Unraveling the hepatic stellate cells mediated mechanisms in aging's influence on liver fibrosis.

Aging enhances numerous processes that compromise homeostasis and pathophysiological processes. Among these, activated HSCs play a pivotal role in advancing liver fibrosis. This research delved into how aging impacts liver fibrosis mechanisms. The study involved 32 albino rats categorized into four groups: Group I (young controls), Group II (young with liver fibrosis), Group III (old controls), and Group IV (old with liver fibrosis). Various parameters including serum ALT, adiponectin, leptin, and cholesterol levels were evaluated. Histopathological analysis was performed, alongside assessments of TGF-ß, FOXP3, and CD133 gene expressions. Markers of fibrosis and apoptosis were the highest in group IV. Adiponectin levels significantly decreased in Group IV compared to all other groups except Group II, while cholesterol levels were significantly higher in liver fibrosis groups than their respective control groups. Group III displayed high hepatic expression of desmin, α-SMA, GFAP and TGF- ß and in contrast to Group I. Increased TGF-ß and FOXP3 gene expressions were observed in Group IV relative to Group II, while CD133 gene expression decreased in Group IV compared to Group II. In conclusion, aging modulates immune responses, impairs regenerative capacities via HSC activation, and influences adipokine and cholesterol levels, elevating the susceptibility to liver fibrosis.

The protective effect of allium cepa against ethylene glycol-induced kidney stones in rats.

1Background: Kidney stones is one of the serious medical conditions affecting populations worldwide. So, we aimed in this study to investigate the protective effect of allium cepa administration against KSD. 2Methods: 24 adult male albino rats were assigned into 3 groups; group I: control group; group II: received ethylene glycol (EG) in the drinking water for 4 weeks; and group III received EG in the drinking water plus freshly prepared allium cepa extract (ACE) for 4 weeks. Renal function tests and urine analysis were done. Tissue oxidative stress markers (SOD and MDA) were assessed, and kidney expression of SIRT-1, Beclin, LC3, osteopontin, and Regucalcin were measured by RT-qPCR. Histopathological assessment and immunohistochemistry for Bax, Beclin-1 and TNF-α were performed. 3Results: There was a significant improved kidney function tests in the ACE received group compared to EG group (P < 0.001). The present study showed less stones formation and apoptosis with decreased osteopontin and autophagy genes expression in the ACE received group compared to EG group (P < 0.001). While, regucalcin and SIRT-1 genes showed higher expression in the former group than the later group (P < 0.001). 4 Conclusion: Alium Cepa extract administration has a significant protective effect against kidney stones formation.

A novel small molecule inhibitor of p38⍺ MAP kinase augments cardiomyocyte cell cycle entry in response to direct cell cycle stimulation.

BACKGROUND AND PURPOSE: Myocardial infarction (MI) is the leading cause of mortality globally due in part to the limited ability of cardiomyocytes (CMs) to regenerate. Recently, we demonstrated that overexpression of four-cell cycle factors, CDK1, CDK4, cyclin B1 and cyclin D1 (4F), induced cell division in ~20% of the post-mitotic CMs overexpressed 4F. The current study aims to identify a small molecule that augments 4F-induced CM cycle induction. EXPERIMENTAL APPROACH, KEY RESULTS: Screening of small molecules with a potential to augment 4F-induced cell-cycle induction in 60-day-old mature human induced pluripotent cardiomyocytes (hiPS-CMs) revealed N-(4,6-Dimethylpyridin-2-yl)-4-(pyridine-4-yl)piperazine-1-carbothioamide (NDPPC), which activates cell cycle progression in 4F-transduced hiPS-CMs. Autodock tool and Autodock vina computational methods showed that NDPPC has a potential interaction with the binding site at the human p38⍺ mitogen-activated protein kinase (p38⍺ MAP kinase), a critical negative regulator of the mammalian cell cycle. A p38 MAP kinase activity assay showed that NDPPC inhibits p38⍺ with 5-10 times lower IC50 compared to the other P38 isoforms in a dose-dependent manner. Overexpression of p38⍺ MAP kinase in CMs inhibited 4F cell cycle induction, and treatment with NDPPC reversed the cell cycle inhibitory effect. CONCLUSION AND IMPLICATIONS: NDPPC is a novel inhibitor for p38 MAP kinase and is a promising drug to augment CM cell cycle response to the 4F. NDPPC could become an adjunct treatment with other cell cycle activators for heart failure treatment.

Protective effect of Salvia hispanica (chia seeds) against obesity induced ovarian disorders in rat model.

The main goal of the current report is to assess the protective impacts of chia seeds against obesity-induced ovarian dysfunctions with a trial to elucidate the mechanism of action. Forty rats were divided into 4 groups including lean untreated, lean consuming chia seeds, obese untreated, and rats consumed high-fat diet (HFD) mixed with ground chia seeds for 10 weeks. Anthropometric measures including visceral fat, peri-ovarian fat, ovarian weights, and duration of the estrous cycle were computed. Serum luteinizing (LH), follicular stimulating (FSH), progesterone, estradiol hormones, and tumor necrosis-α (TNF-α) were estimated. Ovarian histopathology and immunohistochemistry (CD31) were performed. Results showed that chia seeds clearly reduced obesity and induced alteration in anthropometric measures with a clear increase in LH and progesterone. Such seeds notably reversed histopathological alteration and reduced TNF-α, and CD31 induced by HFD. Conclusively, chia seeds have a potential protective role against obesity-induced ovarian dysfunction owing to their anti-inflammatory properties.

Energy Homeostasis-Associated (Enho) mRNA Expression and Energy Homeostasis in the Acute Stress Versus Chronic Unpredictable Mild Stress Rat Models.

The energy homeostasis-associated (Enho) gene, the transcript for the Adropin peptide, is usually linked to energy homeostasis, adiposity, glycemia, and insulin resistance. Studies on Enho expression in stressful conditions are lacking. This work aimed to investigate Enho mRNA expression and energy homeostasis in acute stress (AS) versus chronic unpredictable mild stress (CUMS) rat models. A total of thirty male Wistar rats (180-220 g) were fed a balanced diet with free access to water. Rats were divided into three equal groups (n = 10): (a) the normal control (NC) group; (b) the AS group, where one episode of stress for 2 h was applied; and (c) the CUMS group, in which rats were exposed to a variable program of mild stressors for 4 weeks. Energy homeostasis was analyzed by the PhenoMaster system for the automatic measuring of food intake (FI), respiratory O2 volume (VO2), CO2 volume (VCO2), respiratory quotient (RQ), and total energy expenditure (TEE). Finally, liver, whole brain, and adipose (WAT) tissue samples were collected, total RNA was prepared, and RT-PCR analysis of the Enho gene was performed. The CUMS group showed higher VO2 consumption and VCO2 production, and a higher RQ than the AS group. Furthermore, the TEE and FI were higher in the CUMS group compared to the AS group. Enho gene expression in the liver, brain, and WAT was significantly higher in the CUMS group than in the AS and NC groups. We can conclude that in the chew-fed AS rats, hypophagia was evident, with a shift in the RQ toward fat utilization, with no changes in body weight despite the increase in Enho mRNA expression in all studied tissues. In the CUMS group, the marked rise in Enho mRNA expression may have contributed to weight loss despite increased FI and TEE.

Fractional carbon dioxide laser versus trichloroacetic acid peel in the treatment of pseudo-acanthosis nigricans.

BACKGROUND: Treatment of acanthosis nigricans (AN) is challenging, and new modalities are being explored continuously to increase the therapeutic efficacy. AIM: To evaluate the efficacy and safety of fractional CO2 laser compared to trichloroacetic acid (TCA) peel in the treatment of pseudo-acanthosis nigricans (pseudo-AN). METHODS: The study included 40 patients with pseudo-AN on the neck and axilla allocated into two groups each containing 20 patients. Group (A) was treated with TCA 20% peel applied on the pigmented area while group (B) received fractional CO2 laser. Both treatments were performed till complete clearance or for a maximum of four treatment sessions. Patients with excellent response were further followed up for 6 months after the end of treatment. RESULTS: Both modalities were effective in the treatment of pseudo-AN; however, the therapeutic response was significantly higher in the fractional CO2 laser group compared to the TCA peel group (p < 0.01). Marked to excellent response (51%-100% clearance of AN lesions) was achieved in 85% of the patients in the fractional laser group versus 10% of the patients in the TCA group. Adverse effects, for example, persistent erythema, post-inflammatory hyperpigmentation, and burning sensation, were also statistically higher in the TCA group compared to the laser group (p = 0.04). CONCLUSION: Fractional CO2 laser is a promising effective and well-tolerated treatment modality for pseudo-acanthosis nigricans.

Fractional carbon dioxide laser versus carbon-assisted Q-switched Nd: YAG laser in the treatment of dilated facial pores.

BACKGROUND: The treatment of dilated facial pores is difficult, and the ideal modality is not established yet. Different ablative and nonablative lasers have been used in the treatment of dilated pores with variable outcomes. AIM: To evaluate and compare the efficacy of fractional CO2 laser versus carbon-assisted Q-switched Nd: YAG laser in dilated facial pores. METHODS: The study included 80 patients with dilated pores divided into two groups each containing 40 patients. Group (A) had fractional CO2 laser treatment, and group (B) received Q-switched Nd: YAG laser treatment after the application of a carbon solution on the face. The treatment was repeated monthly for a total of 3 sessions. Objective and subjective assessments of the clinical outcome were performed. RESULTS: Both modalities significantly improved the dilated pores; however, the clinical response was statistically higher and the improvement was maintained for a longer duration of time in the factional laser group compared with the carbon-assisted Q-switched Nd: YAG laser group (p = 0.01). The downtime was significantly lower in the Q-switched Nd: YAG laser group, and the patients' satisfaction rates were comparable in both groups. CONCLUSION: The two laser systems appear to be effective, safe, and well-tolerated in the treatment of dilated pores. The fractional CO2 laser was associated with a significantly higher and more prolonged clinical response.

Cognitive impairment in obese rat model: role of glial cells.

BACKGROUND: Obesity is a worldwide problem. Some studies revealed that it leads to deterioration of the cognitive function, regardless of age. AIM OF THE STUDY: explore the effect of obesity on cognitive function in a rat model of obesity highlighting the role of glial cells. MATERIALS AND METHODS: twenty adult male albino rats were assigned to two groups: group I: consumed normal diet, group II: consumed high-fat diet. Body Mass Index (BMI), serum glucose, insulin, HOMA IR and lipid profile were measured. Also, hippocampal expression of Brain derived neurotrophic factor (Bdnf), synapsin, Ionized calcium binding adaptor molecule 1 (Iba), nuclear factor erythroid -related factor 2 (Nrf2), Myelin basic protein (Mbp) were measured by real-time polymerase chain reaction. The Morris Water Maze is a test used to assess spatial learning and memory capacities of rats. RESULTS: There was a high significant increase in lipid profile, serum glucose, insulin serum levels and HOMA-IR in obese groups with impaired Morris water maze performance compared to control group. There was a significant downregulation in hippocampal Bdnf and synapsin mRNA expression. In addition to decrease in Mbp mRNA expression (P < 0.001). This could be explained by oxidative stress through significant downregulation of Nrf2 mRNA, and inflammation observed in significant upregulation Iba mRNA gene expression in the obese group. CONCLUSION: Many factors contribute to obesity associated cognitive impairment. In our study, we figured out the crucial roles of glial cells including microglial activation and oligodendrocytes affection with other underlying mechanisms including oxidative stress and hippocampal inflammation.

Evaluation of intralesional Candida antigen in diabetic patients with multiple warts.

BACKGROUND: Treatment of warts in diabetic patients with ablative modalities poses a significant risk owing to increased possibility of secondary infection, slow healing, and recurrence. Intralesional immunotherapy has gained popularity in the treatment of warts due to its proven efficacy and good tolerability compared with destructive methods. AIM: To evaluate the intralesional Candida antigen injection for the treatment of multiple warts in diabetic patients. PATIENTS/METHODS: Fifty diabetic patients with multiple genital/nongenital warts were divided into two groups. The first group (30 patients) received intralesional Candida antigen, and the second group (20 patients) had intralesional saline as control. The treatments were injected into the largest wart every 2 weeks until complete clearance of warts or for a maximum of five sessions. RESULTS: Complete clearance of warts was observed in 80% of the diabetic patients in the Candida antigen group compared with 15% in the control group (P < .001). Side effects to Candida antigen included pain during injection in all patients, flu-like symptoms, and localized reaction at the injection site in few patients. CONCLUSION: Intralesional Candida antigen injection can be a promising effective and safe therapeutic option for the treatment of warts in diabetic patients.

Efficacy of topical vs combined oral and topical antifungals in white piedra of the scalp.

BACKGROUND: Topical antifungals are the most commonly used therapy in white piedra of the scalp. However, persistence and relapse of infection still pose a significant challenge. Systemic antifungals have been recommended to enhance the therapeutic response. AIMS: To compare the efficacy of topical antifungal alone versus combined topical and oral antifungals in the treatment of white piedra of the scalp. METHODS: Sixty patients with white piedra of the scalp were divided into 3 groups, each containing 20 patients. Group A received topical clotrimazole, group B received combined topical clotrimazole and oral itraconazole, and group C received combined topical clotrimazole and oral terbinafine. The treatment was continued until clearance of infection was confirmed by dermoscopic and mycological examination. Positive responders were followed up for 3 months after treatment. RESULTS: All the patients achieved complete clearance of infection. The median treatment time in group B was significantly shorter than group A (P < .001) and group C (P < .001), respectively. In addition, the median treatment time in group C was significantly shorter than group A (P = .002). No recurrence of infection was noted during follow-up period. CONCLUSION: The three modalities were effective in the treatment of white piedra of the scalp. The most rapid response was observed with the combined use of topical and oral azoles.