First principle study of X2GaAgCl6 (X = Cs, Rb) double perovskites: structural, mechanical, vibrational, electronic, optical, SLME, thermoelectric, and thermodynamic properties for solar cell applications.

The structural, mechanical, vibrational, electronic, optical, SLME, thermoelectric, and thermodynamic properties of X2GaAgCl6 (X = Cs, Rb), a double perovskite material, were computed by employing Density Functional Theory (DFT). CASTEP and Quantum ESPRESSO were used to perform first-principles calculations. X2GaAgCl6 possesses a cubic structure with the space-group symmetry Fm-3 m. The lattice parameters of Cs2GaAgCl6 and Rb2GaAgCl6 were optimized using the energy-volume curves, resulting in values of 7.357 Å and 7.365 Å, respectively. The population analysis confirmed the charge transfer among transition metals and halogen atoms. The stability of crystal X2GaAgCl6 (X = Cs, Rb) is effectively demonstrated by analyzing phonon dispersion curves with no negative frequencies. The band structure calculations indicated the semiconducting nature of compounds with energy gaps of 0.96 eV and 0.88 eV for Cs2GaAgCl6 and Rb2GaAgCl6, respectively. The optical characteristics results confirm that the examined materials are suitable for devices working, primarily in the electromagnetic spectrum's visible region. SLME results showed that Cs2GaAgCl6 has 30% and Rb2GaAgCl6 has 27% efficiency, respectively, suggesting their use in photovoltaics. The thermoelectric properties of X2GaAgCl6 (X = Cs, Rb) were calculated by using the BoltzTraP code in the temperature range of 300 to 800 K. The quasi-harmonic Debye model was applied to calculate the thermodynamic characteristics.

GC-MS-based profiling and ameliorative potential of Carissa opaca Stapf ex Haines fruit against cardiac and testicular toxicity: An In vivo study.

Fruit of Carissa opaca Stapf ex Haines (C. opaca) is a feed additive and is commonly used against cardiac dysfunction, fever, asthma, diarrhea, gastrointestinal ailments, and skin diseases. In this study, we aimed to evaluate the metabolic profile and antioxidant potential of C. opaca fruit against carbon tetrachloride (CCl4)-induced cardiotoxicity and testicular toxicity in rats. Gas Chromatoghraphy-Mass Spectrometry (GC-MS) analysis of C. opaca fruit for the identification of potential metabolic profile, followed by methanolic extract of C. opaca and its derived fractions including n-hexane, ethyl acetate, chloroform, butanol, and aqueous were used to assess the antioxidant potential of fruits. Ten groups of rats received different treatments and got evaluated for cardiac and testicular antioxidant enzymes, histological architecture, and serum hormonal levels. GC-MS analysis of methanolic extract of C. opaca fruit showed the presence of some bioactive metabolites like cyclodecane, diethyl 2,6-pyridine dicarboxylate, tetrahydro-geraniol, S-[2-[N, N-Dimethylamino]ethyl]morpoline, 2,3-Methylenedioxyphenol, alpha-d-Glucopyranoside, 5,10-Diethoxy-2,3,7,8-tetrahydro-1H, 6H-dipyrrolo [1,2-a; 1',2'-d] pyrazine and 1,3-Benzothiazol-2(3H)-one,3-(3,3-dimethyl-1-oxobutyl) that corresponds the medicinal properties of C. opaca fruit. Prepared fractions of C. opaca fruits mitigated the toxicity induced by CCl4 in the heart and testicular tissues of rats. Oxidative stress was caused by the inhibition of activities of glutathione and other antioxidant enzymes of the body, while on the other hand elevating the levels of nitrite and hydrogen peroxide. Treatment with C. opaca fruit extract normalized the levels of enzymes, reproductive hormones, and free radicals thus restoring the histopathological and enzymatic biomarkers towards the normal group. The study supports the indigenous use of fruits as an alternative medicine against cardiac dysfunction by providing scientific evidence of protection against CCl4-induced injuries, and it also concludes the antioxidant defensive role in testicular tissues.

Pleurospermum candollei Methanolic Extract Ameliorates CCl4-Induced Liver Injury by Modulating Oxidative Stress, Inflammatory, and Apoptotic Markers in Rats.

The main objective of this study was to investigate the hepatoprotective potency of the Pleurospermum candollei methanol extract against CCl4-induced liver damage in rats. HPLC technique was used to estimate the presence of polyphenols in the methanol extract of P. candollei (PCM), while proximate analysis revealed the presence of carbohydrates, lipids, and moisture in the extract. The antioxidant potential of PCM was evaluated by 2,2-diphenylpicrylhydrazyl (DPPH) and reducing power assay, which showed a high percentage of inhibition against free radicals. Hepatotoxicity was induced by carbon tetrachloride (CCl4). CCl4 administration reduced the activity of endogenous antioxidants, whereas it increased the production of nitrites and hydrogen peroxide (H2O2) in rats. Furthermore, the level of hepatic markers in serum was also elevated after CCl4 administration. Moreover, the expression of stress-related markers, proinflammatory mediators, and apoptotic genes was enhanced in CCl4-treated rats. Coadministration of PCM along with CCl4 in rats reduced the levels of free radicals and the above genes to normal levels. CCl4 administration caused histopathological alterations in liver tissues, while cotreatment with PCM mitigated liver injuries. These findings suggest that the methanol extract of P. candollei possesses antioxidant and anti-inflammatory properties and can prevent liver injury. Further pharmacological research will be helpful in determining the effectiveness of P. candollei in humans. Development of FDA-approved plant-based anti-inflammatory drugs can help treat patients and reduce the chances of toxicity.

Jasminum humile (Linn) ameliorates CCl4-induced oxidative stress by regulating ER stress, inflammatory, and fibrosis markers in rats.

Jasminum humile (Linn) is highly valued for its medicinal properties. The pulp and decoction made from its leaves are effective for skin diseases. Juice prepared from roots is used against ringworm illness. Our current study aims to illustrate the non-toxicity and protective potential of methanol extract of Jasminum humile (JHM) against CCl4-induced oxidative stress in the liver of rats. Qualitative phytochemical screening, total flavonoids (TFC), and total phenolic content (TPC) assays were performed with JHM. The toxicity of the plant was estimated by treating female rats at different JHM doses while to assess anti-inflammatory potential of plant nine groups of male rats (six rats/group) received different treatments such as: CCl4 only (1 ml/kg mixed with olive oil in a ratio of 3:7), silymarin (200 mg/kg) + CCl4, different doses of JHM alone at a ratio of 1:2:4, and JHM (at a ratio of 1:2:4) + CCl4, and were examined for different antioxidant enzymes, serum markers, and histological changes, while mRNA expression of stress, inflammatory and fibrosis markers were assessed by real-time polymerase chain reaction analysis. Different phytochemicals were found in JHM. A high amount of total phenolic and flavonoid content was found (89.71 ± 2.79 mg RE/g and 124.77 ± 2.41 mg GAE/g) in the methanolic extract of the plant. Non-toxicity of JHM was revealed even at higher doses of JHM. Normal levels of serum markers in blood serum and antioxidant enzymes in tissue homogenates were found after co-administration of JHM along with CCl4. However, CCl4 treatment caused oxidative stress in the liver by enhancing the levels of stress and inflammatory markers and reducing antioxidant enzyme levels, while JHM treatment showed significant (P < 0.05) downregulation was in mRNA expression of those markers. Investigation of mechanism of specific signaling pathways related to apoptosis and clinical trials to assess safety and efficacy of optimal dosage of Jasminum humile will be helpful to develop FDA-approved drug.

Linum corymbulosum Protects Rats against CCl4-Induced Hepatic Injuries through Modulation of an Unfolded Protein Response Pathway and Pro-Inflammatory Intermediates.

Liver fibrosis is a major pathological feature of chronic liver disease and effective therapies are limited at present. The present study focuses on the hepatoprotective potential of L. corymbulosum against carbon tetrachloride (CCl4)-induced liver damage in rats. Analysis of Linum corymbulosum methanol extract (LCM) using high-performance liquid chromatography (HPLC) revealed the presence of rutin, apigenin, catechin, caffeic acid and myricetin. CCl4 administration lowered (p < 0.01) the activities of antioxidant enzymes and reduced glutathione (GSH) content as well as soluble proteins, whereas the concentration of H2O2, nitrite and thiobarbituric acid reactive substances was higher in hepatic samples. In serum, the level of hepatic markers and total bilirubin was elevated followed by CCl4 administration. The expression of glucose-regulated protein (GRP78), x-box binding protein-1 total (XBP-1 t), x-box binding protein-1 spliced (XBP-1 s), x-box binding protein-1 unspliced (XBP-1 u) and glutamate-cysteine ligase catalytic subunit (GCLC) was enhanced in CCl4-administered rats. Similarly, the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemo attractant protein-1 (MCP-1) was strongly increased with CCl4 administration to rats. Co-administration of LCM along with CCl4 to rats lowered (p < 0.05) the expression of the above genes. Histopathology of the liver showed hepatocyte injury, leukocyte infiltration and damaged central lobules in CCl4-treated rats. However, LCM administration to CCl4-intoxicated rats restored the altered parameters towards the levels of control rats. These outcomes indicate the existence of antioxidant and anti-inflammatory constituents in the methanol extract of L. corymbulosum.

Evaluation of Phytochemistry and Pharmacological Properties of Alnus nitida.

In the current study, the anti-inflammatory and analgesic potential of Alnus nitida (leaves and fruits) was evaluated in the Sprague-Dawley rat. Traditionally, A. nitida was used for the treatment of inflammatory ailments. However, A. nitida leaves and fruits have not been yet reported regarding any potential medicinal effects. Leaves/fruits of A. nitida were extracted with methanol and fractionated to attain n-hexane, chloroform, ethyl acetate and aqueous fractions. These extracts were then evaluated for in vivo analgesic and anti-inflammatory potential. For in vivo anti-inflammatory activity, carrageenan-induced paw edema assay, Freunds' complete adjuvant-induced edema, xylene-induced ear edema and histamine-induced paw edema models were used in rats, which showed significant (p < 0.01) reduction (70−80%) in edema in comparison of inflammatory controls. On other hand, for the analgesic assessment, hot plate assay and acetic acid-induced writhing tests were used, which showed a significant (p < 0.01) rise in latency time (40−60%) as compared with pain-induced controls. These results were comparable with standard drugs in a concentration-dependent manner and no mortality or toxicity was observed during all experiments. Then, for the identification of chemical constituents gas chromatography−mass spectrometry (GC-MS) analysis was performed, which indicated the presence of neophytadiene, 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, phytol and vitamin E, justifying the use of A. nitida to treat inflammatory disorders.

An Extensive Pharmacological Evaluation of New Anti-Cancer Triterpenoid (Nummularic Acid) from Ipomoea batatas through In Vitro, In Silico, and In Vivo Studies.

Prostate cancer (PCa) is the most common cancer in men, accounting for approximately 10% of all new cases in the United States. Plant-derived bioactive compounds, such as pentacyclic triterpenoids (PTs), have the ability to inhibit PCa cell proliferation. We isolated and characterized nummularic acid (NA), a potent PT, as a major chemical constituent of Ipomoea batatas, a medicinal food plant used in ethnomedicine for centuries. In the current study, in vitro antiproliferative potential against PCa cells (DU145 and PC3) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay; Western blot protein expression analysis; absorption, distribution, metabolism, excretion (ADME); pharmacokinetic prediction studies; and bisphenol A (BPA)-induced prostate inhibition in Sprague Dawley rats were conducted to gauge the anti-cancer ability of NA. Significant (p < 0.05 and p < 0.01) time- and dose-dependent reductions in proliferation of PCa cells, reduced migration, invasion, and increased apoptotic cell population were recorded after NA treatment (3−50 µM). After 72 h of treatment, NA displayed significant IC50 of 21.18 ± 3.43 µM against DU145 and 24.21 ± 3.38 µM against PC3 cells in comparison to the controls cabazitaxel (9.56 ± 1.45 µM and 12.78 ± 2.67 µM) and doxorubicin (10.98 ± 2.71 µM and 15.97 ± 2.77 µM). Further deep mechanistic studies reveal that NA treatment considerably increased the cleavage of caspases and downstream PARP, upregulated BAX and P53, and downregulated BCL-2 and NF-κB, inducing apoptosis in PCa cells. Pharmacokinetic and ADME characterization indicate that NA has a favorable physicochemical nature, with high gastrointestinal absorption, low blood−brain barrier permeability, no hepatotoxicity, and cytochrome inhibition. BPA-induced perturbations of prostate glands in Sprague Dawley rats show a potential increase (0.478 ± 0.28 g) in prostate weight compared to the control (0.385 ± 0.13 g). Multi-dose treatment with NA (10 mg/kg) significantly reduced the prostate size (0.409 ± 0.21 g) in comparison to the control. NA-treated groups exhibited substantial restoration of hematological and histological parameters, reinstatement of serum hormones, and suppression of inflammatory markers. This multifaceted analysis suggests that NA, as a novel small molecule with a strong pharmacokinetic and pharmacological profile, has the potential to induce apoptosis and death in PCa cells.

Chemical characterization and evaluation of the nephroprotective potential of Parrotiopsis jacquemontiana (Decne) Rehder and Periploca hydaspidis Falc crude extract in CCl4-induced Male Sprague-Dawley Rats.

Biochemical, antioxidant, serum, and urine profiles together with physical examination can deliver important information regarding animal health status, and are vital in the diagnosis and treatment of patients. CCl4, a potent nephrotoxin, was used for causing toxicity in rat kidneys. The present study aimed at exploring the nephroprotective potential of P. jacquemontiana leaves methanol extract (PJM) and P. hydaspidis whole-plant methanol extract (PHM) on kidney cells of male rats after oxidative stress and DNA damage was instigated by CCl4. Various parameters including enzymatic levels, serum profiles, urine profiles, genotoxicity, and histological studies were conducted. In renal samples of rats treated with CCl4, the antioxidant enzymes (POD, SOD, CAT), PH level, protein level, and glutathione contents were significantly (p < 0.05) declined whereas renal biochemicals (H2O2, TBARS, and nitrite), specific gravity, level of urea, urobilinogen, serum BUN and creatinine were markedly (p < 0.05) increased relative to control group. Co-administration of PJM and PHM with CCl4 displayed protective ability against CCl4 intoxication by restoring activities of antioxidant enzymes, urine profile, biochemical parameters, and serum profile in rats. CCl4 also induced prominent DNA damages and glomerular atrophy with abnormal appearance of glomerulus and Bowman's capsule. These damages results in impaired corticular sections, edema in Bowman's capsule, accumulation of necrotic cells, dilation of convoluted tubules, and narrowing of space between Bowman's capsule, which were successfully ameliorated after co-administration of PJM and PHM fractions in a dose-dependent manner (200 and 400 mg/kg b.w.). The results obtained suggest the therapeutic role of PJM and PHM in oxidative-stress related disorders of kidney and may be helpful in kidney trauma.

In vitro antimicrobial and cytotoxic manifestations of Dicliptera roxburghiana.

Emerging resistance in microorganisms is a growing threat to human beings due to its role in pathological manifestations in different infectious diseases. This study was designed to investigate the antimicrobial and cytotoxic potential of methanol extract of Dicliptera roxburghiana and all its derived fractions. Antibacterial (against six bacterial strains) and antifungal (against four fungal strains) activities were investigated by agar well diffusion method and agar slants method, respectively. Cytotoxicity assay was carried out by using Brine shrimps eggs. In antibacterial evaluation, MIC values and zone of inhibition were measured and were found very effective for DRME, DRHF, DRCF and DREF while these were moderate for DRBF and DRAF. For antifungal assay, DRME and DRHF were potently active and showed more than 70% fungal growth inhibition where as DRCF and DRBF were also displaying appreciable inhibition. Cytotoxic measurements were very good for DRME, DRHF and DRAF with LD50 values 215, 199 and 392µg/ml respectively. These results confirmed antimicrobial and cytotoxic potential of the plant and all its derived fractions. Hence it can be concluded that plant contain some important compounds that can be used as antimicrobial source for the treatment of different infectious disease.

Investigation of Chemopreventive and Antiproliferative Potential of Dicliptera roxburghiana.

CONTEXT: Carcinogenesis causes much human misery. It is a process involving multistage alterations. Medicinal plants are candidates for beneficial anticancer agents. OBJECTIVES: Investigation of anticancer proficiencies of the plant Dicliptera roxburghiana. MATERIAL AND METHODS: Crude extract and derived fractions were inspected for their inhibitory potential against nuclear factor KB (NFκB), nitric oxide synthase inhibition, aromatase inhibition and induction of quinone reductase 1 (QR 1). Antiproliferative activity was determined by using various cancer cell lines for example hormone responsive breast cancer cell line MCF-7, estrogen receptor negative breast cancer cell line MDA-MB-231, murine hepatoma cells Hepa 1c1c7, human neuroblastoma cells SK-N-SH and neuroblastoma cells MYCN-2. RESULTS: Ethyl acetate and n-butanol fractions of D. roxburghiana were strongly active against NFκB with IC50 of 16.6 ± 1.3 and 8.4 ± 0.7 µg/ml respectively with 100% survival. Chloroform fraction of the plant exhibited an induction ratio of 2.4 ± 0.09 with CD value of 17.7 µg/ml. Regarding the nitrite assay, the n-hexane fraction exhibited significant inhibition of NO activity with IC50 of 17.8 ± 1.25 µg/ml. The n-butanol fraction exhibited strong antiproliferative activity against IcIc-7 cell lines with IC50 values of 13.6 ± 1.91 µg/ml; against MYCN-2 a cytotoxic effect developed with dose dependence, with IC50 of 12.6 ± 1.24 µg/ml. In antiproliferative activity against SK-N-SH cell lines, chloroform, ethyl acetate and n-butanol fractions were efficiently active with IC50 values of 11.2 ± 0.84, 14.6 ± 1.71 and 16.3 ± 1.57 respectively. DISCUSSION AND CONCLUSION: It was demonstrated that various fractions of D. roxburghiana displayed appreciable anticancer characteristics and could be a potent source for the development of anticancer leads.

Green synthesized silver nanoparticles (AgNPs) from Parrotiopsis jacquemontiana (Decne) Rehder leaf extract and its biological activities.

Parrotiopsis jacquemontiana (Decne) Rehder aqueous extract of leaf was used for biosynthesis of AgNPs and characterized through UV-Visible spectroscopy, X-ray diffraction, Fourier-transform-infrared, diffraction light scattering, and scanning electron microscope analysis. Moderate to strong antioxidant activity during in vitro antioxidant assays for scavenging of 2,2-diphenyl-1-picryl hydrazyl (DPPH), hydroxyl (OH), nitric oxide (NO) radicals, iron chelation, and inhibition of ß-carotene bleaching was recorded with minimum IC50 value (27.70 ± 2.67 µg/ml) calculated for OH radicals. The AgNPs were evaluated against six multidrug resistant human bacterial strains and minimum inhibitory concentration (MIC) along with minimum bactericidal concentration (MBC) values was determined and all were found remarkably susceptible. The bacterial strain Staphylococcus aureus was the most susceptible with MIC = 5 µg/ml and MBC = 10 µg/ml. Among six fungal strains, Fumigatus esculentum was the most susceptible with MIC and MBC of 10 µg/ml. 3-(4,5-Dimethylthiazol-2 yl)-2,5-diphenyltetrazolium bromide (MTT) screening assay against cancer cell lines (HCCLM3, HEPG2, MDA-MB 231, and MCF-7) revealed the least IC50 values against HCCLM3 (74.20 ± 5.04) and MCF-7 (91.90 ± 1.17). While no cytotoxicity against normal cell lines; LO2 and MCF-10a was recorded. Parrotiopsis jacquemontiana silver nanoparticles (PJAgNPs) significantly (p > .001) prevented the migration of HCCLM3 cells in a dose-dependent style, relative to control. The wound healing potential of AgNPs in rat was found higher (p < .05) for wound contraction rates, hydroxyproline content, hemostatic and re-epithelization and regeneration efficiency in comparison to the reference group.

Indigofera linifolia ameliorated CCl4 induced endoplasmic reticulum stress in liver of rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigofera linifolia (L.f.) Retz. is used in subcontinent for liver disorders, in wounds, febrile eruption and as diuretic. AIM OF STUDY: The current study evaluates the protective effects of the methanol extract of Indigofera linifolia (ILM) on CCl4-induced endoplasmic reticulum (ER) stress in liver of rat. METHODS: ILM was analyzed for phytochemical classes, total phenolic (TPC) and flavonoid content (TFC) as well as multidimensional in vitro antioxidant assays. Male (Sprague Dawley) rats were dispersed into seven groups (6 rats/group) receiving 0.9% saline (1 ml/kg bw), CCl4 (1 ml/kg bw) diluted in olive oil (3:7 v/v), silymarin (200 mg/kg bw) + CCl4 (30% v/v), ILM (150 mg/kg bw) + CCl4 (30% v/v), ILM (300 mg/kg bw) + CCl4 and ILM alone (either 150 mg/kg bw or 300 mg/kg bw). RESULTS: ILM extract was constituted of different phytochemical classes. Co-administration of ILM along with CCl4 to rat revert the level of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and total bilirubin in blood serum and antioxidant parameters in liver. Further, CCl4 increased the level of ER stress markers and inflammatory mediators while decreased level of GCLC and Nrf-2 in liver tissues of rat. CCl4-induced histopathological variations were reduced with ILM co-administration in liver tissues. CONCLUSION: The results suggest that active phyto-constituents of I. linifolia might be responsible for its antioxidant, anti-inflammatory and gene-regulating activities.

Integrative analysis reveals methylenetetrahydrofolate dehydrogenase 1-like as an independent shared diagnostic and prognostic biomarker in five different human cancers.

BACKGROUND: Defects in methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) expression have earlier been examined in only a few human cancers. OBJECTIVES: Multi-omics profiling of MTHFD1L as a shared biomarker in distinct subtypes of human cancers. METHODS: In the current study, for the multi-omics analysis of MTHFD1L in 24 major subtypes of human cancers, a comprehensive in silico approach was adopted to mine different open access online databases including UALCAN, Kaplan-Meier (KM) plotter, LOGpc, GEPIA, Human Protein Atlas (HPA), Gene Expression across Normal and Tumor tissue (GENT2), MEXPRESS, cBioportal, STRING, DAVID, TIMER, and Comparative Toxicogenomics Database (CTD). RESULTS: We noticed that the expression of MTHFD1L was significantly higher in all the analyzed 24 subtypes of human cancers as compared with the normal controls. Moreover, MTHDF1L overexpression was also found to be significantly associated with the reduced overall survival (OS) duration of Bladder urothelial cancer (BLCA), Head and neck cancer (HNSC), Kidney renal papillary cell carcinoma (KIRP), Lung adenocarcinoma (LUAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that MTHFD1L plays a significant role in the development and progression of these cancers. We further noticed that MTHFD1L was also overexpressed in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of MTHFD1L-associated genes in five diverse pathways. We also explored few interesting correlations between MTHFD1L expression and its promoter methylation, genetic alterations, CNVs, and between CD8+ T immune cells level. CONCLUSION: In conclusion, our results elucidated that MTHFD1L can serve as a shared diagnostic and prognostic biomarker in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features.

CTHRC1 expression is a novel shared diagnostic and prognostic biomarker of survival in six different human cancer subtypes.

According to the previous reports, the collagen triple helix repeat containing 1 (CTHRC1) causes tumorigenesis by modulating the tumor microenvironment, however, the evidence is limited to a few human cancer subtypes. In the current study, we analyzed and validated the CTHRC1 expression variations in 24 different human cancer tissues paired with normal tissues using publically available databases. We observed that CTHRC1 was overexpressed in all the 24 major subtypes of human cancers and its overexpression was significantly associated with the reduced overall survival (OS) duration of head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), Lung adenocarcinoma (LUAD), stomach adenocarcinoma (STAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that CTHRC1 plays a significant role in the development and progression of these cancers. We further noticed that CTHRC1 was also overexpressed in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of CTHRC1 associated genes in seven diverse pathways. We also explored few interesting correlations between CTHRC1 expression and promoter methylation, genetic alterations, CNVs, CD8+ T immune cells infiltration, and tumor purity. In conclusion, CTHRC1 can serve as a shared diagnostic and prognostic biomarker in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features.

Multi-Omics Analysis Identified TMED2 as a Shared Potential Biomarker in Six Subtypes of Human Cancer.

INTRODUCTION: Cancer is one of the most common malignancies and the leading cause of death worldwide. As a member of the transmembrane emp24 domain (Tmed)/p24 family of proteins, TMED2 expression variations have been documented earlier in only a few subtypes of human cancers, and the multi-omics profiling of TMED2 as a shared biomarker in different other subtypes of human cancers remains to be uncovered. METHODS: In the current study, TMED2 multi-omics analysis in 24 major subtypes of human cancer was performed using different authentic online databases and bioinformatics analysis including UALCAN, Kaplan-Meier (KM) plotter, Human Protein Atlas (HPA), GENT2, MEXPRESS, cBioportal, STRING, DAVID, TIMER, and CTD. RESULTS: In general, the TMED2 expression in 24 major subtypes of human cancers was higher relative to normal controls and was also strongly associated with the lower overall survival (OS) and relapse-free survival (RFS) duration of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. This implies that TMED2 plays a significant role in the development and progression of these cancers. Furthermore, the TMED2 overexpression was also correlated with different clinicopathological features of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. TMED2-associated genes network was involved in 3 diverse pathways, and finally, few stronger correlations were also explored between TMED2 expression and its promoter methylation level, genetic alterations, and CD8+ T immune cells level. CONCLUSION: In conclusion, via this in silico study, we have elucidated that TMED2 can serve as a shared diagnostic and prognostic biomarker in CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients of different clinicopathological features but, further in vitro and in vivo research should be carried out to confirm these findings.

Characterization and phytochemical constituents of Periploca hydaspidis Falc crude extract and its anticancer activities.

The current study aims to investigate the anticancer potential of Periploca hydaspidis extracts against HCCLM3 and MDA-MB 231 cell lines with invasive properties and to identify molecular targets underlying its action mechanism. Cytotoxic screening of plant extracts was done via MTT assay against liver and breast cancer cell lines and GC/MS of the best cytotoxic fraction was performed to identify its chemical composition. Flow cytometry detected apoptosis and cell-cycle changes after drug treatment. The specified cells were studied for migration and invasion potential along with performing western blot analysis of proteins involved in apoptosis, cell-cycle, metastasis, and MAPK (Mitogen-activated protein kinase) cell-signaling pathway. The results revealed the crude methanol (PHM) fraction of P. hydaspidis shown dose and time dependent cell-proliferative inhibition response. GC/MS analysis detected 54 compounds of which fatty acids (29.8%), benzenoids (15.7%), and esters (14.3%) constituted the bulk. The inhibitory effect against cancer cells was linked with cell-cycle arrest at G0/G1 phase, induction of apoptosis, reduced migration and invasion capabilities post treatment. PHM induced apoptosis via downregulation of anti-apoptotic (survivin, B-cell lymphoma Extra-large; BCL-XL, X-linked inhibitor of apoptosis protein; XIAP, Myelocytomatosis; C-myc), metastatic (Matrix metallopeptidases 9/2; MMP9/2), and cell-cycle regulatory (cyclin D1 and E) proteins, whereas upregulation of pro-apoptotic proteins (Bcl-2 homologous antagonist/killer; BAK, Bcl-2-Associate X protein; BAX, cleaved caspases; 3,7,8,9, and PARP) and activation of MAPK (Jun amino-terminal kinase; JNK and P38) pathway. P38 was needed for PHM-induced apoptosis, where the inhibition of P38 by pharmacological inhibitor (SB239063) diminished the apoptotic effects. Overall, our results conclude that PHM can inhibit cell-proliferation and induce apoptotic effects by activation of P38 MAPK cell-signaling pathway. This suggests the methanol fraction of P. hydaspidis (PHM) to have anticancer compounds, potentially useful for treating liver and breast cancer. In future, one-step advance studies of PHM regarding its role in metastatic inhibition, immune response modulation for reducing tumor, and inducing apoptosis in suitable animal models would be an interesting and promising research area.

Chemical composition and pharmacological bio-efficacy of Parrotiopsis jacquemontiana (Decne) Rehder for anticancer activity.

Consistent STAT3 (Single transducer and activator of transcription 3) activation is observed in many tumors and promotes malignant cell transformation. In the present investigation, we evaluated the anticancer effects of Parrotiopsis jacquemontiana methanol fraction (PJM) on STAT3 inhibition in HCCLM3 and MDA-MB 231 cells. PJM suppressed the activation of upstream kinases i.e. JAK-1/2 (Janus kinase-1/2), and c-Src (Proto-oncogene tyrosine-protein kinase c-Src), and upregulated the expression levels of PIAS-1/3 (Protein Inhibitor of Activated STATs-1/3), SHP-1/2 (Src-homology region 2 domain-containing phosphatase-1/2), and PTP-1ß (Protein tyrosine phosphatase 1 ß) which negatively regulate STAT3 signaling pathway. PJM also decreased the levels of protein products conferring to various oncogenes, which in turn repressed the proliferation, migration, invasion, and induced apoptosis in cancer cell lines. The growth inhibitory effects of PJM on cell-cycle and metastasis were correlated with decreased expression levels of CyclinD1, CyclinE, MMP-2 (Matrix metalloproteinases-2), and MMP-9 (Matrix metalloproteinases-9). Induction of apoptosis was indicated by the cleavage and subsequent activation of Caspases (Cysteine-dependent Aspartate-directed Proteases) i.e. caspase-3, 7, 8, 9, and PARP (Poly (ADP-ribose) polymerase) as well as through the down-regulation of anti-apoptotic proteins. These apoptotic effects of PJM were preceded by inhibition of STAT3 cell-signaling pathway. STAT3 was needed for PJM-induced apoptosis, and inhibition of STAT3 via pharmacological inhibitor (Stattic; SC-203282) abolished the apoptotic effects. Conclusively, our results demonstrate the capability of PJM to inhibit cancer cell-proliferation and induce apoptosis by suppressing STAT3 via upregulation of STAT3 inhibitors and pro-apoptotic proteins whereas the down-regulation of upstream kinases and anti-apoptotic protein expression. In future, one-step advance studies of PHM regarding its role in metastatic inhibition, immune response modulation for reducing tumor, and inducing apoptosis in suitable animal models would be an interesting and promising research area.

In vitro anticancer activity of extracted oil from Parrotiopsis jacquemontiana (Decne) Rehder.

BACKGROUND: Parrotiopsis jacquemontiana, commonly referred to as "Beranj" in the local community, is widely used traditionally and has numerous health benefits. However, no studies have been conducted to investigate its anticancer potential, particularly its extracted oil. PURPOSE: The present study was put forth to appraise the anticancer potential of Parrotiopsis jacquemontiana extracted oil against liver (hcclm3 and hepg2) and breast cancer (mda-mb 231 and mcf-7) cell lines relative to normal cell lines (lo2 and mcf-10a) via MTT assay. METHODS: Flow cytometry indicated the apoptotic effect whereas invasion and migration capabilities of oil against cancer cells were determined by Matrigel invasion chamber and wound-scratch assays. RESULTS: The results of oil revealed a time and dose-dependent increase in cell proliferation inhibition, conferring to least IC50 shown against hcclm3 (144.9 ± 0.75 µg/ml) and mda-mb 231 (145.7 ± 0.32 µg/ml) cell line at 72 h, whereas no cytotoxic effect on normal cells was observed. In addition, the oil significantly (p < 0.001) suppressed the migration and invasion of hcclm3 and mda-mb 231 cells, showing noteworthy anti-metastatic potential. Furthermore, cell death was confirmed by Annexin‒V/PI staining where the maximum apoptotic percentage was calculated for oil (200 µg/ml) alongside mda-mb 231 conferring to 15.36 ± 1.22, 26.7 ± 1.2, and 36.43 ± 1.65 at 24, 48, and 72 h whereas 12.33 ± 1.05, 19.36 ± 1.62, and 29.3 ± 0.79 was recorded alongside hcclm3 at similar time intervals, respectively. CONCLUSION: In conclusion, the extracted oil exhibited strong anti-proliferative, anti-metastatic, and apoptotic effects and therefore may have potential applications in cancer treatment, however, further studies of oil regarding the action mechanisms and compounds involved in anticancer therapy are necessary.

Seroprevalence and Associated Risk Factors of Bovine Brucellosis in District Gujranwala, Punjab, Pakistan.

Bovine brucellosis is a contagious zoonotic disease that causes economic losses through abortion and infertility. A cross-sectional study was designed to determine the seroprevalence and associated risk factors of bovine brucellosis in district Gujranwala of Punjab, Pakistan. A total of 220 bovine sera (112 from buffaloes, 108 from cattle) from 46 unvaccinated herds were collected. Parallel testing by the Rose Bengal Plate Test (RBPT) and Indirect Enzyme-linked Immunosorbent Assay (I-ELISA) showed a 58.7% (27/46) herd-level and 22.7% (50/220) animal-level seroprevalence. Seroprevalence was higher (p < 0.001, OR = 7.62) in adult animals (37.2%) compared to younger animals (4.9%). A herd size of >10 animals (p = 0.021, OR = 7.83), less housing space (p = 0.037, OR = 6.39) and history of abortion at the farm (p = 0.023, OR = 5.6) were found as risk factors associated with the seropositivity of brucellosis. There was a substantial agreement between the RBPT and I-ELISA results (Cohen's kappa coefficient (κ) = 64.16, percent agreement = 89.5%). In conclusion, a relatively higher seroprevalence was found compared to the previous reports from the country. Standardization and validation of the advanced diagnostic tests would be needed. Biosecurity, personal protection, quarantine measures and routine screening of animals at the farm level and disease awareness programs and consumption of pasteurized milk in the human population will be helpful in preventing the transmission/zoonosis of the disease.

Green synthesized AgNPs from Periploca hydaspidis Falc. and its biological activities.

Characterization of bio-synthesized silver nanoparticles (AgNPs) using Periploca hydaspidis (PHAgNPs) whole plant extract for the first time via UV-Visible spectroscopy, XRD, FTIR, DLS, and SEM analysis techniques was done. A rich variety of phytochemicals in P. hydaspidis aqueous extract (PHA) functioned as possible reducing and capping agents for AgNPs synthesis. In vitro antioxidant activities (DPPH, Iron chelating, Hydroxyl ion, Nitric oxide, and ß-carotene bleaching assays) of PHAgNPs revealed least IC50 values especially in hydroxyl ion (39.08 ± 0.88 µg/mL) and nitric oxide (37.53 ± 2.24 µg/mL) scavenging assays relative to standard controls (ascorbic acid, rutin, and gallic acid) and PHA. In addition, visible inhibition zone diameters were formed around discs against all pathogenic microbial strains including multi-drug resistant strains (MDR's). MIC and MBC/MFC were depicted least in PHAgNPs with maximum bactericidal/fungicidal effects. MTT assay displayed a significant antiproliferative potential of PHAgNPs against HCCLM3, MCF-7, MDA-MB 231, and HEPG2 cancer cell lines, where least IC50 values were recorded against HEPG2 (12.97 ± 0.04 µg/mL) and MCF-7 (5.73 ± 0.22 µg/mL). Furthermore, PHAgNPs considerably (p > 0.001) prevented the migration of MCF-7 cancer cells in vitro whereas in in vivo wound healing assay, faster skin regeneration, and epithelization in wound biopsies was observed via histological analysis. PHAgNPs treated group rats significantly increased (p < 0.05) the wound contraction rate, hydroxyproline content and hemostatic potential compared to control and PHA-treated groups.