Development and In Vitro characterization of Azadirachta Indica Gum grafted polyacrylamide Based pH-Sensitive Hydrogels to improve the Bioavailability of Lansoprazole.

The present study intended to develop a pH-responsive hydrogel based on Neem gum (Ng) to improve Lansoprazole (LSP) oral bioavailability. pH-responsive hydrogel formulations (F1-F9) were prepared using different Ng ratios, Acrylamide (AAm), and methylene-bis-acrylamide (MBA). The formulated hydrogels were characterized through FTIR, thermal analysis, swelling ratio, SEM, sol-gel ratios, In-Vitro drug release, and cytotoxicity analysis. Azadirachta Indica was extracted to produce a powder containing 21.5 % Ng. Prepared hydrogels showed maximum swelling at pH 7.4, whereas the swelling at an acidic pH was insignificant. LSP-loaded hydrogel demonstrated a regulated release of LSP for up to 24 h and indicated a Super Case II transport release mechanism. During the cytotoxic evaluation, the delivery system showed minimal cytotoxicity towards normal cells, while percent cytotoxicity was carried out for a longer duration (up to 96 h). The present study revealed Azadirachta indica gum-based pH-responsive hydrogel as a promising technique for precisely delivering LSP.

Predominance of blaNDM- and blaIMP-Harboring Escherichia coli Belonging to Clonal Complexes 131 and 23 in a Major University Hospital.

Background and Objectives: Carbapenem resistance is a growing global challenge for healthcare, and, therefore, monitoring its prevalence and patterns is crucial for implementing targeted interventions to mitigate its impact on patient outcomes and public health. This study aimed to determine the prevalence of carbapenem resistance among Escherichia coli (E. coli) strains in the largest tertiary care hospital of the capital territory of Pakistan and to characterize the isolates for the presence of antimicrobial resistance genes. Additionally, the most prevalent sequence types were analyzed. Materials and Methods: A total of 15,467 clinical samples were collected from November 2020 to May 2022, underwent antimicrobial susceptibility testing, and were analyzed for antimicrobial resistance genes through conventional PCR and sequence typing using MLST. Results: In carbapenem-resistant E. coli (CR-EC), 74.19% of isolates harbored the blaNDM gene, with blaNDM-1 (66.96%), blaNDM-5 (12.17%), and blaNDM-7 (20.87%) variants detected. Additionally, blaIMP was found in 25.81% and blaOXA-48 in 35.48% of isolates. The presence of blaCTX-M15 and blaTEM was identified in 83.87% and 73.55% of CR-EC isolates, respectively, while armA and rmtB were detected in 40% and 65.16% of isolates, respectively. Colistin and tigecycline were the most effective drugs against CR-EC isolates, with both showing an MIC50 of 0.5 µg/mL. The MIC90 for colistin was 1 µg/mL, while for tigecycline, it was 2 µg/mL. MLST analysis revealed that the CR-EC isolates belonged to ST131 (24.52%), ST2279 (23.87%), ST3499 (16.13%), ST8051 (15.48%), ST8900 (9.68%), ST3329 (7.10%), ST88 (1.94%), and ST6293 (1.29%). The ST131 complex (70.97%) was the most prevalent, harboring 95.65% of the blaNDM gene, while the ST23 complex (18.06%) harbored 62.50% of the blaIMP gene. Conclusions: Implementing large-scale surveillance studies to monitor the spread of specific pathogens, along with active infection control policies, is crucial for the effective containment and prevention of future epidemics.

Molecular Mechanisms and Pathophysiological Significance of Eryptosis.

Despite lacking the central apoptotic machinery, senescent or damaged RBCs can undergo an unusual apoptosis-like cell death, termed eryptosis. This premature death can be caused by, or a symptom of, a wide range of diseases. However, various adverse conditions, xenobiotics, and endogenous mediators have also been recognized as triggers and inhibitors of eryptosis. Eukaryotic RBCs are unique among their cell membrane distribution of phospholipids. The change in the RBC membrane composition of the outer leaflet occurs in a variety of diseases, including sickle cell disease, renal diseases, leukemia, Parkinson's disease, and diabetes. Eryptotic erythrocytes exhibit various morphological alterations such as shrinkage, swelling, and increased granulation. Biochemical changes include cytosolic Ca2+ increase, oxidative stress, stimulation of caspases, metabolic exhaustion, and ceramide accumulation. Eryptosis is an effective mechanism for the elimination of dysfunctional erythrocytes due to senescence, infection, or injury to prevent hemolysis. Nevertheless, excessive eryptosis is associated with multiple pathologies, most notably anemia, abnormal microcirculation, and prothrombotic risk; all of which contribute to the pathogenesis of several diseases. In this review, we provide an overview of the molecular mechanisms, physiological and pathophysiological relevance of eryptosis, as well as the potential role of natural and synthetic compounds in modulating RBC survival and death.

Combined Supplementation of Clostridium butyricum and Bifidobacterium infantis Diminishes Chronic Unpredictable Mild Stress-Induced Intestinal Alterations via Activation of Nrf-2 Signaling Pathway in Rats.

Exposure to long-term chronic unpredictable mild stress (CUMS) can cause redox imbalance and inflammation, which may affect the integrity of the gut barrier. The present study was conducted to investigate the effects of a probiotics bacterium mixture, including Clostridium butyricum (C. butyricum) and Bifidobacterium infantis (B. infantis), on the intestinal homeostasis in rats exposed to multiple low-intensity stressors for 28 days. The mechanism of CUMS-induced altered intestinal homeostasis was evaluated by focusing on the nuclear factor-E2-related factor-2 (Nrf-2) pathway. In contrast to the CUMS group, probiotic mixture supplementation significantly (p < 0.01) reversed the stress-induced elevated corticosterone level, protein and lipid oxidation, and increased enzymatic and non-enzymatic antioxidant levels, as well as upregulated Nrf-2/HO-1 pathway. Probiotics supplementation further significantly (p < 0.01) decreased the CUMS-induced inflammation, altered T-lymphocyte levels, and suppressed the protein expression of nuclear factor kappa B (NF-κB) in rat intestines. Improvement in histological changes and intestinal barrier integrity further validate the beneficial effects of probiotic mixtures on CUMS-induced altered intestinal morphology. In conclusion, our results suggest that the combination of C. butyricum and B. infantis significantly attenuated CUMS-induced oxidative stress, inflammation, and T-lymphocyte modulation by upregulating Nrf-2/HO-1 signaling and inhibiting NF-κB expression in rat intestine.

Analysis of Biochemical and Antimicrobial Properties of Bioactive Molecules of Argemone mexicana.

This study identified phytochemicals in Argemone mexicana (A. mexicana) extracts that are responsible for its medicinal properties, and the best solvent for their extraction. The extracts of the stem, leaves, flowers, and fruits of A. mexicana were prepared at low (corresponding to room temperature) and high temperatures (corresponding to the boiling points) in various solvents, viz., hexane, ethyl acetate, methanol, and H2O. The UV-visible absorption spectra of various phytoconstituents in the isolated extracts were determined through spectrophotometry. Qualitative tests for the screening of phytoconstituents in the extracts were performed to identify various phytochemicals. We identified the presence of terpenoids, alkaloids, cardiac glycosides, and carbohydrates in the plant extracts. The antioxidant and anti-human immunodeficiency virus type 1 reverse transcriptase (anti-HIV-1RT) potential, as well as the antibacterial activity of various A. mexicana extracts were determined. These extracts showed strong antioxidant activities. The extracts exhibited antimicrobial activities against Salmonella typhi, Staphylococcus epidermis, Citrobacter, Neisseria gonorrhoeae, and Shigella flexineri. These extracts significantly inhibited HIV-1 reverse transcriptase activity. The aqueous leaf extract prepared at a temperature equivalent to the boiling point, i.e., 100 °C, was identified to be the most active against pathogenic bacteria and HIV-1 RT.

Epigallocatechin gallate and coenzyme Q10 attenuate cisplatin-induced hepatotoxicity in rats via targeting mitochondrial stress and apoptosis.

Despite the extensive use of cisplatin (CP) as a chemotherapeutic agent, its clinical use is often restricted by undesirable side effects, such as toxicity to normal tissues. The aim of this study was to probe the effect of a combinatorial treatment of low multiple doses of antioxidants on CP-induced toxicity and the mitochondrial apoptotic pathway in hepatocytes. Animals received a single toxic dose of CP (7.5 mg/kg body weight) with or without combined multiple doses of epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) (15 and 5 mg/kg body weight, respectively). CP-treated animals showed altered biochemical parameters, denoting hepatotoxicity, which was markedly improved by the multidose treatment with EGCG + CoQ10. The increased levels of oxidants found in the cytosolic and mitochondrial fractions isolated from the liver of CP-administered rats were significantly attenuated by the combinatorial doses of antioxidants. EGCG + CoQ10 ameliorated the CP-induced compromised antioxidant defenses, oxidative modification of macromolecules, decreased activities of respiratory chain enzymes, altered membrane depolarization, and swelling of liver mitochondria. Furthermore, EGCG + CoQ10 treatment inhibited CP-induced apoptosis by suppressing the activation and mitochondrial accumulation of proapoptotic proteins and preventing the inhibition of antiapoptotic protein expression, cytochrome c efflux, caspase-3 activation, and DNA fragmentation. Histological findings further confirmed the protective effects of EGCG + CoQ10 against CP-induced cellular injury. Our findings revealed that the combination of EGCG and CoQ10, owing to their individual antioxidant properties, can be an effective remedy, which by maintaining redox hemostasis attenuate the mitochondrial stress-mediated molecular and cellular processes involved in CP-induced liver toxicity and cell death.

Effect of pre- and post-combined multidoses of epigallocatechin gallate and coenzyme Q10 on cisplatin-induced oxidative stress in rat kidney.

The nephroprotective effect of coenzyme Q10 and epigallocatechin gallate was investigated in rats with acute renal injury induced by a single nephrotoxic dose of cisplatin. Two days prior to cisplatin administration, epigallocatechin gallate and coenzyme Q10 alone and in four different combinations were given for 6 days. The treatment with antioxidants significantly protected the cisplatin-induced increase in the levels of blood urea nitrogen and serum creatinine. Both the antioxidants alone or in different combinations significantly compensated the increased malondialdehyde and reduced glutathione levels. Moreover, the decrease in the activities of superoxide dismutase, catalase, and glutathione peroxidase and the concentration of selenium, zinc, and copper ions were significantly attenuated in renal tissue. In conclusion, epigallocatechin gallate and coenzyme Q10 are equally effective against cisplatin-induced nephrotoxicity, whereas the intervention by combining these two antioxidants was found to be highly effective at low doses in attenuating oxidative stress in rat kidney.

Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.

Poly(ADP-ribose) polymerase-1 (PARP-1) functions as a DNA damage sensor and signaling molecule. It plays a vital role in the repair of DNA strand breaks induced by radiation and chemotherapeutic drugs; inhibitors of this enzyme have the potential to improve cancer chemotherapy or radiotherapy. Three-dimensional quantitative structure activity relationship (3D QSAR) models were developed using comparative molecular field analysis, comparative molecular similarity indices analysis and docking studies. A set of 88 molecules were docked into the active site of six X-ray crystal structures of poly(ADP-ribose)polymerase-1 (PARP-1), by a procedure called multiple receptor conformation docking (MRCD), in order to improve the 3D QSAR models through the analysis of binding conformations. The docked poses were clustered to obtain the best receptor binding conformation. These dock poses from clustering were used for 3D QSAR analysis. Based on MRCD and QSAR information, some key features have been identified that explain the observed variance in the activity. Two receptor-based QSAR models were generated; these models showed good internal and external statistical reliability that is evident from the [Formula: see text], [Formula: see text] and [Formula: see text]. The identified key features enabled us to design new PARP-1 inhibitors.

Phytochemical profiling, antioxidant potential and cytotoxic activity of Sargassum prismaticum extracts: implications for therapeutic applications.

Seaweeds are sources of bioactive compounds with medicinal properties, which make them attractive candidates for natural therapeutic agents. Marine brown algae are known to possess anti-inflammatory, hepatoprotective, anticancer properties, etc. Present study was carried out to identify the phytochemical constituents, antioxidant and cytotoxic activities of Sargassum prismaticum in two different solvents viz., chloroform and methanol. Chloroform was found to be the superior solvent for phenol and flavonoid extraction. Antioxidant activity was determined using DPPH and ABTS assays; however, the methanolic extract demonstrated better antioxidant potential. The highest cell cytotoxicity with an IC50 value of 7.6 ± 0.02 µg/mL was observed in methanolic extract, while the chloroform extract had an IC50 value of 9.6 ± 0.03 µg/mL against U937 cell line. These finding suggest that Sargassum prismaticum possesses potent antioxidant and cytotoxic properties, making it a potential candidate for further study as a novel antioxidant drug source.

Flexible high electrochemical collagen/lignin composite hydrogel for sensing and supercapacitor applications.

Synthesis of polymer-based highly conductive hydrogels from natural and renewable sources with robust mechanical performances in flexible electronics remains a great challenge. In this research, a dynamic redox system is designed by using collagen (CL), sulfonate lignin (SL), acrylic acid (AA), and Al3+ to synthesize CL/PAA/SL/Al hydrogels. The formation of effective complexes of Al3+ with the abundant functional groups of CL, SL and PAA, the prepared hydrogel delivers various specific properties, for example, excellent ionic conductivity (4.61 S·m-1), stretchability and antimicrobial performance. The CL/PAA/SL/Al hydrogel demonstrates good mechanical strength, while the maximum tensile strength of the hydrogels is ∼604 kPa at a stretching of 1254 %, and the maximum compressive strength is ∼0.45 MPa, with the maximum stretching of 59.6 %. The CL/PAA/SL/Al hydrogel acts as a flexible strain sensor with high sensitivity. Enough hydroxyl and carboxyl groups in the hydrogels are essential for delivering the maximum 191 mV of open circuit voltage (Voc) rendered during moisture spraying. The supercapacitor assembled from CL/PAA/SL/Al hydrogel manifests specific capacitance (Cs), maximum energy density (Ed) and power density (Pd) of 268.75 F·g-1, 23.89 Wh·kg-1 and 2.4 kW·kg-1, respectively. The supercapacitor can retain its capacitance of 95.8 % after 5000 consecutive charge-discharge cycles.

Effect of chronic unpredictable stress on short term dietary restriction and its modulation by multivitamin-mineral supplementation.

Dietary restriction (DR) lowers steady-state levels of oxidative stress and alters behavioral, physiological and biochemical responses in mammals. However, various factors effect its application in humans like socio-cultural, appetite and the daily life stress. Physiological and psychological stress owing to fast-paced lifestyles, translates into oxidative stress. In this work, the role of chronic unpredictable stress (CUS) on the effects of short term DR in mice in terms of biochemical and oxidative stress parameters was investigated. Further, the modulatory role of multivitamin-mineral supplement (MVM) on CUS and DR induced biochemical changes was studied to delineate the role of micronutrient supplementation. DR treatment increased the antioxidant status in the circulation and liver of mice but in the presence of chronic stressors there was a significant shift towards the pro-oxidant state. A decrease was found in the activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione-S-transferase and glutathione reductase in the rats exposed to CUS with DR (CUS+DR), with an increased malondialdehyde and a decreased glutathione (GSH) levels as compared to the controls. Liver function enzymes-glutamate oxaloacetate transaminase and glutamate pyruvate transaminase were increased and a significant DNA damage was observed. Oral MVM supplement significantly improved this oxidative deterioration. Hence, MVM supplementation appears to potentially offer an effective intervention in the DR regimen to combat daily life physical and mental stress.

Cancer-Preventive Activity of Argemone mexicana Linn Leaves and Its Effect on TNF-α and NF-κB Signalling.

Skin cancer is the 5th most common cancer in Western countries with a surge in case occurrences making it a global burden on healthcare systems. The present study aims to evaluate the cancer-preventive activity of an ethanolic extract of Argemone mexicana Linn leaves (AML). The DMBA/TPA method was used to induce skin cancer in mice. Experimental animals were divided into three pretreatment groups of 100 mg/kg BW, 250 mg/kg BW, and 500 mg/kg BW of AML extract, and feeding was continued during the induction process. In the fourth group, 500 mg/kg BW AML extract treatment was started along with the cancer induction. The analyses were performed on the basis of the time period of in-tumour induction incidence, haematological parameters, histopathology and augmentation of TNF-α secretion and the NF-κB (p65 subunit) signalling pathway. The AML extract resisted and delayed tumour formation for up to 8 weeks in the 500 mg/kg BW pretreated group as compared to 4 weeks in the negative control group. The tumour burden varied in a dose-dependent manner in the different groups. On the 60th day, a significantly high burden (p < 0.001) was observed in the negative control group and the 100 mg/kg BW group. The study was validated by investigating the expression of TNF-α and the p65 subunit of the NF-κB signalling pathway, which were found to be reduced significantly in a dose-dependent manner and significantly reduced (p < 0.001) in the 500 mg/kg BW group as compared to negative control group. The 500 mg/kg BW pretreated group was found to have significant results in comparison to the 500 mg/kg BW post-treatment group. The study revealed the effective cancer preventive activity of Argemone mexicana Linn leaves (AML) in the mouse model and paved a pathway for molecular approaches which could be explored more in future studies.

The platinum coordination complex inhibits cell invasion-migration and epithelial-to-mesenchymal transition by altering the TGF-ß-SMAD pathway in colorectal cancer.

Introduction: There is a steady increase in colorectal cancer (CRC) incidences worldwide; at diagnosis, about 20 percent of cases show metastases. The transforming growth factor-beta (TGF-ß) signaling pathway is one of the critical pathways that influence the expression of cadherins allowing the epithelial-to-mesenchymal transition (EMT), which is involved in the progression of the normal colorectal epithelium to adenoma and metastatic carcinoma. The current study aimed to investigate the impact of a novel coordination complex of platinum (salicylaldiminato) PT(II) complex with dimethyl propylene linkage (PT-complex) on TGF-ß and EMT markers involved in the invasion and migration of the human HT-29 and SW620 CRC cell lines. Methods: Functional study and wound healing assay showed PT-complex significantly reduced cell motility and the migration and invasion of CRC cell lines compared to the untreated control. Western blot performed in the presence and absence of TGF-ß demonstrated that PT-complex significantly regulated the TGF-ß-mediated altered expressions of EMT markers. Results and Discussion: PT-complex attenuated the migration and invasion by upregulating the protein expression of EMT-suppressing factor E-cadherin and suppressing EMT-inducing factors such as N-Cadherin and Vimentin. Moreover, PT-complex significantly suppressed the activation of SMAD3 in both CRC cell lines. Further, the microarray data analysis revealed differential expression of genes related to invasion and migration. In conclusion, besides displaying antiproliferative activity, the PT complex can decrease the metastasis of CRC cell lines by modulating TGF-ß-regulated EMT markers. These findings provide new insight into TGF-ß/SMAD signaling as the molecular mechanism involved in the antitumoral properties of novel PT-complex.

Elucidation of the Anticancer Mechanism of Durian Fruit (Durio zibethinus) Pulp Extract in Human Leukemia (HL-60) Cancer Cells.

Durian (Durio zibethinus L.) grows widely in Southeast Asia. The pulp of the durian fruit contains carbohydrates, proteins, lipids, fibers, various vitamins, minerals, and fatty acids. This study was carried out to elucidate the anticancer mechanism of action of the methanolic extract of the fruit of Durio zibethinus (D. zibethinus) on human leukemia (HL-60) cells. The methanolic extract of D. zibethinus fruits exhibited its anticancer effect on HL-60 cells by inducing DNA damage and apoptosis. The DNA damage was confirmed by comet and DNA fragmentation assays. The methanolic extract of D. zibethinus fruits has been shown to cause cell cycle arrest in HL-60 cells during the S phase and G2/M phase. Additionally, the methanolic extract caused induction of the apoptotic pathway in the HL-60 cell line. This was confirmed by increased expression in pro-apoptotic proteins, viz., Bax protein expression, and a substantial reduction (p < 0.001) in anti-apoptotic proteins, viz., Bcl-2 and Bcl-xL expressions. Therefore, this study confirms that the methanolic extract of D. zibethinus exerts its anticancer effects on the HL-60 cell line, causing cell cycle arrest and induction of apoptosis by an intrinsic mechanism.

Design of novel quinazolinone derivatives as inhibitors for 5HT7 receptor.

To study the pharmacophore properties of quinazolinone derivatives as 5HT(7) inhibitors, 3D QSAR methodologies, namely Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) were applied, partial least square (PLS) analysis was performed and QSAR models were generated. The derived model showed good statistical reliability in terms of predicting the 5HT(7) inhibitory activity of the quinazolione derivative, based on molecular property fields like steric, electrostatic, hydrophobic, hydrogen bond donor and hydrogen bond acceptor fields. This is evident from statistical parameters like q(2) (cross validated correlation coefficient) of 0.642, 0.602 and r(2) (conventional correlation coefficient) of 0.937, 0.908 for CoMFA and CoMSIA respectively. The predictive ability of the models to determine 5HT(7) antagonistic activity is validated using a test set of 26 molecules that were not included in the training set and the predictive r(2) obtained for the test set was 0.512 & 0.541. Further, the results of the derived model are illustrated by means of contour maps, which give an insight into the interaction of the drug with the receptor. The molecular fields so obtained served as the basis for the design of twenty new ligands. In addition, ADME (Adsorption, Distribution, Metabolism and Elimination) have been calculated in order to predict the relevant pharmaceutical properties, and the results are in conformity with required drug like properties.

Molecular docking and 3D-QSAR studies on inhibitors of DNA damage signaling enzyme human PARP-1.

Poly (ADP-ribose) polymerase-1 (PARP-1) operates in a DNA damage signaling network. Molecular docking and three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on human PARP-1 inhibitors. Docked conformation obtained for each molecule was used as such for 3D-QSAR analysis. Molecules were divided into a training set and a test set randomly in four different ways, partial least square analysis was performed to obtain QSAR models using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Derived models showed good statistical reliability that is evident from their r², q²(loo) and r²(pred) values. To obtain a consensus for predictive ability from all the models, average regression coefficient r²(avg) was calculated. CoMFA and CoMSIA models showed a value of 0.930 and 0.936, respectively. Information obtained from the best 3D-QSAR model was applied for optimization of lead molecule and design of novel potential inhibitors.

Racial disparities in tissue plasminogen activator treatment rate for stroke: a population-based study.

BACKGROUND AND PURPOSE: Some prior studies have shown that racial disparities exist in intravenous tissue plasminogen activator (tPA) use for acute ischemic stroke. We sought to determine whether race was associated with tPA treatment for stroke in a predominantly black urban population. METHODS: Systematic chart abstraction was performed on consecutive hospitalized patients with ischemic stroke from all 7 acute care hospitals in the District of Columbia from February 1, 2008, to January 31, 2009. RESULTS: Of 1044 patients with ischemic stroke, 74% were black, 19% non-Hispanic white, and 5% received intravenous tPA. Blacks were one third less likely than whites to receive intravenous tPA (3% versus 10%, P<0.001). However, blacks were also less likely than whites to present within 3 hours of symptom onset (13% versus 21%, P=0.004) and also less likely to be tPA-eligible (5% versus 13%, P<0.001). Of those who presented within 3 hours, blacks were almost half as likely to be treated with intravenous tPA than whites (27% versus 46%, P=0.023). The treatment rate for tPA-eligible patients was similar for blacks and whites (70% versus 76%, P=0.62). CONCLUSIONS: In this predominantly black urban population hospitalized for acute ischemic stroke, blacks were significantly less likely to be treated with intravenous tPA due to contraindications to treatment, delayed presentation, and stroke severity. Effective interventions designed to increase treatment in this population need to focus on culturally relevant education programs designed to address barriers specific to this population.

Effect of trace elements on the seminal oxidative status and correlation to sperm motility in infertile Saudi males.

The impact of trace elements, especially zinc, selenium, copper, and magnesium, on male fertility has gained great interest and significance. Increased oxidative stress and altered trace element levels are probable etiological factors underlying male reproductive dysfunction and infertility. The present study focused on the evaluation of seminal oxidative markers, such as reactive oxygen species (ROS), malondialdehyde (MDA), and total antioxidant capacity (TAC), and trace element levels in the normozoospermic fertile control group (n = 40) and asthenozoospermic infertile group (n = 30). Semen from infertile men exhibited significantly higher ROS and MDA levels accompanied with significant decline in TAC and trace element (zinc and magnesium) levels. Furthermore, a significant correlation was observed between trace elements and oxidative markers with sperm motility. The current study revealed increased lipid peroxidation and oxidant-reductant imbalance that leads to deterioration of semen quality and male infertility. Thus, oxidative stress and trace elements can be considered important biomarkers of male infertility. Measurement of seminal oxidative stress with conventional seminological parameters must be integrated in fertility assessment from early stages to ensure healthy semen characteristics and fertility in men.

Selenium Nanoparticles by Moderating Oxidative Stress Promote Differentiation of Mesenchymal Stem Cells to Osteoblasts.

PURPOSE: Redox homeostasis plays an important role in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) for bone engineering. Oxidative stress (OS) is believed to induce osteoporosis by changing bone homeostasis. Selenium nanoparticles (SeNPs), an antioxidant with pleiotropic pharmacological activity, prevent bone loss. However, the molecular mechanism underlying the osteogenic activity during hMSC-SeNP interaction is unclear. METHODS: This study assessed the effects of different concentrations (25, 50, 100, and 300 ng/mL) of SeNPs on the cell viability and differentiation ability of human embryonic stem cell-derived hMSCs. In addition, we analyzed OS markers and their effect on mitogen-activated protein kinase (MAPK) and Forkhead box O3 (FOXO3) during osteogenesis. RESULTS: SeNPs increased the cell viability of hMSCs and induced their differentiation toward an osteogenic over an adipogenic lineage by enhancing osteogenic transcription and mineralization, while inhibiting Nile red staining and adipogenic gene expression. By preventing excessive reactive oxygen species accumulation, SeNPs increased antioxidant levels in hMSCs undergoing osteogenesis compared to untreated cells. In addition, SeNPs significantly upregulated the gene and protein expression of phosphorylated c-Jun N-terminal kinase (JNK) and FOXO3a, with no significant change in the expression levels of extracellular signal-related kinase (ERK) and p38 MAPK. CONCLUSION: The results approved that low concentrations of SeNPs might enhance the cell viability and osteogenic potential of hMSCs by moderating OS. Increased JNK and FOXO3a expression shows that SeNPs might enhance osteogenesis via activation of the JNK/FOXO3 pathway. In addition, SeNP co-supplementation might prevent bone loss by enhancing osteogenesis and, thus, can be an effective candidate for treating osteoporosis through cell-based therapy.

Glutathione and oxidized nicotinamide adenine dinucleotide (NAD+) redox status in plasma and placental tissue of Saudi patients with intrauterine growth restriction.

OBJECTIVES: To assess the oxidation state and gene expression profiles of relevant enzymes in intrauterine growth restriction (IUGR) patients in Saudi Arabia. METHODS: Current case-control study involved plasma and placental tissue samples from 25 IUGR patients and 25 healthy pregnant (HP) women attending the Obstetrics and Gynecology Clinic, King Khalid University Hospital, Riyadh, Saudi Arabia, between April and November 2017. We compared hydrogen peroxide, superoxide anions, malondialdehyde, and oxidative stress markers levels and the activities of glutathione-related enzymes (glutathione peroxidase [GPx], glutathione reductase [GR], glutathione S-transferase [GST], glutamate cysteine ligase [GCL], glutathione synthetase [GS], reduced glutathione [GSH], oxidized glutathione [GSSG], and oxidized nicotinamide adenine dinucleotide [NAD+], and reduced NAD [NADH]) between the 2 groups. We also compared differential expression levels of glutathione-related enzyme genes using reverse transcription-quantitative polymerase chain reaction. RESULTS: Oxidative stress markers significantly differed in IUGR samples, while GSH levels and GPx, GR, GST, GCL, and GS activities and their placental mRNA transcriptional levels were significantly lower. Plasma and placental NAD+ levels were also significantly lower, while NADH levels were significantly higher, causing lowered NAD+-NADH ratios in the IUGR group compared to control. CONCLUSIONS: Intrauterine growth restriction patients show a metabolic shift in favor of oxidation compared to HP women.