Genetic and neural mechanisms that inhibit Drosophila from mating with other species.

Genetically hard-wired neural mechanisms must enforce behavioral reproductive isolation because interspecies courtship is rare even in sexually naïve animals of most species. We find that the chemoreceptor Gr32a inhibits male D. melanogaster from courting diverse fruit fly species. Gr32a recognizes nonvolatile aversive cues present on these reproductively dead-end targets, and activity of Gr32a neurons is necessary and sufficient to inhibit interspecies courtship. Male-specific Fruitless (Fru(M)), a master regulator of courtship, also inhibits interspecies courtship. Gr32a and Fru(M) are not coexpressed, but Fru(M) neurons contact Gr32a neurons, suggesting that these genes influence a shared neural circuit that inhibits interspecies courtship. Gr32a and Fru(M) also suppress within-species intermale courtship, but we show that distinct mechanisms preclude sexual displays toward conspecific males and other species. Although this chemosensory pathway does not inhibit interspecies mating in D. melanogaster females, similar mechanisms appear to inhibit this behavior in many other male drosophilids.

Modular genetic control of sexually dimorphic behaviors.

Sex hormones such as estrogen and testosterone are essential for sexually dimorphic behaviors in vertebrates. However, the hormone-activated molecular mechanisms that control the development and function of the underlying neural circuits remain poorly defined. We have identified numerous sexually dimorphic gene expression patterns in the adult mouse hypothalamus and amygdala. We find that adult sex hormones regulate these expression patterns in a sex-specific, regionally restricted manner, suggesting that these genes regulate sex typical behaviors. Indeed, we find that mice with targeted disruptions of each of four of these genes (Brs3, Cckar, Irs4, Sytl4) exhibit extremely specific deficits in sex specific behaviors, with single genes controlling the pattern or extent of male sexual behavior, male aggression, maternal behavior, or female sexual behavior. Taken together, our findings demonstrate that various components of sexually dimorphic behaviors are governed by separable genetic programs.

Bone marrow-derived mesenchymal stem cells reduce CCl4-induced kidney injury and fibrosis in male Wistar rats.

AIM: This study explores the possible therapeutic role of rats and mice bone marrow-derived mesenchymal stem cells (BM-MSCs) on renal damage and toxicity brought on by carbon tetrachloride (CCl4) in Wistar rats. METHODS: Following an intraperitoneal injection of CCl4 (0.5 mL/kg b.w. twice weekly) for eight weeks, male Wistar rats were intravenously treated with rats and mice BM-MSCs (1 × 106 cells in 0.2 mL Dulbecco's Modified Eagle Medium (DMEM)/rat/week) a week for four weeks. Kidney functions were evaluated and kidney samples were examined using hematoxylin and eosin (H&E), Masson's trichrome (MT) staining techniques, and electron microscopy analysis. Kidney cyclooxygenase-2 (COX-2), protein 53 (p53), and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical staining techniques. Additionally, bioindicators of oxidative stress and antioxidant defense systems were identified in kidney tissue. RESULTS: In CCl4-injected rats, serum creatinine, urea, and uric acid levels significantly increased, as did renal lipid peroxidation (LPO), while superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH) transferase, and GSH levels significantly dropped in the kidneys. Histologically, the kidneys displayed a wide range of structural abnormalities, such as glomerular shrinkage, tubular dilations, inflammatory leukocytic infiltration, fibroblast proliferation, and elevated collagen content. Inflammatory cytokines like COX-2 and TNF-α as well as the pro-apoptotic mediator p53 were considerably upregulated. Treatment of BM-MSCs from mice and rats with CCl4-injected rats considerably reduced the previously noted abnormalities. CONCLUSIONS: By boosting antioxidant defense and reducing apoptosis and inflammation, BM-MSCs from mice and rats were able to enhance kidney function and histological integrity in rats that had received CCl4 injections.

The anticarcinogenic effect of eugenol on lung cancer induced by diethylnitrosamine/2-acetylaminofluorene in Wistar rats: insight on the mechanisms of action.

This study was designed to assess the ameliorative effects of eugenol and to propose the possible mechanisms of action of eugenol in diethylnitrosamine (DENA)/acetylaminofluorene (AAF)-caused lung cancer in Wistar rats. To induce lung cancer, DENA at a dose of 150 mg/kg body weight (b.wt) for 2 weeks were intraperitoneally injected once each week and AAF was administered orally at a dose of 20 mg/kg b.wt. four times each week for the next 3 weeks. DENA/AAF-administered rats were orally supplemented with eugenol at a dose of 20 mg/kg b.wt administered once a day until 17 weeks starting from the 1st week of DENA administration. Lung histological lesions, including sheets of tumor cells, micropapillary adenocarcinoma, and apoptotic cells, resulting from the DENA/AAF dosage, were ameliorated by eugenol treatment. However, a significant drop in the levels of LPO in the lungs and a remarkable rise in GSH content and GPx and SOD activities were observed in DENA/AAF-administered rats treated with eugenol compared with those in DENA/AAF-administered controls. Moreover, in DENA/AAF-administered rats, eugenol supplementation significantly reduced TNF-α and IL-1ß levels and mRNA expression levels of NF-κB, NF-κB p65, and MCP-1 but significantly elevated the level of Nrf2. Furthermore, the DENA/AAF-administered rats treated with eugenol exhibited a significant downregulation of Bcl-2 expression levels in addition to a significant upregulation in P53 and Bax expression levels. Otherwise, the administration of DENA/AAF elevated the protein expression level of Ki-67, and this elevation was reversed by eugenol treatment. In conclusion, eugenol has effective antioxidant, anti-inflammatory, proapoptotic, and antiproliferative properties against lung cancer.

Ameliorative Effect of Curcumin Nanoparticles against Monosodium Iodoacetate-Induced Knee Osteoarthritis in Rats.

Aim: This study is aimed at evaluating the use of curcumin-loaded polylactic-co-glycolic acid nanoparticles (CUR-loaded PLGA NPs) as a treatment against monosodium iodoacetate- (MIA-) induced knee OA. Materials and Methods: Eighteen rats were assigned to three groups (n = 6), namely, normal control group that received intra-articular injections (IAIs) of saline, an OA control group that received an IAIs of MIA (2 mg/50 µL), and a treatment group (MIA+CUR-loaded PLGA NPs) that received IAIs of CUR-loaded PLGA NPs (200 mg/kg b.wt). Results: The CUR NP treatment against knee OA alleviated radiographic alternations and histopathological changes and inhibited the upregulation in the serum levels of interleukin-1ß, tumor necrosis factor-α, interleukin-6, and transforming growth factor-beta and the downregulation in interleukin-10. CUR NP-treated joints also decreased the mRNA expression of nuclear factor-kappa B and inducible nitric oxide synthase and the protein expression of matrix metalloproteinase-13 and caspase-3. Finally, CUR-loaded PLGA NP treatment mitigated the loss of type II collagen, which resulted in a significant reduction in malondialdehyde level and increased the glutathione content and superoxide dismutase activity compared with that of the OA group. Conclusion: This study demonstrated that the administration of CUR NPs could provide effective protection against MIA-induced OA and knee joint histological deteriorated changes due to its anti-inflammatory, antioxidant, and antiapoptotic properties.

Quercetin and naringenin abate diethylnitrosamine/acetylaminofluorene-induced hepatocarcinogenesis in Wistar rats: the roles of oxidative stress, inflammation and cell apoptosis.

This study was designed to assess the preventive effects and to suggest the probable mechanisms of action of quercetin and naringein in diethylnitrosamine (DEN)/2-acetylaminofluorene (2AAF)-induced hepatocarcinogenesis in Wistar male rats. The chemical-induction of hepatocarcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg body weight (b.w.) twice/week for two weeks, followed by oral administration of 2AAF at 20 mg/kg body weight (b.w.) 4 times/week for 3 weeks. The DEN/2AAF-administered rats were co-treated with quercetin and naringenin at dose level of 10 mg/kg b. w. by oral gavage for 20 weeks. The treatment of DEN/2AAF-administered rats with quercetin and naringenin significantly prevented the elevations in serum levels of liver function indicators (ALT, AST, ALP, γ-GT, total bilirubin and albumin) and liver tumor biomarkers including AFP, CEA and CA19.9. The cancerous histological lesions and inflammatory cells infiltration in liver of DEN/2AAF-administered rats were remarkably suppressed by treatments with quercetin and naringenin. The hepatic oxidative stress markers including NO level and lipid peroxidation significantly decreased while the SOD, GPx and CAT activities and GSH content significantly increased in DEN/2AAF-administered rats treated with quercetin and naringenin when compared to DEN/2AFF-administered control rats. Furthermore, the lowered mRNA expression of liver IL-4, P53 and Bcl-2 in of DEN/2AAF-administered rats were significantly counteracted by treatment with quercetin and naringenin. Taken together, our results demonstrate that quercetin and naringenin may abate hepatocarcinogenesis via enhancement of anti-inflammatory, anti-oxidant and apoptotic actions.

Optimizing preclinical learning with retrieval practice: A call to action.

This Personal View is about our experience with preclinical education as medical students. We discuss the problem with current medical education in light of an ever-growing body of medical knowledge and increasing student disengagement with preclinical lectures. We briefly review the concept of retrieval practice as an effective, evidence-based learning strategy that helped us retain knowledge for longer periods and propose that medical educators should adopt this strategy to best prepare medical students to navigate the vastly expanding scope of modern medicine.

Simultaneous Orbital and Intracranial Abscesses in 17 Cases.

PURPOSE: To describe the demographics, clinical presentation, treatment, and outcomes of a rare cohort with simultaneous orbital and intracranial abscesses. METHODS: A historical cohort study of 17 patients with simultaneous orbital and intracranial abscesses between 2010 and 2018 was performed. The demographics, location of abscesses, treatment, and outcomes of these patients were analyzed. RESULTS: The mean age was 26.9 years (range 5-83 years). Fourteen patients (82%) were male. In this cohort, the most common orbital abscess location was the superior orbit, involved in 14 patients (82%). The most common site of intracranial abscess was the frontal lobe, involved in 16 patients (94%). Concurrent sinus disease was present in 16 patients (94%). Surgical evacuation was the standard of treatment, with 94% of patients undergoing at least one surgical procedure. Streptococcus species were the most common, isolated from 6 sinus cultures (43%), 3 orbitotomy cultures (21%), and 4 craniectomy cultures (36%). Staphylococcus species were also common. Most patients (94%) had stable or improved mental status and visual function at the conclusion of their treatment. CONCLUSIONS: Simultaneous orbital and intracranial abscesses are rare. Local invasion from the orbit into the intracranial space may occur from direct spread, thus superior orbital abscesses pose the greatest risk for intracranial spread. Additional factors such as infection with Streptococcus and Staphylococcus species as well as male sex appear to be risk factors for intracranial spread. For those who develop intracranial abscesses, young age and absence of seizures or altered mental status at presentation may be associated with favorable outcomes.

Bee Venom: From Venom to Drug.

Insects of the order Hymenoptera have a defensive substance that contains many biologically active compounds. Specifically, venom from honeybees (Apis mellifera) contains many enzymes and peptides that are effective against various diseases. Different research papers stated the possibility of using bee venom (a direct bee sting or in an injectable form) in treating several complications; either in vivo or in vitro. Other reports used the active fractions of bee venom clinically or at labratory scale. Many reports and publications have stated that bee venom and its constituents have multiple biological activities including anti-microbial, anti-protozoan, anti-cancer, anti-inflammatory, and anti-arthritic properties. The present review aims to refer to the use of bee venom itself or its fractions in treating several diseases and counteracting drug toxicities as an alternative protocol of therapy. The updated molecular mechanisms of actions of bee venom and its components are discussed in light of the previous updated publications. The review also summarizes the potential of venom loaded on nanoparticles as a drug delivery vehicle and its molecular mechanisms. Finally, the products of bee venom available in markets are also demonstrated.

Epidemiology, outcomes, and prognostic factors of orbital lymphoma in the United States.

PURPOSE: We performed an epidemiological study of orbital lymphoma in the United States to determine how histological subtypes confer differing prognosis, and understand other factors associated with survival. METHODS: All patients in the Surveillance, Epidemiology and End Results database diagnosed with a histologically confirmed orbital lymphoma between 1973 and 2014 were included. Exclusion criteria included diagnosis at autopsy and the presence of other malignancies. Measures included patient demographic information, histological subtype and treatment modalities. Outcomes included overall and disease specific survival. RESULTS: Of the 1504 cases identified, 702 were male (46.7%, mean age: 64.4 years, standard deviation [SD]: 15.3) and 802 were female (53.3%, mean age: 67.5 years, SD: 14.3). Mucosal associated lymphoid tissue (MALT) (49.5%) and diffuse large B cell lymphoma (DLBCL) (19.5%) were the two most common histologic subtypes. MALT lymphoma conferred the best prognosis (10-year cancer specific survival [CSS] 90.2%, 95% Confidence Interval [CI] 87.4% - 93.1%) and DLBCL conferred the worst prognosis (10-year CSS 68.6%, 95% CI 62.5% - 75.3%) (p < .001, log-rank test). Older age (Hazard Ratio [HR]: 3.71, 95% Confidence Interval [CI]: 2.94-4.66, p < .001), male sex (HR: 1.22, 95% CI: 1.039-1.441, p = .015), no radiation (HR: 1.72, 95% CI: 1.46-2.02, p < .001) and DLBCL histology were significant predictors of worse overall survival. CONCLUSIONS: DLBCL histology confers the worst outcomes whereas MALT lymphoma confers the best outcome in orbital lymphoma. Age, gender, and radiation treatment also influence survival. These epidemiological results can be used clinically to communicate outcomes on the basis of patient characteristics and disease histology.

New Antiproliferative Cembrane Diterpenes from the Red Sea Sarcophyton Species.

The combination of liquid chromatography coupled to high resolution mass spectrometry (LC-HRESMS)-based dereplication and antiproliferative activity-guided fractionation was applied on the Red Sea-derived soft coral Sarcophyton sp. This approach facilitated the isolation of five new cembrane-type diterpenoids (1-5), along with two known analogs (6 and 7), as well as the identification of 19 further, known compounds. The chemical structures of the new compounds were elucidated while using comprehensive spectroscopic analyses, including one-dimensional (1D) and two-dimensional (2D) NMR and HRMS. All of the isolated cembranoids (1-7) showed moderate in vitro antiproliferative activity against a human breast cancer cell line (MCF-7), with IC50 ranging from 22.39-27.12 µg/mL. This class of compounds could thus serve as scaffold for the future design of anticancer leads.

Reversible structural and functional changes after intraocular pressure reduction in patients with glaucoma.

PURPOSE: The aim of this study was to evaluate structural and functional improvement following intraocular pressure (IOP) reduction in patients with glaucoma using Spectral Domain Optical Coherence Tomography (SD-OCT), Visual Field (VF) testing, and Visual Evoked Potentials (VEP). METHODS: A total of 76 eyes from 61 patients underwent SD-OCT, VF and VEP testing. Sixty-two eyes were put in either an acutely high (group 1, IOP > 32 mmHg) or mildly high (group 2, IOP between 22 and 31 mmHg) IOP group and underwent a pressure-lowering intervention. Fourteen eyes with stable glaucoma were controls (group 3, IOP < 22 mmHg). SD-OCT, VF and VEP testing were subsequently performed on all patients at three follow-up visits. Results from these follow-up periods were analyzed for signs of functional and structural improvement. RESULTS: Both group 1 and group 2 patients demonstrated significant decrease in the average cup to disc ratio (p < 0.05) following the intervention. Post-interventional reduction of cup volume was also significant for group 2 patients (p < 0.05). RNFL thickness changes were insignificant. Qualitative grading of VFs by two observers showed improvement in group 1 patients' VFs (p = 0.021). VEP measurements were mostly insignificant, with the exception of High Contrast Latency (LHC) deteriorating for group 2 patients in the first follow-up visit (p = 0.025). CONCLUSIONS: This study provides evidence for structural disc cupping reversal following IOP lowering interventions. These changes were not related to the amount of pressure lowering. While there was evidence of functional improvement as measured by VF testing, VEP was unable to detect any reversible changes.

Up-regulation of Hsp72 and keratin16 mediates wound healing in streptozotocin diabetic rats.

BACKGROUND: Impaired wound healing is a complication of diabetes and a serious problem in clinical practice. We previously found that whey protein (WP) was able to regulate wound healing normally in streptozotocin (STZ)-diabetic models. This subsequent study was designed to assess the effect of WP on heat shock protein-72 (Hsp72) and keratin16 (Krt16) expression during wound healing in diabetic rats. METHODS: WP at a dosage of 100 mg/kg of body weight was orally administered daily to wounded normal and STZ-diabetic rats for 8 days. RESULTS: At day 4, the WP-treated diabetic wound was significantly reduced compared to that in the corresponding control. Diabetic wounded rats developed severe inflammatory infiltration and moderate capillary dilatation and regeneration. Treated rats had mild necrotic formation, moderate infiltration, moderate to severe capillary dilatation and regeneration, in addition to moderate epidermal formation. Hsp72 and Krt16 densities showed low and dense activity in diabetic wounded and diabetic wounded treated groups, respectively. At day 8, WP-treatment of diabetic wounded animals revealed great amelioration with complete recovery and closure of the wound. Reactivity of Hsp72 and Krt16 was reversed, showing dense and low, or medium and low, activity in the diabetic wounded and diabetic wounded treated groups, respectively. Hsp72 expression in the pancreas was found to show dense reactivity with WP-treated diabetic wound rats. CONCLUSION: This data provides evidence for the potential impact of WP in the up-regulation of Hsp72 and Krt16 in T1D, resulting in an improved wound healing process in diabetic models.

Ovicidal, larvicidal and adulticidal activity of black pepper (Piper nigrum L.) essential oil and tea tree oil (Melaleuca alternifolia) against Haemonchus contortus.

Haemonchosis is a worldwide helminthic disease affecting ruminants. The anthelminthic resistance has become raised. Medicinal plants are safely used as synthetic anthelmintics. Currently, the efficacy of black pepper essential oil (BPO) and tea tree oil (TTO) were in vitro evaluated against Haemonchus contortus adults, eggs and larvae at concentrations of 1.25, 2.5 and 5 mg/ml in addition to the commercially used albendazole at a concentration of 10 µg/ml. Oils were used in both normal and nanoparticles-loaded forms. Oxidative stress enzymes of worms were estimated. Scanning electron microscopy (SEM) for treated worms was done. Both normal and nanoemulsion forms of both BPO and TTO stopped the adult motility [BPO 2.5 h (hrs), NBPO 1.5 h, TTO 3 h, NTTO 1.5 h] and induced a marked decrease in the oviposition. Post treatment, the egg development and hatching were significantly (P ≤ 0.05) reduced. The damage of the egg shell, embryonal cessation and destruction of larvae occurred. Noticeable elevated antioxidant enzymes (catalase CAT, glutathione transferase GST and glutathione GSH) were found, while oxidative enzymes (lipid peroxidation LPO and nitric oxide synthase NOS) decreased. Scanning electron microscopy (SEM) for both oil-treated worms revealed anterior ends damage and several cuts associated with cuticular pores. The use of albendazole induced more or less anthelmintic and enzymatic activities with less morphological alterations of adults revealed by SEM. This study proved the marked anthelmintic potency of the BPO and TTO and their nanoemulsion forms against H. contortus rather than the widely used anthelmintic drugs.

Limiting prolonged inflammation during proliferation and remodeling phases of wound healing in streptozotocin-induced diabetic rats supplemented with camel undenatured whey protein.

BACKGROUND: Impaired diabetic wound healing occurs as a consequence of excessive reactive oxygen species (ROS) and inflammatory cytokine production. We previously found that whey protein (WP) was able to normally regulate the ROS and inflammatory cytokines during the inflammatory phase (first day) in streptozotocin (STZ)-diabetic wound healing. This study was designed to assess the effect of WP on metabolic status, the inflammation and anti-inflammation response, oxidative stress and the antioxidant defense system during different phases of the wound healing process in diabetic rats. WP at a dosage of 100 mg/kg of body weight, dissolved in 1% CMC, was orally administered daily to wounded normal (non-diabetic) and STZ-induced diabetic rats for 8 days starting from the 1st day after wounding. RESULTS: The data revealed that WP enhanced wound closure and was associated with an increase in serum insulin levels in diabetic rats and an alleviation of hyperglycemic and hyperlipidemic states in diabetic animals. The increase in insulin levels as a result of WP administration is associated with a marked multiplication of ß-cells in the core of islets of Langerhans. WP induced a reduction in serum TNF-α, IL-1ß and IL-6 levels and an increase in IL-10 levels, especially on the 4th day after wounding and treatment. WP also suppressed hepatic lipid peroxidation and stimulated the antioxidant defense system by increasing the level of glutathione and the activity of glutathione-S-transferase, glutathione peroxidase and superoxide dismutase (SOD) in wounded diabetic rats. CONCLUSIONS: WP was observed to enhance wound closure by improving the diabetic condition, limiting prolonged inflammation, suppressing oxidative stress and elevating the antioxidant defense system in diabetic rats.

Transcriptional profiling of Drosophila male-specific P1 (pC1) neurons.

In Drosophila melanogaster, the P1 (pC1) cluster of male-specific neurons both integrates sensory cues and drives or modulates behavioral programs such as courtship, in addition to contributing to a social arousal state. The behavioral function of these neurons is linked to the genes they express, which underpin their capacity for synaptic signaling, neuromodulation, and physiology. Yet, P1 (pC1) neurons have not been fully characterized at the transcriptome level. Moreover, it is unknown how the molecular landscape of P1 (pC1) neurons acutely changes after flies engage in social behaviors, where baseline P1 (pC1) neural activity is expected to increase. To address these two gaps, we use single cell-type RNA sequencing to profile and compare the transcriptomes of P1 (pC1) neurons harvested from socially paired versus solitary male flies. Compared to control transcriptome datasets, we find that P1 (pC1) neurons are enriched in 2,665 genes, including those encoding receptors, neuropeptides, and cell-adhesion molecules (dprs/DIPs). Furthermore, courtship is characterized by changes in ~300 genes, including those previously implicated in regulating behavior (e.g. DopEcR, Octß3R, Fife, kairos, rad). Finally, we identify a suite of genes that link conspecific courtship with the innate immune system. Together, these data serve as a molecular map for future studies of an important set of higher-order and sexually-dimorphic neurons.

Omentin roles in physiology and pathophysiology: an up-to-date comprehensive review.

Omentin (intelectin) was first detected in the visceral omental adipose tissue. It has mainly two isoforms, omentin-1 and -2, with isoform-1 being the main form in human blood. It possesses insulin-sensitizing, anti-inflammatory, anti-atherogenic, cardio-protective, and oxidative stress-decreasing effects. Omentin's cardiovascular protective actions are caused by the improved endothelial cell survival and function, increased endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability, enhanced vascular smooth muscle cells (VSMCs) relaxation with reduced proliferation, decreased inflammation, and suppressed oxidative stress. Omentin may also have a potential role in different cancer types and rheumatic diseases. Thus, omentin is an excellent therapeutic target in many diseases, including diabetes mellitus (DM), metabolic syndrome (MetS), cardiovascular diseases (CVDs), inflammatory diseases, and cancer. This review demonstrates the physiological functions of omentin in ameliorating insulin resistance (IR), vascular function, and inflammation and its possible share in managing obesity-linked diseases, such as metabolic disorders, DM, and cardiovascular conditions.

Naringin and naringenin counteract taxol-induced liver injury in Wistar rats via suppression of oxidative stress, apoptosis and inflammation.

This research aimed to evaluate the preventing effects of naringin, naringenin, and their combination on liver injury induced by Taxol (paclitaxel) in Wistar rats. Male Wistar rats received 2 mg/kg Taxol intraperitoneal injections twice weekly on the second and fifth days of each week for 6 weeks. During the same period as Taxol administration, rats were given naringin, naringenin, or a combination of the two (10 mg/kg b.wt) every other day. Treatment with naringin and/or naringenin reduced the abnormally high serum levels of total bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma-glutamyl transferase in Taxol-treated rats. It also significantly increased the level of serum albumin, indicating an improvement in the liver. The perturbed histological liver changes were markedly improved due to the naringin and/or naringenin treatment in Taxol-administered rats. Additionally, the treatments reduced high hepatic lipid peroxidation and increased liver glutathione content as well as the activities of superoxide dismutase and glutathione peroxidase. Furthermore, the treatments reduced the levels of alpha-fetoprotein and caspase-3, a pro-apoptotic mediator. The naringin and naringenin mixture appeared more effective in improving organ function and structural integrity. In conclusion, naringin and naringenin are suggested to employ their hepatoprotective benefits via boosting the body's antioxidant defense system, reducing inflammation, and suppressing apoptosis.

Mesenchymal Stem Cells and Begacestat Mitigate Amyloid-ß 25-35-Induced Cognitive Decline in Rat Dams and Hippocampal Deteriorations in Offspring.

Alzheimer's disease (AD) is the most common cause of age-related neurodegeneration and cognitive decline. AD more commonly occurs in females than in males, so it is necessary to consider new treatments specifically targeting this population. The present study investigated the protective effects of Begacestat (γ-secretase inhibitor-953, GSI-953) and bone marrow-derived mesenchymal stem cells (BM-MSCs) during pregnancy on cognitive impairment in rat dams and neurodegeneration in offspring caused by the intracerebroventricular injection of Aß 25-35 before pregnancy. The performances of dams injected with amyloid-ß 25-35 (Aß 25-35) during behavioral tests were significantly impaired. The offspring of Aß 25-35-injected dams treated with BM-MSCs or GSI-953 showed a dramatically reduced number and size of activated microglial cells, enhancement in the processes length, and a decrease in the proinflammatory cytokine levels. Additionally, BM-MSC or GSI-953 therapy reduced Aß 25-35-induced increases in tau phosphorylation and amyloid precursor protein levels in the neonates' hippocampus and elevated the lower levels of glycogen synthase kinase-3 and brain-derived neurotrophic factor; moreover, reversed Aß 25-35-induced alterations in gene expression in the neonatal hippocampus. Finally, the treatments with BM-MSC or GSI-953 are globally beneficial against Aß 25-35-induced brain alterations, particularly by suppressing neural inflammation, inhibiting microglial cell activation, restoring developmental plasticity, and increasing neurotrophic signaling.

Computational and Molecular Docking Studies of New Benzene Sulfonamide Drugs with Anticancer and Antioxidant Effects.

BACKGROUND: The studies on the potential usage of benzene sulfonamide derivatives as anticancer agents are limited. benzene sulfonamide derivatives are currently used as anticancer agents against different breast cancer cell lines, such as MCF-7, lung cancer cells (A549), prostate cancer cells (Du-145), and cervical cells (HeLa). OBJECTIVE: A series of new sulfonamide drugs are synthesized by reacting aldehydes thio-semi-carbazones derivatives with benzene sulphonyl chloride to form benzylidene-N-(phenylsulfonyl) hydrazine-1-carbothioamide derivatives. Studying the anticancer effects against MCF-7 breast carcinoma cell lines and the antioxidant activities of these newly synthesized compounds. METHODS: Studying the anticancer effects against MCF-7 breast carcinoma cell lines and the antioxidant activities of these newly synthesized compounds. To study the anti-breast cancer activity of the newly synthesized compounds, a molecular docking study is used to analyze the binding energy for the nonbonding interactions between the ligands (studied compounds) and receptor (4PYP (pdb code: 4FA2)) against human breast cancer (MCF-7) cells. The bioavailability of all studied compounds is confirmed by pharmacological investigations using Mol inspiration and absorption, distribution, metabolism, excretion, and toxicity online servers. RESULTS: The two derivatives, 2-(4- methoxy benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4c) and 2-(4-dimethylamino) benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4e) show the most potent anticancer effects against MCF-7 breast carcinoma cell lines. Meanwhile, these two derivatives show the lowest antioxidant activities. CONCLUSION: The different spectral techniques were used to confirm the structure of the novel synthesized compounds. Further, 2-(4-(dimethyl amino) benzylidene)-N- (phenylsulfonyl)hydrazine-1-carbothioamide (4e) and 2-(4- methoxy benzylidene)-N-(phenylsulfonyl) hydrazine-1 carbothioamide (4c) were the most potent anticancer derivatives against MCF-7 breast carcinoma cell lines. Furthermore, they exhibited the most potent antioxidant activities. Meanwhile, the 2-benzylidene-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4a) and 2-(4-chloro benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4d) had the lowest antioxidant potentials. The estimated binding energies, inhibition constant, intermolecular energies, and reference RMSD produced from docking for all studied compounds were reported. These values showed that all studied compounds formed stable complexes with the receptor with high binding affinity. It was further noted from the ADMET analysis that compounds 4c, 4d, and 4e have good absorption, low toxicity in the human liver, and medium BBB penetration. Hence, these studied compounds (4c-4e) may be suggested as potential compounds against human breast cancer MCF-7 cells.