Fabrication and characterization of a new eco-friendly sulfonamide-chitosan derivative with enhanced antimicrobial and selective cytotoxicity properties.

Chitosan (CH) exhibits low antimicrobial activity. This study addresses this issue by modifying the chitosan with a sulfonamide derivative, 3-(4-(N,N-dimethylsulfonyl)phenyl)acrylic acid. The structure of the sulfonamide-chitosan derivative (DMS-CH) was confirmed using Fourier transform infrared spectroscopy and Nuclear magnetic resonance. The results of scanning electron microscopy, thermal gravimetric analysis, and X-ray diffraction indicated that the morphology changed to a porous nature, the thermal stability decreased, and the crystallinity increased in the DMS-CH derivative compared to chitosan, respectively. The degree of substitution was calculated from the elemental analysis data and was found to be moderate (42%). The modified chitosan exhibited enhanced antimicrobial properties at low concentrations, with a minimum inhibitory concentration (MIC) of 50 µg/mL observed for B. subtilis and P. aeruginosa, and a value of 25 µg/mL for S. aureus, E. coli, and C. albicans. In the case of native chitosan, the MIC values doubled or more, with 50 µg/mL recorded for E. coli and C. albicans and 100 µg/mL recorded for B. subtilis, S. aureus, and P. aeruginosa. Furthermore, toxicological examinations conducted on MCF-7 (breast adenocarcinoma) cell lines demonstrated that DMS-CH exhibited greater toxicity (IC50 = 225.47 µg/mL) than pure CH, while still maintaining significant safety limits against normal lung fibroblasts (WI-38). Collectively, these results suggest the potential use of the newly modified chitosan in biomedical applications.

Targeting Autophagy, Apoptosis, and Oxidative Perturbations with Dapagliflozin Mitigates Cadmium-Induced Cognitive Dysfunction in Rats.

Cognitive decline and Alzheimer-like neuropathology are common manifestations of cadmium toxicity. Thanks to its antioxidant/anti-apoptotic features, dapagliflozin has demonstrated promising neuroprotective actions. However, its effect on cadmium-induced neurotoxicity is lacking. The present work aimed to examine whether dapagliflozin could protect rats from cadmium-evoked cognitive decline. In this study, the behavioral disturbances and hippocampal biomolecular alterations were studied after receiving dapagliflozin. Herein, cadmium-induced memory/learning decline was rescued in the Morris water maze, novel object recognition task, and Y-shaped maze by dapagliflozin. Meanwhile, the hippocampal histopathological abnormalities were mitigated. The molecular mechanisms revealed that dapagliflozin lowered hippocampal expression of p-tau and Aß42 neurotoxic proteins while augmenting acetylcholine. The cognitive enhancement was triggered by hippocampal autophagy stimulation, as indicated by decreased SQSTM-1/p62 and Beclin 1 upregulation. Meanwhile, a decrease in p-mTOR/total mTOR and an increase in p-AMPK/total AMPK ratio were observed in response to dapagliflozin, reflecting AMPK/mTOR cascade stimulation. Dapagliflozin, on the other hand, dampened the pro-apoptotic processes in the hippocampus by downregulating Bax, upregulating Bcl-2, and inactivating GSK-3ß. The hippocampal oxidative insult was mitigated by dapagliflozin as seen by lipid peroxide lowering, antioxidants augmentation, and SIRT1/Nrf2/HO-1 pathway activation. In conclusion, dapagliflozin's promising neuroprotection was triggered by its pro-autophagic, anti-apoptotic, and antioxidant properties.

Targeting Autophagy, Apoptosis, and SIRT1/Nrf2 Axis with Topiramate Underlies Its Neuroprotective Effect against Cadmium-Evoked Cognitive Deficits in Rats.

Cadmium is an environmental toxicant that instigates cognitive deficits with excessive glutamate excitatory neuroactivity in the brain. Topiramate, a glutamate receptor antagonist, has displayed favorable neuroprotection against epilepsy, cerebral ischemia, and Huntington's disease; however, its effect on cadmium neurotoxicity remains to be investigated. In this study, topiramate was tested for its potential to combat the cognitive deficits induced by cadmium in rats with an emphasis on hippocampal oxidative insult, apoptosis, and autophagy. After topiramate intake (50 mg/kg/day; p.o.) for 8 weeks, behavioral disturbances and molecular changes in the hippocampal area were explored. Herein, Morris water maze, Y-maze, and novel object recognition test revealed that topiramate rescued cadmium-induced memory/learning deficits. Moreover, topiramate significantly lowered hippocampal histopathological damage scores. Mechanistically, topiramate significantly replenished hippocampal GLP-1 and dampened Aß42 and p-tau neurotoxic cues. Notably, it significantly diminished hippocampal glutamate content and enhanced acetylcholine and GABA neurotransmitters. The behavioral recovery was prompted by hippocampal suppression of the pro-oxidant events with notable activation of SIRT1/Nrf2/HO-1 axis. Moreover, topiramate inactivated GSK-3ß and dampened the hippocampal apoptotic changes. In tandem, stimulation of hippocampal pro-autophagy events, including Beclin 1 upregulation, was triggered by topiramate that also activated AMPK/mTOR pathway. Together, the pro-autophagic, antioxidant, and anti-apoptotic features of topiramate contributed to its neuroprotective properties in rats intoxicated with cadmium. Therefore, it may be useful to mitigate cadmium-induced cognitive deficits.

SELF-EXPANDING FOAM VS PRE-PERITONEAL PACKING FOR EXSANGUINATING PELVIC HEMORRHAGE.

BACKGROUND: Mortality for pelvic fracture patients presenting with hemorrhagic shock ranges from 21-57%. The objective of this study was to develop a lethal and clinically-relevant pelvic hemorrhage animal model with and without bony fracture for evaluating therapeutic interventions. ResQFoam is a self-expanding foam that has previously been described to significantly decrease mortality in large-animal models of abdominal exsanguination. We hypothesized that administration of ResQFoam into the pre-peritoneal space could decrease mortality in exsanguinating pelvic hemorrhage. METHODS: Two pelvic hemorrhage models were developed using non-coagulopathic swine. Pelvic hemorrhage model #1: bilateral, closed-cavity, major vascular retro-peritoneal hemorrhage without bony pelvic fracture. After injury, animals received no treatment (control, n = 10), underwent pre-peritoneal packing using laparotomy pads (n = 11), or received ResQFoam (n = 10) injected into the pre-peritoneal space. Pelvic hemorrhage model #2: unilateral, closed-cavity, retro-peritoneal hemorrhage injury (with intra-peritoneal communication) combined with complex pelvic fracture. After injury, animals received resuscitation (control, n = 12), resuscitation with pre-peritoneal packing (n = 10) or with ResQFoam injection (n = 10) into the pre-peritoneal space. RESULTS: For model #1, only ResQFoam provided a significant survival benefit. The median survival times were 50 and 67 minutes for pre-peritoneal packing and ResQFoam, compared to 6 minutes with controls (p = 0.002 and 0.057, respectively). Foam treatment facilitated hemodynamic stabilization and resulted in significantly less hemorrhage (21.5 ± 5.3 g/kg) relative to controls (31.6 ± 5.0 g/kg, p < 0.001) and pre-peritoneal packing (32.7 ± 5.4 g/kg, p < 0.001). For model #2, both ResQFoam and pre-peritoneal packing resulted in significant survival benefit compared to controls. The median survival times were 119 and 124 minutes for the pre-peritoneal packing and ResQFoam groups, compared to 4 minutes with controls (p = 0.004 and 0.013, respectively). CONCLUSIONS: Percutaneous injection of ResQFoam into the pre-peritoneal space improved survival relative to controls, and similar survival benefit was achieved compared to standard pre-peritoneal pelvic packing. The technology has potential to augment the armamentarium of tools to treat pelvic hemorrhage.Study Type: This is a Basic Science paper and, therefore, does not require level of evidence.

Neuroprotective Impact of Linagliptin against Cadmium-Induced Cognitive Impairment and Neuropathological Aberrations: Targeting SIRT1/Nrf2 Axis, Apoptosis, and Autophagy.

Cadmium is an environmental contaminant associated with marked neurotoxicity and cognitive impairment. Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, has demonstrated promising neuroprotection against cerebral ischemia and diabetic dementia. However, there has been no study of its effect on cadmium-induced cognitive deficits. In the present work, linagliptin's prospective neuroprotective effects against cadmium-evoked cognitive decline were examined in vivo in rats. The molecular pathways related to oxidative stress, apoptosis, and autophagy were investigated. Histology, immunohistochemistry, ELISA, and biochemical assays were performed on brain hippocampi after receiving linagliptin (5 mg/kg/day). The current findings revealed that cadmium-induced learning and memory impairment were improved by linagliptin as seen in the Morris water maze, Y-maze, and novel object recognition test. Moreover, linagliptin lowered hippocampal neurodegeneration as seen in histopathology. At the molecular level, linagliptin curtailed hippocampal DPP-4 and augmented GLP-1 levels, triggering dampening of the hippocampal neurotoxic signals Aß42 and p-tau in rats. Meanwhile, it enhanced hippocampal acetylcholine and GABA and diminished the glutamate spike. The behavioral recovery was associated with dampening of the hippocampal pro-oxidant response alongside SIRT1/Nrf2/HO-1 axis stimulation. Meanwhile, linagliptin counteracted hippocampal apoptosis markers and inhibited the pro-apoptotic kinase GSK-3ß. In tandem, linagliptin activated hippocampal autophagy by lowering SQSTM-1/p62 accumulation, upregulating Beclin 1, and stimulating AMPK/mTOR pathway. In conclusion, linagliptin's antioxidant, antiapoptotic, and pro-autophagic properties advocated its promising neuroprotective impact. Thus, linagliptin may serve as a management approach against cadmium-induced cognitive deficits.

Transobturator Tension-Free Vaginal Flap Operation versus Synthetic Transobturator Tape for Treatment of Female Stress Urinary Incontinence: A Prospective Randomized Study.

INTRODUCTION: Synthetic mid-urethral slings (MUSs) are the gold standard treatment for female stress urinary incontinence (SUI). Recently, there have been reports of serious adverse events with synthetic tapes such as urethral erosion, vaginal erosion, and mesh infection. Tension-free vaginal flap (TVF) operation has been proven to be successful as a natural alternative to synthetic slings. We propose our novel technique, the transobturator tension-free vaginal flap (TO-TVF), utilizing native vaginal tissue and being suspended via transobturator route. METHODS: This prospective study was conducted on 72 female patients with SUI, presenting at Alexandria University Hospital. Patients were randomized into 2 groups, group 1: 37 patients subjected to TO-TVF and group 2: 35 patients to conventional transobturator tape (TOT). In TO-TVF, a rectangular vaginal wall flap is created. A polypropylene monofilament mesh is sutured to each edge of the vaginal flap. This is inserted like conventional outside-in TOT. Patients were subjected to PGI and UDI-6 questionnaires and urodynamic study before and 6 months postoperatively. RESULTS: Both groups showed comparable and significant improvements in questionnaires. Mean operative time for TO-TVF and conventional TOT was 26.31 ± 5.2 min and 21.8 ± 3.1 min, respectively. Cure rate was 89% in group 1 and 91.4% in group 2, which was not statistically significant. No significant intraoperative complications were encountered. We had no cases of vaginal or urethral erosion in both groups. CONCLUSIONS: TO-TVF is a cost-effective, feasible, safe, and effective surgical alternative to synthetic MUS. Synthetic mesh tissue anchoring properties are maintained for better adjustment of tension. However, long-term follow-up on a large cohort of patients is still needed.

Stimulation of Autophagy by Dapagliflozin Mitigates Cadmium-Induced Testicular Dysfunction in Rats: The Role of AMPK/mTOR and SIRT1/Nrf2/HO-1 Pathways.

Cadmium (Cd) is a widespread environmental pollutant that triggers testicular dysfunction. Dapagliflozin is a selective sodium-glucose co-transporter-2 inhibitor with notable antioxidant and anti-apoptotic features. It has shown marked cardio-, reno-, hepato-, and neuroprotective effects. Yet, its effect on Cd-evoked testicular impairment has not been examined. Hence, the goal of the current study was to investigate the potential positive effect of dapagliflozin against Cd-induced testicular dysfunction in rats, with an emphasis on autophagy, apoptosis, and oxidative insult. Dapagliflozin (1 mg/kg/day) was given by oral gavage, and testicular dysfunction, impaired spermatogenesis, and biomolecular events were studied via immunohistochemistry, histopathology, and ELISA. The current findings demonstrated that dapagliflozin improved relative testicular weight, serum testosterone, and sperm count/motility and reduced sperm abnormalities, signifying mitigation of testicular impairment and spermatogenesis disruption. Moreover, dapagliflozin attenuated Cd-induced histological abnormalities and preserved testicular structure. The testicular function recovery was prompted by stimulating the cytoprotective SIRT1/Nrf2/HO-1 axis, lowering the testicular oxidative changes, and augmenting cellular antioxidants. As regards apoptosis, dapagliflozin counteracted the apoptotic machinery by downregulating the pro-apoptotic signals together with Bcl-2 upregulation. Meanwhile, dapagliflozin reactivated the impaired autophagy, as seen by a lowered accumulation of SQSTM-1/p62 and Beclin 1 upregulation. In the same context, the testicular AMPK/mTOR pathway was stimulated as evidenced by the increased p-AMPK (Ser487)/total AMPK ratio alongside the lowered p-mTOR (Ser2448)/total mTOR ratio. Together, the favorable mitigation of Cd-induced testicular impairment/disrupted spermatogenesis was driven by the antioxidant, anti-apoptotic, and pro-autophagic actions of dapagliflozin. Thus, it could serve as a tool for the management of Cd-evoked testicular dysfunction.

Synthesis, characterization, and biological evaluation of new chitosan derivative bearing diphenyl pyrazole moiety.

This work reports the synthesis of a new pyrazole derivative by reacting 5-amino-1,3-diphenyl pyrazole with succinic anhydride and bearing the product chemically on the chitosan chains via amide linkage to achieve a new chitosan derivative (DPPS-CH). The prepared chitosan derivative was analyzed by IR, NMR, elemental analysis, XRD, TGA-DTG, and SEM. As compared with chitosan, DPPS-CH showed an amorphous and porous structure. Coats-Redfern results showed that the thermal activation energy for the first decomposition of DPPS-CH is 43.72 KJ mol-1 lower than that required for chitosan (88.32 KJ mol-1), indicating the accelerating effect of DPPS on the thermal decomposition of DPPS-CH. The DPPS-CH manifested a powerful wide spectrum antimicrobial potential against pathogenic gram-positive and gram-negative bacteria and Candida albicans at minute concentrations (MIC = 50 µg mL-1) compared to chitosan (MIC = 100 µg mL-1). The MTT assay proved the toxic properties of DPPS-CH against a cancer cell line (MCF-7) at a minute concentration (IC50 = 15.14 µg mL-1) while affecting normal cells (WI-38) at seven times this concentration (IC50 = 107.8 µg mL-1). According to the current findings, the chitosan derivative developed in this work appears to be a promising material for use in biological domains.

Exploring the antimicrobial, antioxidant, anticancer, biocompatibility, and larvicidal activities of selenium nanoparticles fabricated by endophytic fungal strain Penicillium verhagenii.

Herein, four endophytic fungal strains living in healthy roots of garlic were used to produce selenium nanoparticles (Se-NPs) via green synthesis. Penicillium verhagenii was found to be the most efficient Se-NPs producer with a ruby red color that showed maximum surface plasmon resonance at 270 nm. The as-formed Se-NPs were crystalline, spherical, and well-arranged without aggregation, and ranged from 25 to 75 nm in size with a zeta potential value of -32 mV, indicating high stability. Concentration-dependent biomedical activities of the P. verhagenii-based Se-NPs were observed, including promising antimicrobial activity against different pathogens (Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Candida albicans, C. glabrata, C. tropicalis, and C. parapsilosis) with minimum inhibitory concentration (MIC) of 12.5-100 µg mL-1. The biosynthesized Se-NPs showed high antioxidant activity with DPPH-scavenging percentages of 86.8 ± 0.6% at a concentration of 1000 µg mL-1 and decreased to 19.3 ± 4.5% at 1.95 µg mL-1. Interestingly, the Se-NPs also showed anticancer activity against PC3 and MCF7 cell lines with IC50 of 225.7 ± 3.6 and 283.8 ± 7.5 µg mL-1, respectively while it is remaining biocompatible with normal WI38 and Vero cell lines. Additionally, the green synthesized Se-NPs were effective against instar larvae of a medical insect, Aedes albopictus with maximum mortality of 85.1 ± 3.1, 67.2 ± 1.2, 62.10 ± 1.4, and 51.0 ± 1.0% at a concentration of 50 µg mL-1 for I, II, III, and IV-instar larva, respectively. These data highlight the efficacy of endophytic fungal strains for cost-effective and eco-friendly Se-NPs synthesis with different applications.

Management of pediatric blunt abdominal trauma with split liver or spleen injuries: a retrospective study.

BACKGROUND: Blunt abdominal trauma is a prevailing cause of pediatric morbidity and mortality. It constitutes the most frequent type of pediatric injuries. Contrast-enhanced sonography (CEUS) and contrast-enhanced computed tomography (CECT) are considered pivotal diagnostic modalities in hemodynamically stable patients. AIM: To report the experience in management of pediatric split liver and spleen injuries using CEUS and CECT. PATIENTS AND METHODS: This study included 246 children who sustained blunt abdominal trauma, and admitted and treated at three tertiary hospitals in the period of 5 years. Primary resuscitation was offered to all children based on the advanced trauma and life support (ATLS) protocol. A special algorithm for decision-making was followed. It incorporated the FAST, baseline ultrasound (US), CEUS, and CECT. Patients were treated according to the imaging findings and hemodynamic stability. RESULTS: All 246 children who sustained a blunt abdominal were studied. Patients' age was 10.5 ± 2.1. Road traffic accidents were the most common cause of trauma; 155 patients (63%). CECT showed the extent of injury in 153 patients' spleen (62%) and 78 patients' liver (32%), while the remaining 15 (6%) patients had both injuries. CEUS detected 142 (57.7%) spleen injury, and 67 (27.2%) liver injury. CONCLUSIONS: CEUS may be a useful diagnostic tool among hemodynamically stable children who sustained low-to-moderate energy isolated blunt abdominal trauma. It may be also helpful for further evaluation of uncertain CECT findings and follow-up of conservatively managed traumatic injuries.

Combined anterior and posterior ring fixation versus posterior ring fixation alone in the management of unstable Tile B and C pelvic ring injuries: A randomized controlled trial.

PURPOSE: Combined anterior and posterior ring (APR) fixation is classically performed in Tile B2 and C1 injuries to achieve superior biomechanical stability. However, the posterior ring (PR) is the main weight bearing portion that is responsible for weight transmission from the upper parts of the body to the lower limbs through the sacrum and the linea terminalis. It is hypothesized that isolated PR fixation can achieve comparable radiological and clinical outcomes to APR fixation. Therefore, we conducted this study to compare the two fixation principles in managing Tile B2 and C1 injuries. METHODS: Our study included 20 patients with Tile B2 injuries and 20 patients with Tile C1 injuries. This study was a randomized control single-blinded study via computerized random numbers with a 1:1 allocation by using random block method. The study was performed at a level one trauma center. A total of 40 patients with Tile B2 and C1 injuries underwent combined APR or isolated PR fixation (Group A and B, respectively). Matta & Tornetta radiological principles and Majeed pelvic scoring system were used for the assessment of primary outcomes and postoperative complications. Secondary outcomes included operative time, amount of blood loss, intraoperative assessment of reduction, need of another operation, length of hospital stay, ability to weight bear postoperatively and pain control metrics. We used student t-test to compare the difference in means between two groups, and Chi-square test to compare proportions between two qualitative parameters. We set the confidence interval to 95% and the margin of error accepted to 5%. So, p ≤ 0.05 was considered statistically significant. RESULTS: The mean follow-up duration was 18 months. The operative time (mean difference 0.575 h) and the intraoperative blood loss (mean difference 97.5 mL) were lower in Group B. Also, despite the higher frequency of rami displacement before union in the same group, there were no significant differences in terms of radiological outcome (excellent outcome with OR = 2.357), clinical outcome (excellent outcome with OR = 2.852) and postoperative complications assessment (OR = 1.556) at last follow-up. CONCLUSION: The authors concluded that isolated PR fixation could favorably manage Tile B2 and C1 pelvic ring injuries with Nakatani zone II pubic rami fractures and intact inguinal ligament. Its final radiological and clinical outcomes and postoperative complications were comparable to combined APR fixation, but with less morbidity (shorter operation time, lower amount of blood, and no records of postoperative wound infection).

Biomechanics of hamstring tendon, quadriceps tendon, and bone-patellar tendon-bone grafts for anterior cruciate ligament reconstruction: a cadaveric study.

PURPOSE: The three most commonly used autografts for anterior cruciate ligament reconstruction (ACL) are: bone-patellar tendon-bone (BTB), hamstring tendons (HT), and quadriceps tendon (QT). A cadaveric study was performed to determine if there were any differences in mechanical and structural properties under biomechanical testing. METHODS: Twenty-seven graft specimens were harvested from 9 human cadaveric legs. Mean donor age was 75.2 years (range 53-85 years). Twenty-two specimens (8 HT, 7 QT, and 7 BTB) completed cyclic preconditioning from 50 to 800 N for 200 cycles and a load to failure test at an extension rate of 1 mm/s. Structural and mechanical properties of BTB, HT, and QT grafts were compared using a one-way ANOVA and Tukey's honest significant difference. RESULTS: There was no difference in the ultimate load to failure (N) across all 3 graft types (p = 0.951). Quadriceps tendon demonstrated greater cross-sectional area (mm2) when compared to both HT and BTB (p = 0.001) and was significantly stiffer (N/mm) than HT but not BTB (p = 0.004). Stress (N/mm2) of the HT at ultimate load was greater than QT but not BTB (p = 0.036). Elastic modulus (MPa) of HT was greater than both QT and BTB (p = 0.016). CONCLUSION: There was no difference in the ultimate load to failure of BTB, HT, and QT grafts harvested from the same specimens. All 3 grafts had similar loads to failure with a significant increase in stiffness when compared to the native ACL. Furthermore, QT demonstrated more favourable structural properties compared to HT and BTB with greater cross-sectional area to both HT and BTB and greater stiffness compared to HT.

New thiadiazole modified chitosan derivative to control the growth of human pathogenic microbes and cancer cell lines.

The emergence of multidrug-resistant microbes and the propagation of cancer cells are global health issues. The unique properties of chitosan and its derivatives make it an important candidate for therapeutic applications. Herein, a new thiadiazole derivative, 4-((5-(butylthio)-1,3,4-thiadiazol-2-yl) amino)-4-oxo butanoic acid (BuTD-COOH) was synthesized and used to modify the chitosan through amide linkages, forming a new thiadiazole chitosan derivative (BuTD-CH). The formation of thiadiazole and the chitosan derivative was confirmed by FT-IR, 1H/13C-NMR, GC-MS, TGA, Elemental analysis, and XPS. The BuTD-CH showed a high antimicrobial effect against human pathogens Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Candida albicans with low MIC values of 25-50 µg ml-1 compared to unmodified chitosan. The in-vitro cytotoxicity of BuTD-CH was evaluated against two cancer cell lines (MCF-7 and HepG2) and one normal cell (HFB4) using the MTT method. The newly synthesized derivatives showed high efficacy against cancerous cells and targeted them at low concentrations (IC50 was 178.9 ± 9.1 and 147.8 ± 10.5 µg ml-1 for MCF-7 and HepG2, respectively) compared with normal HFB4 cells (IC50 was 335.7 ± 11.4 µg ml-1). Thus, low concentrations of newly synthesized BuTD-CH could be safely used as an antimicrobial and pharmacological agent for inhibiting the growth of human pathogenic microbes and hepatocellular and adenocarcinoma therapy.

Topiramate Reprofiling for the Attenuation of Cadmium-Induced Testicular Impairment in Rats: Role of NLRP3 Inflammasome and AMPK/mTOR-Linked Autophagy.

Topiramate, a promising drug classically used for the management of neurological disorders including epilepsy and migraine, has demonstrated marked anti-inflammatory and anti-apoptotic actions in murine models of cardiac post-infarction inflammation, wound healing, and gastric/intestinal injury. However, its potential impact on cadmium-induced testicular injury remains to be elucidated. Herein, the present study aimed to explore the effect of topiramate against cadmium-invoked testicular impairment with emphasis on the molecular mechanisms linked to inflammation, apoptosis, and autophagy. Herein, administration of topiramate (50 mg/kg/day, by gavage) continued for 60 days and the testes were examined by histology, immunohistochemistry, and biochemical assays. The present data demonstrated that serum testosterone, sperm count/abnormalities, relative testicular weight, and histopathological aberrations were improved by topiramate administration to cadmium-intoxicated rats. The rescue of testicular dysfunction was driven by multi-pronged mechanisms including suppression of NLRP3/caspase-1/IL-1ß cascade, which was evidenced by dampened caspase-1 activity, lowered IL-1ß/IL-18 production, and decreased nuclear levels of activated NF-κBp65. Moreover, curbing testicular apoptosis was seen by lowered Bax expression, decreased caspase-3 activity, and upregulation of Bcl-2. In tandem, testicular autophagy was activated as seen by diminished p62 SQSTM1 accumulation alongside Beclin-1 upregulation. Autophagy activation was associated with AMPK/mTOR pathway stimulation demonstrated by decreased mTOR (Ser2448) phosphorylation and increased AMPK (Ser487) phosphorylation. In conclusion, combating inflammation/apoptosis and enhancing autophagic events by topiramate were engaged in ameliorating cadmium-induced testicular impairment.

Alleviate the Drought Stress on Triticum aestivum L. Using the Algal Extracts of Sargassum latifolium and Corallina elongate Versus the Commercial Algal Products.

Herein, two seaweed extracts (Sargassum latifolium and Corallina elongate), and two commercial seaweed products (Canada power and Oligo-X) with a concentration of 5% were used to alleviate the drought stress on wheat plants. The extract of C. elongate had the highest capacity to ameliorate the deleterious effects of water scarcity followed by S. latifolium and the commercial products. The drought stress reduced wheat shoots length and the contents of pigments (chlorophyll and carotenoids), carbohydrates, and proteins. While the highest increment in the total carbohydrates and protein contents of the wheat shoot after two stages, 37-and 67-days-old, were noted in drought-stressed plants treated with C. elongate extract with values of (34.6% and 22.8%) and (51.9% and 39.5%), respectively, compared to unstressed plants. Decreasing the activity of antioxidant enzymes, peroxidase, superoxidase dismutase, and polyphenol oxidase in drought-stressed plants treated with algal extracts indicated amelioration of the response actions. Analysis of phytohormones in wheat plants exhibited increasing GA3 and IAA contents with percentages of (20.3-13.8%) and (72.7-25%), respectively. Interestingly, all morphological and metabolic characteristics of yield were improved due to the algal treatments compared with untreated drought-stressed plants. Overall, the algal extracts, especially those from seaweed of C. elongate, could represent a sustainable candidate to overcome the damage effects of water deficiency in the wheat plant.

Repositioning Linagliptin for the Mitigation of Cadmium-Induced Testicular Dysfunction in Rats: Targeting HMGB1/TLR4/NLRP3 Axis and Autophagy.

Cadmium, a ubiquitous environmental toxicant, disrupts testicular function and fertility. The dipeptidyl peptidase-4 inhibitor linagliptin has shown pronounced anti-inflammatory and anti-apoptotic features; however, its effects against cadmium-evoked testicular impairment have not been examined. Herein, the present study investigated targeting inflammation, apoptosis, and autophagy by linagliptin for potential modulation of cadmium-induced testicular dysfunction in rats. After 60 days of cadmium chloride administration (5 mg/kg/day, by gavage), testes, epididymis, and blood were collected for analysis. The present findings revealed that linagliptin improved the histopathological lesions, including spermatogenesis impairment and germ cell loss. Moreover, it improved sperm count/motility and serum testosterone. The favorable effects of linagliptin were mediated by curbing testicular inflammation seen by dampening of HMGB1/TLR4 pathway and associated lowering of nuclear NF-κBp65. In tandem, linagliptin suppressed the activation of NLRP3 inflammasome/caspase 1 axis with consequent lowering of the pro-inflammatory IL-1ß and IL-18. Jointly, linagliptin attenuated testicular apoptotic responses seen by Bax downregulation, Bcl-2 upregulation, and suppressed caspase 3 activity. With respect to autophagy, linagliptin enhanced the testicular autophagy flux seen by lowered accumulation of p62 SQSTM1 alongside upregulation of Beclin 1. The observed autophagy stimulation was associated with elevated AMPK (Ser487) phosphorylation and lowered mTOR (Ser2448) phosphorylation, indicating AMPK/mTOR pathway activation. In conclusion, inhibition of testicular HMGB1/TLR4/NLRP3 pro-inflammatory axis and apoptosis alongside stimulation of autophagy were implicated in the favorable actions of linagliptin against cadmium-triggered testicular impairment.

Light enhanced the antimicrobial, anticancer, and catalytic activities of selenium nanoparticles fabricated by endophytic fungal strain, Penicillium crustosum EP-1.

Selenium nanoparticles (Se-NPs) has recently received great attention over owing to their superior optical properties and wide biological and biomedical applications. Herein, crystallographic and dispersed spherical Se-NPs were green synthesized using endophytic fungal strain, Penicillium crustosum EP-1. The antimicrobial, anticancer, and catalytic activities of biosynthesized Se-NPs were investigated under dark and light (using Halogen tungsten lamp, 100 Watt, λ > 420 nm, and light intensity of 2.87 W m-2) conditions. The effect of Se-NPs was dose dependent and higher activities against Gram-positive and Gram-negative bacteria as well different Candida spp. were attained in the presence of light than obtained under dark conditions. Moreover, the viabilities of two cancer cells (T47D and HepG2) were highly decreased from 95.8 ± 2.9% and 93.4 ± 3.2% in dark than those of 84.8 ± 2.9% and 46.4 ± 3.3% under light-irradiation conditions, respectively. Significant decreases in IC50 values of Se-NPs against T47D and HepG2 were obtained at 109.1 ± 3.8 and 70.4 ± 2.5 µg mL-1, respectively in dark conditions than 19.7 ± 7.2 and 4.8 ± 4.2 µg mL-1, respectively after exposure to light-irradiation. The photoluminescence activity of Se-NPs revealed methylene blue degradation efficiency of 89.1 ± 2.1% after 210 min under UV-irradiation compared to 59.7 ± 0.2% and 68.1 ± 1.03% in dark and light conditions, respectively. Moreover, superior stability and efficient MB degradation efficiency were successfully achieved for at least five cycles.

Enhanced Antimicrobial, Cytotoxicity, Larvicidal, and Repellence Activities of Brown Algae, Cystoseira crinita-Mediated Green Synthesis of Magnesium Oxide Nanoparticles.

Herein, the metabolites secreted by brown algae, Cystoseira crinita, were used as biocatalyst for green synthesis of magnesium oxide nanoparticles (MgO-NPs). The fabricated MgO-NPs were characterized using UV-vis spectroscopy, Fourier transforms infrared spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy linked with energy-dispersive X-ray (SEM-EDX), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Data showed successful formation of crystallographic and spherical MgO-NPs with sizes of 3-18 nm at a maximum surface plasmon resonance of 320 nm. Moreover, EDX analysis confirms the presence of Mg and O in the sample with weight percentages of 54.1% and 20.6%, respectively. Phyco-fabricated MgO-NPs showed promising activities against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans with MIC values ranging between 12.5 and 50 µg mL-1. The IC50 value of MgO-NPs against cancer cell lines (Caco-2) was 113.4 µg mL-1, whereas it was 141.2 µg mL-1 for normal cell lines (Vero cell). Interestingly, the green synthesized MgO-NPs exhibited significant larvicidal and pupicidal activity against Musca domestica. At 10 µg mL-1 MgO-NPs, the highest mortality percentages were 99.0%, 95.0%, 92.2%, and 81.0% for I, II, III instars' larvae, and pupa of M. domestica, respectively, with LC50 values (3.08, 3.49, and 4.46 µg mL-1), and LC90 values (7.46, 8.89, and 10.43 µg mL-1), respectively. Also, MgO-NPs showed repellence activity for adults of M. domestica at 10 µg mL-1 with 63.0%, 77.9%, 84.9%, and 96.8% after 12, 24, 48, and 72 h, respectively.

Targeting oxidative stress, apoptosis, and autophagy by galangin mitigates cadmium-induced renal damage: Role of SIRT1/Nrf2 and AMPK/mTOR pathways.

BACKGROUND: Galangin, a bioactive flavonoid with remarkable antioxidant and anti-apoptotic actions, has demonstrated promising amelioration of experimental hepatotoxicity, cardiomyopathy, and colitis. Yet, its impact on cadmium-induced renal injury has not been explored. Herein, we aimed at exploring the potential of galangin to attenuate cadmium-induced nephrotoxicity in rats, focusing on oxidative stress, apoptosis, and autophagy. METHODOLOGY: Cadmium chloride (5 mg/kg/day) and galangin (15 mg/kg/day) were received by oral gavage and the kidney tissues were inspected using ELISA, biochemical measurements, histology, and immunohistochemistry. KEY FINDINGS: Galangin attenuated cadmium-induced renal damage by diminishing the histopathological alterations alongside KIM-1, BUN, and creatinine. At the molecular level, galangin attenuated the oxidative insult by significantly lowering the lipid peroxides and NOX-1 and augmenting GSH and GPx antioxidants. It also activated the cytoprotective SIRT1/Nrf2/HO-1 pathway by significantly upregulating the protein expression of SIRT1, Nrf2, and HO-1. Consistently, galangin suppressed renal apoptotic cell death by significantly lowering the protein expression of Bax and cytochrome C and activity of caspase-3 alongside upregulating the protein expression of the anti-apoptotic Bcl-2. Additionally, galangin activated the impaired autophagy flux as seen by diminishing the accumulation of SQSTM1/p62 and increasing the protein expression of Beclin 1. Meanwhile, galangin stimulated the autophagy-linked AMPK/mTOR pathway by significantly increasing the p-AMPK/total AMPK and lowering p-mTOR/total mTOR ratios. CONCLUSION: Galangin mitigated cadmium-induced nephrotoxicity thanks to its promising antioxidant, anti-apoptotic, and pro-autophagic effects. In perspective, galangin stimulated the SIRT1/Nrf2/HO-1 and AMPK/mTOR pathways. Hence, it may act as a complementary tool for the management of cadmium-induced renal injury.