Targeting Cytochrome P450 Enzymes in Ovarian Cancers: New Approaches to Tumor-Selective Intervention.

Over the past decade, there have been significant developments in treatment for ovarian cancer, yet the lack of targeted therapy with few side effects still represents a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the tumorigenesis process and metabolism of drugs and has a negative impact on therapy outcomes. Gaining more insight into CYP expression is crucial to understanding the pathophysiology of ovarian cancer since many isoforms are essential to the metabolism of xenobiotics and steroid hormones, which drive the disease's development. To the best of our knowledge, no review articles have documented the intratumoral expression of CYPs and their implications in ovarian cancer. Therefore, the purpose of this review is to provide a clear understanding of differential CYP expression in ovarian cancer and its implications for the prognosis of ovarian cancer patients, together with the effects of CYP polymorphisms on chemotherapy metabolism. Finally, we discuss opportunities to exploit metabolic CYP expression for the development of novel therapeutic methods to treat ovarian cancer.

Globularia arabica Methanolic Leaf Extract Has Higher Efficacy on Burn Wound Healing in Diabetic Rats Compared to Malva slyvestries Methanolic Leaf Extract.

This study aimed to see how effective Globularia arabica and Malva slyvestries-based cream formulations were at healing scald burn wounds in rats. Depending on ointment, preparations of 1%, 5%, and 10% w/w were created. For comparison, an ointment base and a regular burn cream composed soframycine were utilized. Rats introduced a burn by solidifying equipment at 100°C on a 14-mm2 shaved dorsal region. A deep second-degree burn was created, and the percentage of wound contraction was measured over the next 15 days. The rats were euthanized on days 8 and 15, and histological slides were prepared using hematoxylin and eosin staining. Compared to the control group, there was a substantial increase in wound contraction and a significant decrease in the duration of epithelialization in the based ointment-treated groups. However, as paralleled to Globularia arabica, significant (P < .05) results were observed with 10% Globularia arabica cream, whereas Malva slyverstries indicate minimal healing. Soframycine causes a substantial increase in wound contraction (P < .05). Soframycine cream with 10% Globularia arabica therapy resulted in practically complete re-epithelialization and re-structuring of wound tissue on histological examination, whereas Malva slyversries treatment resulted in low epithelization during treatment days. The findings suggest that Globularia arabica-based cream has the wound-healing capability.

Cytochrome 4Z1 Expression Connotes Unfavorable Prognosis in Ovarian Cancers.

Background and Objective: Ovarian cancer is a leading cause of death in females. Since its treatment is challenging and causes severe side effects, novel therapies are urgently needed. One of the potential enzymes implicated in the progression of cancers is Cytochrome 4Z1 (CYP4Z1). Its expression in ovarian cancer remains unknown. Therefore, the current study aims to assess CYP4Z1 expression in different subtypes of ovarian cancers. Materials and Methods: Immunohistochemistry was used to characterize CYP4Z1 expression in 192 cases of ovarian cancers along with eight normal ovarian tissues. The enzyme's association with various clinicopathological characteristics and survival was determined. Results: CYP4Z1 was strongly expressed in 79% of ovarian cancers, compared to negative expression in normal ovarian samples. Importantly, significantly high CYP4Z1 expres-sion was determined in patients with advanced-stage cancer and a high depth of invasion (p < 0.05). Surprisingly, CYP4Z1 expression was significantly associated with a low patient survival rate. Univariate analysis revealed that patient survival was strongly associated with CYP4Z1 expression, tumor stage, depth of invasion, and lymph node metastasis (p < 0.05). Multivariate analysis showed that only CYP4Z1 expression was significantly associated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is correlated with shorter patient survival and has been identified as an independent indicator of a poor prognosis for ovarian cancer patients.

Betaine downregulates microRNA 34a expression via a p53-dependent manner in cisplatin-induced nephrotoxicity in rats.

Cisplatin-induced nephrotoxicity limits its wide application as a chemotherapeutic drug. Betaine is a natural trimethylglycine compound involved in several biological reactions. In this study, the protective effect of betaine against cisplatin-induced nephrotoxicity through modulating the expression of microRNA 34a (miRNA 34a), p53, apoptosis, and inflammation was investigated. Adult Wistar rats were divided into normal group (received vehicle); betaine group (received 250 mg betaine/kg BW/day via oral gavage from Day 1 to Day 25); cisplatin group (received a single intraperitoneal dose of cisplatin at 5 mg/kg BW on Day 21) and betaine + cisplatin group (received the same doses of betaine and cisplatin). The results demonstrated that the cisplatin group exhibited severe kidney tissue damage and an increase in blood creatinine and urea levels. Furthermore, the cisplatin group showed a significant upregulation of miRNA 34a and higher levels of phospho-p53, caspase 3, cytochrome c, NFk B, and IL-1ß compared to the normal group. Remarkably, the betaine + cisplatin group showed significantly decreased blood creatinine and urea concentrations, decreased levels of miRNA 34a, phospho-p53, caspase 3, cytochrome c, NFk B, and IL-1ß as well as improved kidney tissue integrity compared to the cisplatin group. In conclusion, cisplatin-induced nephrotoxicity in rats was associated with upregulation of miRNA 34a expression, apoptosis, and inflammation in p53-dependent manner. These effects were reversed by betaine administration that ultimately improved the kidney function and tissue integrity.

Prevalence of Multi-drug Resistant Acinetobacter baumannii (MDRAB) in Amman Jordan During 2018.

PURPOSE: Acinetobacter baumannii is an opportunistic pathogen, and is among the most problematic nosocomial infections as well as community-acquired infections. This retrospective study was conducted as an attempt to determine the prevalence of multidrug-resistant A. baumannii (MDRAB) isolates from the north and central Jordan area during 2018. METHODS: Patients' records provided by an accredited central private laboratory located in Amman, were examined for A. baumannii isolates identified during this period. The isolates were identified to the species level using the API-10S system and the antimicrobial sensitivity testing was determined using the Kirby-Bauer disc diffusion method. RESULTS: A total of 43 unduplicated isolates were obtained and classified according to clinical sampling source into: Group I (blood), Group II (urine) and Group III (wound, pus, sputum, bedsore and others). Total MDRAB isolates recorded were 29 (67.4 %). Resistance to imipenem was found to be 36% and 94% among groups II and III, respectively, and resistance to meropenem was 60% and 88% among the same groups, respectively. CONCLUSION: Antimicrobial stewardship programs at a national scale are needed to calculate the actual proportion of MDRAB in the country and to combat its increasing emergence and decrease the magnitude of antibiotic resistance.