic acids exudation from the roots of both cultivars were significantly increased with the increase in As toxicity. The Se treatment significantly (p ≤ 0.001) improved growth, nutrient uptake, gas exchange attributes, antioxidant production, while decreased oxidative stress indicators, and As uptake in the roots and shoots of all the subjects under investigation. It is concluded from the results of this study that Se application increased photosynthetic efficiency and antioxidant activity while decreasing As levels, organic acid exudation, and oxidative stress indicators in plants. Overall, the var. PS09979325 performed better and may be a good candidate for future pepper breeding program.

DFT, GC-MS analysis and biological evaluation of Limbarda crithmoides L. Dumort essential oil; an important edible halophyte grown in Pakistan.

Antimicrobial resistance is a major health burden in Pakistan, and therefore new herbal medicine-based therapeutic regimens are being largely investigated. Limbarda crithmoides essential oil was extracted by using hydrodistillation method. Chemical profiling of essential was evaluated by using FTIR and GC-MS analysis. A total of 20 components were identified including, p-xylene, o-xylene, ß-linalool, acetophenole and 3-isopropylphenyl methylcarbamate. The HOMO and LUMO analysis in DFT investigations presented that 3-isopropylphenyl methylcarbamate, p-xylene and o-xylene posess a substantial capacity to transfer charge through molecules. The antimicrobial potential of essential oil showed moderate inhibition against E. coli (MIC = 6.25 mg/mL), whereras a significant inhibition Staphylococos aureus was recorded (MIC = 3.12 mg/mL). Further, significant antioxidant activities were recorded in DPPH radical scavenging (IC50 = 80.5 µg/mL), H2O2 (64 ± 1.2%) and FRAP (60.3 µg ferrous equivalents) assays. It was therefore concluded that Limbarda crithmoides essential oil has potential antioxidant and anti-antimicrobial properties and can be used for further investigations.

Unrivalled insight into possible biopharmaceutical application of Justicia vahlii Roth. (Acanthaceae).: Chemodiversity, in vitro bioactivities, and computational analysis.

Justicia vahliiRoth. is an important wild medicinal food plant traditionally used for treating inflammation and various common ailments. This study investigated the chemical composition,antioxidant, enzyme inhibition and toxicity profiles of n-hexane (nHEJv) and chloroform (CEJv) extracts of J. vahlii. Moreover, the effect of the extracts was evaluated on CCl4 induced liver injury. The total phenolic and flavonoid contents were present in both extracts in significant amount. The UPLC-Q-TOF-MS and GC-MS profiling of CEJv tentatively identified several important phytocompounds. The CEJv extract was comparatively more active for antioxidant activity and α-amylase inhibition, whereas the nHEJv extract presented higher inhibition potential against urease, tyrosinase, and α-glucosidase enzymes. Similarly, the in-silico study of four major compounds, i.e., 1-acetoxypinoresinol, 3-hydroxysebacic acid, nortrachelogenin, and viscidulin-III have shown a good docking score against the clinically significant enzymes. The acute oral toxicity and brine shrimp lethality assaysrevealed the extracts as non-toxic. The CCl4 treated animals showed a geared depletion of various antioxidant enzymes which were significantly reversed with the treatment of the extracts. Overall, the study's findings revealed J. vahliiwith antioxidant mediated hepatoprotective and enzyme inhibition potential and warrant further research on isolation of the bioactive compounds.

Microbiome analysis reveals alteration in water microbial communities due to livestock activities.

The Baihe River, a tributary of the Yellow River located in the Ngawa Tibetan and Qiang Autonomous Prefecture in Northern Sichuan, is surrounded by natural resources suitable for animal development. However, the impact of livestock activities water microbiome in this area remains unexplored. This study collected water samples from areas with captive yaks and sheep (NS and YS) and compared them with water samples from Hongyuan Baihe River. Through amplicon sequencing, we investigated the impact of livestock activities on aquatic microorganisms. Diversity analysis, significance analysis, and microbial phenotype prediction indicated a significant decrease in microbial community diversity and function in the NS and YS groups. Pathogenic microorganisms such as Bacteroidales and Thelebolaceae and antibiotic-resistant bacteria genes such as Flavobacteriales and Burkholderiaceae were significantly higher in livestock breeding areas. Additionally, bacteria adapted to acidification, hypoxia, and eutrophication (e.g., Acidobacteria, Flavobacteriales, Deltaproteobacteria, Rhodobacterales) were more abundant in these areas. Our results demonstrate that livestock activities significantly alter the structure and function of microbial communities in surrounding water bodies, deteriorating water quality.

Fractional order cancer model infection in human with CD8+ T cells and anti-PD-L1 therapy: simulations and control strategy.

In order to comprehend the dynamics of disease propagation within a society, mathematical formulations are essential. The purpose of this work is to investigate the diagnosis and treatment of lung cancer in persons with weakened immune systems by introducing cytokines ( I L 2 & I L 12 ) and anti-PD-L1 inhibitors. To find the stable position of a recently built system TCD I L 2 I L 12 Z, a qualitative and quantitative analysis are taken under sensitive parameters. Reliable bounded findings are ensured by examining the generated system's boundedness, positivity, uniqueness, and local stability analysis, which are the crucial characteristics of epidemic models. The positive solutions with linear growth are shown to be verified by the global derivative, and the rate of impact across every sub-compartment is determined using Lipschitz criteria. Using Lyapunov functions with first derivative, the system's global stability is examined in order to evaluate the combined effects of cytokines and anti-PD-L1 inhibitors on people with weakened immune systems. Reliability is achieved by employing the Mittag-Leffler kernel in conjunction with a fractal-fractional operator because FFO provide continuous monitoring of lung cancer in multidimensional way. The symptomatic and asymptomatic effects of lung cancer sickness are investigated using simulations in order to validate the relationship between anti-PD-L1 inhibitors, cytokines, and the immune system. Also, identify the actual state of lung cancer control with early diagnosis and therapy by introducing cytokines and anti-PD-L1 inhibitors, which aid in the patients' production of anti-cancer cells. Investigating the transmission of illness and creating control methods based on our validated results will both benefit from this kind of research.

Ventricular Fibrillation Arrest Triggered by Antiemetics Revealing an Underlying Long QT Syndrome in a Young Woman.

Undiagnosed phenomena such as long QT syndrome can have devastating effects on patients. Our case, involving a woman in her 30s, highlights the serious effects of undiagnosed long QT and how antiemetic medications can precipitate cardiac events that can lead to fatalities. Various medications are known to prolong QT intervals, and clinicians must be aware of the side effects of some of these commonly used medications. While survival was achieved in this case, education and reflection can act as a tool to help improve global standards of care in this subgroup of the population.

Cellulose ether and carbopol 971 based gastroretentive controlled release formulation design, optimization and physiologically based pharmacokinetic modeling of ondansetron hydrochloride minitablets.

This study aims to design and optimize ondansetron (OND) gastro-retentive floating minitablets for better and prolonged control of postoperative nausea and vomiting (PONV) with improved patient compliance. Minitablets were directly compressed and encapsulated in a size 2 capsule shell with an overall dose of 24 mg. Central composite design (CCD) was applied keeping one cellulose ether derivative HPMC K15M and Carbopol 971 as variable and used as swelling and rate retarding agents. The other cellulose derivative i.e. sodium carboxymethyl cellulose, along with mannitol, sodium bicarbonate, and talc, were used in fixed quantities. The floating lag time, total floating time, swelling index, in-vitro drug release, and zero-order (RSQ value), were critical quality parameters. The optimized formulation (Fpred) was evaluated for all critical parameters, along with surface morphology, thermal stability, chemical interaction, and accelerated stability. The in silico PBPK modeling was applied to compare the bioavailability of Fpred with reference OND immediate-release tablets. The numerical optimization model predicted >90 % drug release with zero-order at 12 h. In silico PBPK modeling revealed comparable relative bioavailability of Fpred with the reference formulation. The gastroretentive floating minitablets of OND were successfully designed for prolonged emesis control in patients receiving chemotherapeutic agents.

Synthesis, Invitro Cytotoxic Activity and Optical Analysis of Substituted Schiff Base Derivatives.

Fluorescent cytotoxic compounds with readout delivery are crucial in chemotherapy. The growing demands of these treatment strategies require the novel heterocyclic molecules with better selectivity alongside fluorescence marker potential. In this context, a series of nine isatin Schiff base derivatives 4a-i were synthesized, characterized and evaluated for UV-visible, fluorescence, thermal and bioanalysis in order to explore the effect of structure on their bioprofiles. The analogue 4d exhibited maximum cytotoxic activity on Hella cells with percentage inhibition of 83% at 50 µM and 100% at 150 µM concentrations while 4c showed minimum cytotoxic activity with the value of 19% at 50 µM and 22% at 150 µM concentrations. Meanwhile, 4g was found to exhibit maximum inhibition potential towards Vero Cells with the percentage inhibition values of 83 at 50 µM concentration. The overall SAR study showed that the para-fluoro-substituted isatin moieties exhibited the appreciable percentage inhibition while the least activity was delivered by the isatin derivatives with para-bromo substitution.

Influence of Fungicide Application on Rhizosphere Microbiota Structure and Microbial Secreted Enzymes in Diverse Cannabinoid-Rich Hemp Cultivars.

Microbes and enzymes play essential roles in soil and plant rhizosphere ecosystem functioning. However, fungicides and plant root secretions may impact the diversity and abundance of microbiota structure and enzymatic activities in the plant rhizosphere. In this study, we analyzed soil samples from the rhizosphere of four cannabinoid-rich hemp (Cannabis sativa) cultivars (Otto II, BaOx, Cherry Citrus, and Wife) subjected to three different treatments (natural infection, fungal inoculation, and fungicide treatment). DNA was extracted from the soil samples, 16S rDNA was sequenced, and data were analyzed for diversity and abundance among different fungicide treatments and hemp cultivars. Fungicide treatment significantly impacted the diversity and abundance of the hemp rhizosphere microbiota structure, and it substantially increased the abundance of the phyla Archaea and Rokubacteria. However, the abundances of the phyla Pseudomonadota and Gemmatimonadetes were substantially decreased in treatments with fungicides compared to those without fungicides in the four hemp cultivars. In addition, the diversity and abundance of the rhizosphere microbiota structure were influenced by hemp cultivars. The influence of Cherry Citrus on the diversity and abundance of the hemp rhizosphere microbiota structure was less compared to the other three hemp cultivars (Otto II, BaOx, and Wife). Moreover, fungicide treatment affected enzymatic activities in the hemp rhizosphere. The application of fungicides significantly decreased enzyme abundance in the rhizosphere of all four hemp cultivars. Enzymes such as dehydrogenase, dioxygenase, hydrolase, transferase, oxidase, carboxylase, and peptidase significantly decreased in all the four hemp rhizosphere treated with fungicides compared to those not treated. These enzymes may be involved in the function of metabolizing organic matter and degrading xenobiotics. The ecological significance of these findings lies in the recognition that fungicides impact enzymes, microbiota structure, and the overall ecosystem within the hemp rhizosphere.

Recent progress in electro-Fenton technology for the remediation of pharmaceutical compounds in aqueous environments.

The global focus on wastewater treatment has intensified in the contemporary era due to its significant environmental and human health impacts. Pharmaceutical compounds (PCs) have become an emerging concern among various pollutants, as they resist conventional treatment methods and pose a severe environmental threat. Advanced oxidation processes (AOPs) emerge as a potent and environmentally benign approach for treating recalcitrant pharmaceuticals. To address the shortcomings of traditional treatment methods, a technology known as the electro-Fenton (EF) method has been developed more recently as an electrochemical advanced oxidation process (EAOP) that connects electrochemistry to the chemical Fenton process. It has shown effective in treating a variety of pharmaceutically active compounds and actual wastewaters. By producing H2O2 in situ through a two-electron reduction of dissolved O2 on an appropriate cathode, the EF process maximizes the benefits of electrochemistry. Herein, we have critically reviewed the application of the EF process, encompassing diverse reactor types and configurations, the underlying mechanisms involved in the degradation of pharmaceuticals and other emerging contaminants (ECs), and the impact of electrode materials on the process. The review also addresses the factors influencing the efficiency of the EF process, such as (i) pH, (ii) current density, (iii) H2O2 concentration, (iv) and others, while providing insight into the scalability potential of EF technology and its commercialization on a global scale. The review delves into future perspectives and implications concerning the ongoing challenges encountered in the operation of the electro-Fenton process for the treatment of PCs and other ECs.

Breathing in danger: Understanding the multifaceted impact of air pollution on health impacts.

Air pollution, a pervasive environmental threat that spans urban and rural landscapes alike, poses significant risks to human health, exacerbating respiratory conditions, triggering cardiovascular problems, and contributing to a myriad of other health complications across diverse populations worldwide. This article delves into the multifarious impacts of air pollution, utilizing cutting-edge research methodologies and big data analytics to offer a comprehensive overview. It highlights the emergence of new pollutants, their sources, and characteristics, thereby broadening our understanding of contemporary air quality challenges. The detrimental health effects of air pollution are examined thoroughly, emphasizing both short-term and long-term impacts. Particularly vulnerable populations are identified, underscoring the need for targeted health risk assessments and interventions. The article presents an in-depth analysis of the global disease burden attributable to air pollution, offering a comparative perspective that illuminates the varying impacts across different regions. Furthermore, it addresses the economic ramifications of air pollution, quantifying health and economic losses, and discusses the implications for public policy and health care systems. Innovative air pollution intervention measures are explored, including case studies demonstrating their effectiveness. The paper also brings to light recent discoveries and insights in the field, setting the stage for future research directions. It calls for international cooperation in tackling air pollution and underscores the crucial role of public awareness and education in mitigating its impacts. This comprehensive exploration serves not only as a scientific discourse but also as a clarion call for action against the invisible but insidious threat of air pollution, making it a vital read for researchers, policymakers, and the general public.

Advances in organocatalyzed synthesis of organic compounds.

The recent advancements in utilizing organocatalysts for the synthesis of organic compounds have been described in this review by focusing on their simplicity, effectiveness, reproducibility, and high selectivity which lead to excellent product yields. The organocatalytic methods for various derivatives, such as indoles, pyrazolones, anthrone-functionalized benzylic amines, maleimide, polyester, phthalimides, dihydropyrimidin, heteroaryls, N-aryl benzimidazoles, stilbenoids, quinazolines, quinolines, and oxazolidinones have been specifically focused. The review provides more understanding by delving into potential reaction mechanisms. We anticipate that this collection of data and findings on successful synthesis of diverse compound derivatives will serve as valuable resources and stimulating current and future research efforts in organocatalysis and industrial chemistry.

Heavy Metal(oid)s Contamination and Potential Ecological Risk Assessment in Agricultural Soils.

Soil pollution caused by heavy metal(oid)s has generated great concern worldwide due to their toxicity, persistence, and bio-accumulation properties. To assess the baseline data, the heavy metal(oid)s, including manganese (Mn), iron (Fe), Cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), lead (Pb), mercury (Hg), chromium (Cr), and cadmium (Cd), were evaluated in surface soil samples collected from the farmlands of Grand Forks County, North Dakota. Samples were digested via acid mixture and analyzed via inductively coupled plasma mass spectrometry (ICP MS) analysis to assess the levels, ecological risks, and possible sources. The heavy metal(oid) median levels exhibited the following decreasing trend: Fe > Mn > Zn > Ni > Cr > Cu > Pb > Co > As > Cd > Hg. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) suggested the main lithogenic source for the studied metal(oid)s. Metal(oid) levels in the current investigation, except Mn, are lower than most of the guideline values set by international agencies. The contamination factor (Cf), geo accumulation index (Igeo) and enrichment factor (EF) showed considerable contamination, moderate contamination, and significant enrichment, respectively, for As and Cd on median value basis. Ecological risk factor (Er) results exhibited low ecological risk for all studied metal(oid)s except Cd, which showed considerable ecological risk. The potential ecological risk index (PERI) levels indicated low ecological risk to considerable risk. Overall, the results indicate the accumulation of As and Cd in the study area. The high nutrients of the soils potentially affect their accumulation in crops and impact on consumers' health. This drives the impetus for continued environmental monitoring programs.

Corrigendum: Sesquiterpene lactones attenuate paclitaxel resistance via inhibiting MALAT1/STAT3/ FUT4 axis and P-Glycoprotein transporters in lung cancer cells.

[This corrects the article DOI: 10.3389/fphar.2022.795613.].

Evaluation of genotoxic effect via expression of DNA damage responsive gene induced by ivermectin on MDBK cell line.

Ivermectin (IVM) is an anti-parasitic drug which is used for treating parasitic infestations. It has been used in humans for treating intestinal strongyloidiasis and onchocerciasis however, currently researchers are investigating its potential for treating coronavirus SARS-CoV-2. Due to its broad-spectrum activities, IVM is being used excessively in animals which has generated an interest for researchers to investigate its toxic effects. Cytotoxic and genotoxic effects have been reported in animals due to excessive usage of IVM. Therefore, this study aims to evaluate the cytotoxic and genotoxic effects of IVM on the Madin-Darby-Bovine-Kidney (MDBK) cell line by examining the expression of a DNA damage-responsive gene (OGG1). Cytotoxicity of IVM was tested using an assay (MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), whereas the genotoxicity was evaluated using comet assay along with micronucleus assay. Moreover, the gene expression of DNA damage response gene (OGG1) was measured by qRT-PCR, after extraction of RNA from the MDBK cell line using the TRIzol method and its conversion to cDNA by reverse-transcriptase PCR. During the experiment, cell viability percentage was measured at different doses of IVM i.e., 25%, 50%, 75%, along with LC50/2, LC50 and LC50*2. It was observed that the gene expression of OGG1 increased as the concentration of IVM increased. It was concluded that IVM has both cytotoxic and genotoxic effects on the MDBK cell line. Furthermore, it is recommended that studies related to the toxic effects of IVM at molecular level and on other model organisms should be conducted to combat its hazardous effects.