Medicinal plants show remarkable antiproliferative potential in human cancer cell lines.

Molecules isolated and identified from plant origin are used to manufacture most chemotherapeutic drugs for cancer treatment. We assumed that these plant extracts contain prolific bioactive compounds with potent antiproliferative activities and could be effective against different human cancer cells. Ethanolic extracts were prepared from Chelidonium majus, Myrica cerifera, Fumaria indica, Nigella sativa, and Silybum marianum, and the antiproliferative assay was performed in HepG2 and HeLa human cancer cell lines. All plants extract exhibited antiproliferative potential against studied cancer cell lines in the dose and time-dependent manner. Chelidonium majus and Silybum marianum have shown promising results against HepG2 and HeLa cells, respectively, followed by Myrica cerifera, Fumaria indica, and Nigella sativa. Results indicated that utilization of whole plant extract as anticancer compounds could be of great value in generating novel chemotherapeutic drugs.

Isolation and characterization of phytochemicals from ethyl acetate fraction of Solanum nigrum using GC-MS.

Solanum nigrum plant has rich therapeutic potential and different developed countries utilize this plant as a chief element for oriental medicinal practice including cancer therapy. The current study determines the isolation and purification of S. nigrum bioactive constituents through column chromatography from ethyl acetate extract of the plant followed by the Gas Chromatography-Mass Spectroscopy (GC-MS) to analyze the isolated compounds Different gradient elutions followed by thin layer chromatography of collected fractions were done and structural analysis of the isolated compounds was performed following GCMS analysis, More specifically the compounds were identified as 1, 2 benzene dicarboxylic acid, diisooctyl ester (95%) and as Bis (2-Ethylhexyl) phthalate (84%) along with 3 hydroxy 4 carboxy 2 methyl 6 pyridine (58%) with reference to chemical abstract service which may be responsible for its pharmacological properties. According to the best information available, no documented information exists regarding GC-MS based identification of the isolated chemical compounds from the S. nigrum. Present findings will help in exploring the therapeutic potential of 1, 2 benzene dicarboxylic acid, diisooctyl ester (95%), Bis (2-Ethylhexyl) phthalate (84%) and 3 hydroxy 4 carboxy 2 methyl 6 pyridine (58%) will be helpful in the development of new composites in pharmaceutical fields.

Naringin: Cardioprotective properties and safety profile in diabetes treatment.

Flavonoids derived from plants offer a broad spectrum of therapeutic potential for addressing metabolic syndrome, particularly diabetes mellitus (DM), a prevalent non-communicable disease. Hyperglycemia in DM is a known risk factor for cardiovascular diseases (CVDs), which substantially impact global mortality rates. This review examines the potential effects of naringin, a citrus flavonoid, on both DM and its associated cardiovascular complications, including conditions like diabetic cardiomyopathy. The safety profile of naringin is summarized based on various pre-clinical studies. The data for this review was gathered from diverse electronic databases, including Medline, PubMed, ScienceDirect, SpringerLink, Google Scholar, and Emerald Insight. Multiple pre-clinical studies have demonstrated that naringin exerts hypoglycemic and cardioprotective effects by targeting various vascular mechanisms. Specifically, research indicates that naringin down-regulates the renin-angiotensin and oxidative stress systems while concurrently upregulating ß-cell and immune system functions. Clinical trial outcomes also support the therapeutic potential of naringin in managing hyperglycemic states and associated cardiovascular issues. Moreover, toxicity studies have confirmed the safety of naringin in animal models, suggesting its potential for safe administration in humans. In conclusion, naringin emerges as a promising natural candidate for both antidiabetic and cardioprotective purposes, offering potential improvements in health outcomes. While naringin presents a new avenue for therapies targeting DM and CVDs, additional controlled and long-term clinical trials are necessary to validate its efficacy and safety for human use.

Evaluation of Hematological, Oxidative Stress, and Antioxidant Profile in Cattle Infected with Brucellosis in Southern Punjab, Pakistan.

Brucellosis is a well-known and harmful zoonotic disease that poses a severe threat to public health and wild and dairy animals. Due to a lack of monitoring and awareness, disease incidence has increased. Therefore, this study was conducted for the first time to ascertain the status of seroprevalence of brucellosis, hematological, oxidative stress, and antioxidant enzymes in different breeds of cattle reared under tropical-desert conditions in Pakistan. This study comprised 570 cattle of different breeds. We recorded some epidemiological traits, including age and gender. The blood samples were obtained from all the cattle, screened with RBPT, and then confirmed by ELISA and PCR. The results recorded an overall 11.75%, 10.7%, and 9.64% prevalence of brucellosis based on RBPT, ELISA, and PCR. We obtained nonsignificant results in different age and sex groups of cattle. The results showed significantly (P ≤ 0.05) lower values of erythrocyte counts, hemoglobin quantity, hematocrit, lymphocytes, and monocytes in infected cases. The results showed that the total leukocyte and neutrophil cells significantly (P ≤ 0.05) increased. The lipid peroxidation parameters (MDA- and NO-scavenging activity of erythrocyte) increased significantly (P ≤ 0.05) in infected cattle, whereas significantly reduced antioxidant enzymes like SOD, RGSH, and CAT were. Similarly, significantly lower serum albumin levels and total serum proteins were recorded in infected cattle.

Exploration of ACE-Inhibiting Peptides Encrypted in Artemisia annua Using In Silico Approach.

The renin-angiotensin system (RAS) is involved in body fluid regulation, but one of its enzymes, angiotensin-converting enzyme (ACE), indirectly causes hypertension by constricting blood vessels. Autoimmune illness is linked to the increased risk of hypertension and cardiovascular disease. In this study, ACE-inhibiting peptides were studied from Artemisia annua proteins. In silico hydrolysis of proteins was performed by BIOPEP-UWM using proteolytic enzymes from plant, microbial, and digestive sources. The physicochemical properties of 1160 peptides were determined using the peptide package of R studio. Di- and tripeptides were mostly released with a molecular weight of 170 to 350 Da. PeptideRanker was used to select 16 peptides from a pool of 1160 peptides based on their likelihood of being bioactive. Molecular docking was performed by DS 2020 and AutoDock Vina, which revealed that the stability of the ligand-receptor complex is due to hydrogen bonding and electrostatic and hydrophobic interactions. Their binding energies ranged from -31.81 to -20.09 kJ/mol. For drug-likeness evaluation, an online tool SwissADME was used that follows the ADME rule (absorption, distribution, metabolism, and excretion) to check the pharmacokinetics and drug-likeness of the compound. In the future, the released peptides can be used to make functional nutraceutical foods against hypertension.

Histopathological Investigations and Molecular Confirmation Reveal Mycobacterium bovis in One-Horned Rhinoceros (Rhinoceros unicorns).

Mycobacterium bovis causes tuberculosis in dairy and wild animals. Presence of tuberculosis in animals poses a threat not only to their herd mates but also for public. No reports are available about the clinical, pathological, and molecular investigation of naturally occurring tuberculosis (TB) due to M. bovis in one-horned rhinoceros. One-horned female rhinoceros (Rhinoceros unicorns) at the age of 41 years died in a public park in Pakistan. Postmortem and other investigations were carried out to know the cause of death. The present study describes necropsy, histopathology, and molecular-based confirmation of TB in a captive female rhinoceros that died of this infection. Clinically, the rhinoceros showed nonspecific clinical signs including anorexia, lethargy, dyspnoea, coughing, and sudden death. At necropsy, the trachea exhibited mild congestion and contained catarrhal exudate at the bronchial bifurcation. Macroscopic examination revealed characteristic tubercles on all parenchymatous organs. The lungs showed consolidation, grey hepatization, and contained granulomatous lesions packed with cheesy exudate. Histopathological examination showed severe pneumonic changes in the form of granulomatous inflammation consisting of lymphocytes, multinucleated giant cells, caseous materials, and mineralized foci surrounded by a fibrous capsule. PCR amplicon of 500 bp confirmed the presence of M. bovis in multiple hepatic and pulmonary tissue samples, as well as in uterine exudates. It was concluded that the presence of tuberculosis in rhinoceros may pose potential transmission risk to other animals and the application of practical tools to determine TB status in the rhinoceros is crucial.

Pathological, Histological, and Molecular Based Investigations Confirm Novel Mycobacterium bovis Infection in Boselaphus tragocamelus.

Mycobacterium bovis (M. bovis) being the main cause of animal tuberculosis is a complex infectious agent and can be a cause of zoonotic tuberculosis zoonosis in public health. To date, the uncommon infection in public health due to M. bovis still is a great challenge to both veterinary and medical professions and requires a careful diagnosis and confirmation of the bacterium. Therefore, this study for the first time reports the clinical, gross, histopathological, and molecular based confirmation of M. bovis infection in wildlife animals (nilgai). Prior to death, the morbid animal showed severe pneumonic ailments like moist cough, thick nasal exudates, and dyspnoea. At necropsy, enlargement of mandibular cervical and mesenteric lymph nodes was observed. Different macroscopic lesions such as congestion and hyperaemia, creamy white and catarrhal exudates in trachea, consolidation, grey and red hepatisation of lungs, and micro- and macrogranulomatous tubercles containing caseous materials in lungs were observed. The heart of morbid animal showed congestions, myocarditis, and a copious amount of straw-colored fluid in the pericardial sac. At the microscopic level, lungs indicated granulomatous inflammatory response, presence of multinucleated giant cells, fibrosis, and punctuation of alveoli with chronic inflammatory cells. Histopathological examination of various sections of the heart of the infected animal showed chronic inflammatory response consisting of chronic inflammatory cells like monocyte, lymphocytes, and fibroblasts along with noncalcified eosinophilic materials. At the molecular level, M. bovis infection was confirmed in various tissues like the heart, lungs, cervical, and mesenteric lymph nodes in morbid animals. In conclusion, based on our results, it can be suggested that more molecular based epidemiological studies are crucial to know the exact cause of pulmonary and cervical tuberculosis in wild animals.

Biologically Synthesized Copper Nanoparticles Show Considerable Degradation of Reactive Red 81 Dye: An Eco-Friendly Sustainable Approach.

Diospyros kaki leaf extract was used in this study as a favorable basis for the synthesis of copper nanoparticles (Cu NPs). X-ray diffraction (XRD) and UV-visible spectroscopy approaches were used to characterize the biologically synthesized copper nanoparticles. The XRD analysis showed that copper nanoparticles were face-centered cubic structure. Various experimental levels like conc. of dye, concentration of Cu NPs, pH, reaction time, and temperature were optimized to decolorize reactive red 81 dye using the synthesized Cu NPs. Reactive red 81 dye was decolorized maximum using Cu NPs of 0.005 mg/L. Additionally, reactive red 81 dye was decolorized at its maximum at pH = 6, temperature = 50°C. Our study reported that chemical oxidation demand (COD) and total organic carbon (TOC) deduction efficacies were 74.56% and 73.24%. Further degradation study of reactive red 81 dye was also carried out. Cu NPs have the ability and promising potential to decolorize and degrade reactive red 81 dye found in wastewater.

Biologically Synthesized Peptides Show Remarkable Inhibition Activity against Angiotensin-Converting Enzyme: A Promising Approach for Peptide Development against Autoimmune Diseases.

Angiotensin-converting enzyme (ACE) regulates several biological functions besides its vital role in immune functions. ACE is elevated in immune cells in inflammatory diseases including atherosclerosis, granuloma, chronic kidney disease, and also autoimmune diseases, like multiple sclerosis, rheumatoid arthritis, and type I diabetes. No significant information prevails in the literature regarding the isolation, identification, and profiling of potential ACE inhibitory peptides. In the present study, indigenous crop varieties like seeds (peanut, corn, oat, sunflower, chickpea, parsley, cottonseed, papaya, sesame, and flaxseed) were used to evaluate their ACE inhibition activity. Variables including hydrolysis time, enzyme-to-substrate ratio (E/S), pH, and temperature were standardized to acquire the most suitable and optimum ACE inhibition activity. Seeds of cotton, chickpea, and peanuts displayed remarkably maximum ACE inhibition activity than other plants. The study disclosed that maximum ACE inhibitory activity (86%) was evaluated from cottonseed at pH 8.0, temperature of 45°C, hydrolysis time of 2 hrs, and enzyme to the substrate (E/S) ratio of 1 : 5 followed by peanuts (76%) and chickpea (55%). SDS-PAGE confirmed that vicilin protein is present in cottonseed and peanut seed while cruciferin and napin proteins are present in chickpeas. LC-MS/MS analysis disclosed potential novel peptides in hydrolyzed cottonseed that can be ascribed as potential ACE inhibitors which have never been reported and studied earlier. The current study further showed that cottonseed peptides due to their promising ACE inhibitory activity can be a valuable source in the field of ACE inhibitor development.

Bisphenol A Induces Histopathological, Hematobiochemical Alterations, Oxidative Stress, and Genotoxicity in Common Carp (Cyprinus carpio L.).

Bisphenol A (BPA) is one of the environmental endocrine disrupting toxicants and is widely used in the industry involving plastics, polycarbonate, and epoxy resins. This study was designed to investigate the toxicological effects of BPA on hematology, serum biochemistry, and histopathology of different organs of common carp (Cyprinus carpio). A total of 60 fish were procured and haphazardly divided into four groups. Each experimental group contained 15 fish. The fish retained in group A was kept as the untreated control group. Three levels of BPA 3.0, 4.5, and 6 mg/L were given to groups B, C, and D for 30 days. Result indicated significant reduction in hemoglobin (Hb), lymphocytes, packed cell volume (PCV), red blood cells (RBC), and monocytes in a dose-dependent manner as compared to the control group. However, significantly higher values of leucocytes and neutrophils were observed in the treated groups (P < 0.05). Results on serum biochemistry revealed that the quantity of glucose, cholesterol, triglycerides, urea, and creatinine levels was significantly high (P < 0.05). Our study results showed significantly (P < 0.05) increase level of oxidative stress parameters like reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) and lower values of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) in treated groups (4.5 mg/L and 6 mg/L)) in the brain, liver, gills, and kidneys. Our study depicted significant changes in erythrocytes (pear shaped erythrocytes, leptocytes, microcytes, spherocytes, erythrocytes with broken, lobed, micronucleus, blabbed, vacuolated nucleus, and nuclear remnants) among treated groups (4.5 mg/L and 6 mg/L). Comet assay showed increased genotoxicity in different tissues including the brain, liver, gills, and kidneys in the treated fish group. Based on the results of our experiment, it can be concluded that the BPA exposure to aquatic environment is responsible for deterioration of fish health, performance leading to dysfunction of multiple vital organs.

Nuclear and Morphological Alterations in Erythrocytes, Antioxidant Enzymes, and Genetic Disparities Induced by Brackish Water in Mrigal Carp (Cirrhinus mrigala).

Salinization of aquatic ecosystem, abrupt climate change, and anthropogenic activities cause adverse impact on agricultural land/soil as well as the aquaculture industry. This experimental study was designed to evaluate different biomarkers of oxidative stress, antioxidant enzymes, and genotoxic potential of diverse salinities of brackish water on freshwater fish. A total of 84 fresh water mrigal carp (Cirrhinus mrigala) were randomly segregated and maintained in four groups (T0, T1, T2, and T3) in a glass aquarium under similar laboratory conditions at various salinity levels (0, 3, 5, and 7 parts per thousand) to determine the pathological influence of brackish water. All the fish in groups T1, T2, and T3 were exposed to various salinity levels of brackish water for a period of 90 days while the fish of group T0 served as the control group. The experimental fish reared in different groups T1, T2, and T3 displayed various physical and behavioral ailments. The results revealed significantly augmented quantity of different oxidative stress indicators including reactive oxygen species (ROS) and thiobarbituric acid reactive substance (TBARS) in different visceral tissues (kidneys, liver, and gills) of exposed fish. Different antioxidant enzymes such as reduced glutathione (GSH), peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) along with total proteins were remarkably reduced in the kidneys, gills, and liver tissues. Results showed significantly increased values of different nuclear abnormalities (erythrocyte with micronucleus, erythrocyte with condensed nucleus, and erythrocyte with lobed nucleus) and morphological changes (pear shaped erythrocyte, spindle-shaped erythrocytes, and spherocyte) in red blood cells of experimental fish. The results on genotoxic effects exhibited significantly increased DNA damage in isolated cells of liver, kidneys, and gills of exposed fish. The findings of our experimental research suggested that brackish water causes adverse toxicological impacts on different visceral tissues of fresh water fish at higher salinity level through disruption and disorder of physiological and biochemical markers.

In vitro cytotoxic potential of Solanum nigrum against human cancer cell lines.

Plants have natural products which use to possess antiproliferative potential against many cancers. In the present study, six isolated fractions (ethyl acetate, petroleum ether, chloroform, n-butanol, ethanol and aqueous) from Solanum nigrum were evaluated for their cytotoxic effect on different cell lines. Hepatic carcinoma cell line (HepG2), cervical cancer cell line (HeLa) and baby hamster kidney (BHK) used as normal non-cancerous cells were evaluated for cytotoxicity against isolated fractions. Cell viability assay was performed to evaluate the cytotoxicity of all fractions on different cell lines followed by the lactate dehydrogenase and vascular endothelial growth factor assays of most active fraction among all screened for cytotoxic analysis. HPLC analysis of most active fractions against cytotoxicity was performed to check the biological activity of compounds. Results displayed the potent cytotoxic activity of ethyl acetate fraction of S. nigrum against HepG2 cells with IC50 value of 7.89 µg/ml. Other fractions exhibited potent anticancer activity against HepG2 cells followed by HeLa cells. Fractions in our study showed no cytotoxicity in BHK cells. Cytotoxic activity observed in our current study exposed high antiproliferative potential and activity of ethyl acetate fraction against HepG2 cells. The results demonstrated that S. nigrum fractions exhibited anticancer activity against hepatic and cervical cancer cell lines with non-toxic effect in normal cells. These results reveal significant potential of S. nigrum for the therapeutic of cancers across the globe in future.

In Silico Structural, Functional, and Phylogenetic Analysis of Cytochrome (CYPD) Protein Family.

Cytochrome (CYP) enzymes catalyze the metabolic reactions of endogenous and exogenous compounds. The superfamily of enzymes is found across many organisms, regardless of type, except for plants. Information was gathered about CYP2D enzymes through protein sequences of humans and other organisms. The secondary structure was predicted using the SOPMA. The structural and functional study of human CYP2D was conducted using ProtParam, SOPMA, Predotar 1.03, SignalP, TMHMM 2.0, and ExPASy. Most animals shared five central motifs according to motif analysis results. The tertiary structure of human CYP2D, as well as other animal species, was predicted by Phyre2. Human CYP2D proteins are heavily conserved across organisms, according to the findings. This indicates that they are descended from a single ancestor. They calculate the ratio of alpha-helices to extended strands to beta sheets to random coils. Most of the enzymes are alpha-helix, but small amounts of the random coil were also found. The data were obtained to provide us with a better understanding of mammalian proteins' functions and evolutionary relationships.

Human Papillomavirus, MicroRNA and their Role in Cervical Cancer Progression, Diagnosis and Treatment Response: A Comprehensive Review.

Human Papillomavirus (HPV) is sexually transmitted and linked with vaginal, vulvar and cervix cancers in females, penile cancer in male, while anal and oropharyngeal cancer in both genders. Cervical cancer is ranked as third most identified cancer among females globally and is the fourth leading reason of cancer related mortality. The main aim of current study is to highlight the key role of miRNA in cervical cancer development, progression and their therapeutic responses. Current study entailed more than 50 PubMed cited articles related to miRNA role in cervical cancer. Studies have elucidated the role of miRNAs regulation in gene expression at post-transcriptional and translational level by targeting significant genes and therefore involved in cervical cancer. miRNAs control several cellular pathways involved in development of pre-malignant to metastatic stage and proliferation to malignancy. Current review elucidated and elaborated the key role of miRNA their application, treatment and therapeutic responses in cervical cancer.

Prevalence of Human Parvovirus B19 in Neurological Patients: Findings from Region of Western Saudi Arabia.

Human parvovirus (B19) infection causes Erythema infectiosum in persons with other hematological disorders like aplastic anemia and complications such as hydrops fetalis, spontaneous abortions. This study aimed to determine the prevalence of IgG and IgM antibodies in B19 infected neurological patients and to assess possible transmission related risk factors. This cross-sectional descriptive study comprised 140 neurological patients. Blood samples were screened for both IgG and IgM against B19 by ELISA and nested PCR. IgG and IgM accounted 6.4% and 3.5% prevalence in neurological patients. Both IgG and IgM revealed prevalence of 3.5% simultaneously in different age groups. IgG and IGM Nested PCR displayed 6.42% B19 viral DNA prevalence among samples analyzed. Among B19 risk associated factors, only history of blood transfusion (Odds Ratio=1.9:1, P=0.04) was significantly associated with B19 infection among neurological patients. Neurological patients showed very less prevalence of B19 infection and hence disclose no significant association on risk factors associated with its transmission.

In Silico Study of Protein-Protein Interactions in Mapks and pp2cs of Medicago sativa Discloses its Docking Sites Variations

Abstract A wide variety of cellular mechanisms such as cell division and metabolic processes are maintained by protein-protein interactions (PPIs). The identification of PPI through laboratory techniques is costly, time-consuming, difficult, and challenging. However, computational techniques were generated for PPIs prediction. In alfalfa (Madicago sativa), PPI was predicted among 12 MsMAPKs and 4 MsPP2Cs using a docking approach. For homology modelling, the Swiss model was employed while PROCHECK, ERRAT, and Verify3D were used to validate 3D models. The Ramachandran plots were obtained from PROCHECK which showed value more than 90% (nPP2C1, PP2C1, PP2C, and MSK-3 revealed 92.9%, 94.2%, 92.4%, and 91.1% respectively) for high-quality structures. The HawkDock server and the BIPSPI server were used to analyse protein docking and predict interaction sites, respectively. Our findings demonstrated that MsPP2C docking sites play an important role in the identification and docking of MsMAPKs. The binding free energy ranged from -0.16Kcal/mol to -49.15Kcal/mol for all MsMAPKs and MsPP2Cs, indicating that they interact. Docking site analysis showed that there were 48 pairs of PPIs which indicated that MsPP2Cs can perform a vital role in other signaling pathways. This study found that all MsPP2Cs have docking sites for MsMAPKs, indicating that this method can accurately determine protein-protein interactions.

Chloroplast-targeted expression of recombinant crystal-protein gene in cotton: an unconventional combat with resistant pests.

Plants transformed with single Bt gene are liable to develop insect resistance and this has already been reported in a number of studies carried out around the world where Bt cotton was cultivated on commercial scale. Later, it was envisaged to transform plants with more than one Bt genes in order to combat with resistant larvae. This approach seems valid as various Bt genes possess different binding domains which could delay the likely hazards of insect resistance against a particular Bt toxin. But it is difficult under field conditions to develop homozygous plants expressing all Bt genes equally after many generations without undergoing recombination effects. A number of researches claiming to transform plants from three to seven transgenes in a single plant were reported during the last decade but none has yet applied for patent of homozygous transgenic lines. A better strategy might be to use hybrid-Bt gene(s) modified for improved lectin-binding domains to boost Bt receptor sites in insect midgut. These recombinant-Bt gene(s) would express different lectin domains in a single polypeptide and it is relatively easy to develop homozygous transgenic lines under field conditions. Enhanced chloroplast-localized expression of hybrid-Bt gene would leave no room for insects to develop resistance. We devised and successfully applied this strategy in cotton (Gossypium hirsutum) and data up to T3 generation showed that our transgenic cotton plants were displaying enhanced chloroplast-targeted Cry1Ac-RB expression. Laboratory and field bioassays gave promising results against American bollworm (Heliothis armigera), pink bollworm (Pictinophora scutigera) and fall armyworm (Spodoptera frugiperda) that otherwise, were reported to have evolved resistance against Cry1Ac toxin. Elevated levels of hybrid-Bt toxin were confirmed by ELISA of chloroplast-enriched protein samples extracted from leaves of transgenic cotton lines. While, localization of recombinant Cry1Ac-RB protein in chloroplast was established through confocal laser scanning microscopy.