Folic acid: friend or foe in cancer therapy.

Folic acid plays a crucial role in diverse biological processes, notably cell maturation and proliferation. Here, we performed a literature review using articles listed in electronic databases, such as PubMed, Scopus, MEDLINE, and Google Scholar. In this review article, we describe contradictory data regarding the role of folic acid in cancer development and progression. While some studies have confirmed its beneficial effects in diminishing the risk of various cancers, others have reported a potential carcinogenic effect. The current narrative review elucidates these conflicting data by highlighting the possible molecular mechanisms explaining each point of view. Further multicenter molecular and genetic studies, in addition to human randomized clinical trials, are necessary to provide a more comprehensive understanding of the relationship between folic acid and cancer.

Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy.

Nearly four years after its first appearance, and having gone from pandemic to endemic, the SARS-CoV-2 remains out of control globally. The purpose of this study was to evaluate the clinical efficacy of vitamin D (VD) in COVID-19 and long COVID-19, explain the discrepancy in clinical outcomes and highlight the potential impact of metformin on VD efficacy in recent articles. Articles from January 2022 to August 2023 were selected for this review. The objective of this study was achieved by reviewing, analyzing, and discussing articles demonstrating (1) the mechanism of action of VD (2) observational or randomized clinical trials (RCTs) that support or not the beneficial clinical effects of VD in COVID-19 or long COVID. (3) genetic and non-genetic reasons for the variation in the effects of VD. Articles were collected from electronic databases such as PubMed, Scopus, MEDLINE, Google Scholar, Egyptian Knowledge Bank, Science Direct, and Cochrane Database of Systematic Reviews. Twenty three studies conducted in vitro or in animal models indicated that VD may act in COVID-19 through protecting the respiratory system by antimicrobial peptide cathelicidins, reducing lung inflammation, regulating innate and adaptive immune functions and up regulation of autophagy gene activity. Our review identified 58 clinical studies that met the criteria. The number of publications supporting a beneficial clinical activity of VD in treating COVID-19 was 49 (86%), including 12 meta-analyses. Although the total patients included in all articles was 14,071,273, patients included in publications supporting a beneficial role of VD in COVID-19 were 14,029,411 (99.7%). Collectively, extensive observational studies indicated a decisive relationship between low VD levels and the severity of COVID-19 and mortality outcomes. Importantly, evidence from intervention studies has demonstrated the effectiveness of VD supplements in treating COVID-19. Furthermore, the results of 4 observational studies supported the beneficial role of VD in alleviating symptoms of long COVID-19 disease. However, eight RCTs and one meta-analysis of RCTs may contain low-grade evidence against a beneficial role of VD in COVID-19. Twenty-five articles have addressed the association between VDR and DBP genetic polymorphisms and treatment failure of VD in COVID-19. Impaired VDR signaling may underlie the variability of VD effects as non-genetic mechanisms. Interestingly, in recent studies, metformin has a beneficial therapeutic role in COVID-19 and long COVID-19, possibly by improving AMPK signaling of the VDR and enhancing the efficacy of the VD. In conclusion, evidence has been significantly strengthened over the past 18 months, with several meta-analyses and RCTs reporting conclusive beneficial effects of VD supplementation against COVID-19 and highlighting metformin to improve VDR sensitivity and efficacy in treating COVID-19 and long COVID-19.

Structure-activity relationships andz interindividual variability of drug responses: pharmacogenomics with antimicrobial drugs as a paradigm.

Adverse drug reactions represent a major health burden because they cause notable patient morbidity and mortality. From this viewpoint, several strategies have been developed to prevent or reduce adverse drug reactions. One such strategy is the use of pharmacogenomics. Interindividual variability in drug response and adverse effects is mainly attributable to genetic variation in enzymes such as sulfotransferases and cytochrome P450s. The current narrative review discusses the relationship between the structure and activity of drugs. Specifically, the activity of drugs can be increased and/or their adverse effects can be reduced by altering specific positions in their structures.

Highlights on molecular targets in the management of COVID-19: Possible role of pharmacogenomics.

By the end of 2022, there had been a reduction in new cases and deaths caused by coronavirus disease 2019 (COVID-19). At the same time, new variants of the severe acute respiratory syndrome coronavirus 2 virus were being discovered. Critically ill patients with COVID-19 have been found to have high serum levels of proinflammatory cytokines, especially interleukin (IL)-6. COVID-19-related mortality has been attributed in most cases to the cytokine storm caused by increased levels of inflammatory cytokines. Dexamethasone in low doses and immunomodulators such as IL-6 inhibitors are recommended to overcome the cytokine storm. This current narrative review highlights the place of other therapeutic choices such as proteasome inhibitors, protease inhibitors and nuclear factor kappa B inhibitors in the treatment of patients with COVID-19.

Vitamin D: an essential adjuvant therapeutic agent in breast cancer.

Low serum levels of vitamin D have been reported as a risk factor for breast cancer. This narrative review provides an update on the impact of vitamin D on hormone receptors, notably estrogen receptor subunits, and gives insights on possible therapeutic interventions to overcome breast cancer. In addition, evidence that supports the beneficial use of vitamin D as adjuvant treatment of breast cancer is summarized. Vitamin D deficiency is significantly widespread in patients with triple-negative tumors. Several studies have observed a possible modulatory effect of vitamin D or its analogues on the expression of different hormone receptors in breast cancer and increased sensitivity to tamoxifen. Vitamin D possesses anti-inflammatory and immunomodulatory effects in patients with breast cancer, and the mechanism of action of vitamin D in patients with breast cancer is discussed. In conclusion, vitamin D appears to have a beneficial role in the prevention and management of breast cancer, however, large-scale, randomized controlled trials are needed to confirm the effects of vitamin D in breast cancer prevention or treatment.

A Pilot Study of a Topical Intervention for Treatment of Female Sexual Dysfunction.

PURPOSE/BACKGROUND: Many investigators reported that pharmacological treatment of female sexual dysfunction (FSD) has been a promising field yet to be explored. The purpose of this pilot study was to investigate the efficacy and safety of a topical cream containing small concentrations of three vasodilators with different mechanisms of action in treating FSD. METHODS: In this randomized, controlled pilot trial, premenopausal (n = 30) and postmenopausal (n = 30) cases of 21- to 62-year age range with FSD were allocated randomly into 15 given placebo or 15 given active cream in each group. The women included had FSD for more than a 6-month duration and a total score of Female Sexual Distress Scale-Revised of at least 15. Assessing sexual function by measuring female sexual function index (FSFI) during five clinic visits, one at the end of baseline week and at the end of each week of the 4-week treatment period. The primary end point was changed from baseline FSFI total scores to week 4 treatment. Secondary end point included the changes from baseline arousal, desire, orgasm, and satisfaction scores to week 4 treatment. FINDINGS/RESULTS: The sexual problem reported by patients was orgasmic or/and arousal disorders. In premenopausal cases, active cream led to a high significant increase in mean change FSFI total score from the baseline to week 4 compared with placebo (1.7 ± 1.886 vs 13.35 ± 4.646, respectively; P < 0.0001). Greater improvement of mean change of orgasm and arousal domain score was also observed (0.3 ± 0.45 and 0.35 ± 0.39 vs. 2.66 ± 0.63 and 1.87 ± 0.168, respectively; P < 0.0001). In postmenopausal cases, there were significantly greater improvements with active cream in all sexual functions compared with placebo cream (P < 0.0001). In triple cream, mean change of FSFI total score, orgasm domain score, and arousal score domain were 14.85 ± 6.33, 1.87 ± 0.168 and 2.66 ± 1.182, whereas in the placebo cream, they were 1.54 ± 2.1,0.7 ± 0.76 and 0.22 ± 0.44, respectively. Meanwhile, orgasm scores increased significantly after the use of placebo cream. No serious adverse effects were reported during treatment. IMPLICATIONS/CONCLUSIONS: The results of the pilot trial suggest that topical cream containing small concentrations of three vasodilators may act synergistically, and was effective in improving arousal, orgasmic, and satisfaction disorder with a safer profile for premenopausal and postmenopausal women with FSD. Further studies are recommended to be conducted using a large number of nondepressive and depressive patients.