Targeting vimentin: a multifaceted approach to combatting cancer metastasis and drug resistance.

This comprehensive review explores vimentin as a pivotal therapeutic target in cancer treatment, with a primary focus on mitigating metastasis and overcoming drug resistance. Vimentin, a key player in cancer progression, is intricately involved in processes such as epithelial-to-mesenchymal transition (EMT) and resistance mechanisms to standard cancer therapies. The review delves into diverse vimentin inhibition strategies. Precision tools, including antibodies and nanobodies, selectively neutralize vimentin's pro-tumorigenic effects. DNA and RNA aptamers disrupt vimentin-associated signaling pathways through their adaptable binding properties. Innovative approaches, such as vimentin-targeted vaccines and microRNAs (miRNAs), harness the immune system and post-transcriptional regulation to combat vimentin-expressing cancer cells. By dissecting vimentin inhibition strategies across these categories, this review provides a comprehensive overview of anti-vimentin therapeutics in cancer treatment. It underscores the growing recognition of vimentin as a pivotal therapeutic target in cancer and presents a diverse array of inhibitors, including antibodies, nanobodies, DNA and RNA aptamers, vaccines, and miRNAs. These multifaceted approaches hold substantial promise for tackling metastasis and overcoming drug resistance, collectively presenting new avenues for enhanced cancer therapy.

Fenofibrate-induced renal dysfunction, yes or no?

In the treatment process of hypertriglyceridemia and diabetic nephropathy in type 2 diabetes, fenofibrate (FEN) is a well-known medication. FEN is from fibrate class drugs that using orally; however, as a side effect, it is associated with serum creatinine level increasing. The aim of this review was to determine the real effect of FEN therapy on renal functions based on both experimental and clinical studies. For this review, using the keywords of "fenofibrate" and "renal" and "function," a variety of sources of information banks, including PubMed, Google Scholar, and Scopus, were used, and the published articles were considered and interpreted. Followed by searching in databases, 45 articles were collected. After screening these articles, based on the study source, they were devided into two parts: 23 articles on animal experiments and 22 articles clinical experiments. Based on this information, it seems that the protective mechanism of FEN is related to vascular endothelial functions. The increased creatinine by FEN is related to different sensitivities to FEN effects caused by a polymorphism in different patients. In patients with normal renal function, follow-up of serum creatinine would be necessary after FEN, but the discontinuation of FEN is not recommended. In addition, in diabetic patients with hypertriglyceridemia, FEN treatment would be suggested for protecting the kidney from diabetes-induced renal injury.

CRISPR technology: A versatile tool to model, screen, and reverse drug resistance in cancer.

BACKGROUND: Drug resistance is a serious challenge in cancer treatment that can render chemotherapy a failure. Understanding the mechanisms behind drug resistance and developing novel therapeutic approaches are cardinal steps in overcoming this issue. Clustered regularly interspaced short palindrome repeats (CRISPR) gene-editing technology has proven to be a useful tool to study cancer drug resistance mechanisms and target the responsible genes. In this review, we evaluated original research studies that used the CRISPR tool in three areas related to drug resistance, namely screening resistance-related genes, generating modified models of resistant cells and animals, and removing resistance by genetic manipulation. We reported the targeted genes, study models, and drug groups in these studies. In addition to discussing different applications of CRISPR technology in cancer drug resistance, we analyzed drug resistance mechanisms and provided examples of CRISPR's role in studying them. Although CRISPR is a powerful tool for examining drug resistance and sensitizing resistant cells to chemotherapy, more studies are required to overcome its disadvantages, such as off-target effects, immunotoxicity, and inefficient delivery of CRISPR/cas9 into the cells.

The circadian rhythm: an influential soundtrack in the diabetes story.

Type 2 Diabetes Mellitus (T2DM) has been the main category of metabolic diseases in recent years due to changes in lifestyle and environmental conditions such as diet and physical activity. On the other hand, the circadian rhythm is one of the most significant biological pathways in humans and other mammals, which is affected by light, sleep, and human activity. However, this cycle is controlled via complicated cellular pathways with feedback loops. It is widely known that changes in the circadian rhythm can alter some metabolic pathways of body cells and could affect the treatment process, particularly for metabolic diseases like T2DM. The aim of this study is to explore the importance of the circadian rhythm in the occurrence of T2DM via reviewing the metabolic pathways involved, their relationship with the circadian rhythm from two perspectives, lifestyle and molecular pathways, and their effect on T2DM pathophysiology. These impacts have been demonstrated in a variety of studies and led to the development of approaches such as time-restricted feeding, chronotherapy (time-specific therapies), and circadian molecule stabilizers.

Efficacy of adjunctive topical liposomal clarithromycin on systemic Glucantime in Old World cutaneous leishmaniasis: a pilot clinical study.

Aim: This study aimed to investigate the effects of topical liposomal clarithromycin in combination with meglumine antimoniate (Glucantime®) on cutaneous leishmaniasis (CL) lesions. Methods: This pilot, randomized, double-blinded clinical trial was conducted on patients with CL lesions. Patients were randomly assigned to two groups: the first group received liposomal clarithromycin in combination with Glucantime for 28 days, while the second group received Glucantime and a placebo. Afterward, patients were followed up at 1.5, 3, and 6 months after treatment initiation and were evaluated for recovery time, induration, and size of the lesions. Results: Sixty patients with CL lesions were divided into two separate groups with 30 members each and were examined. Within-group analysis revealed that recovery time in the clarithromycin group was 26.65 ± 5.12 days, while in the placebo group, it was 32.84 ± 24.43, which was statistically insignificant (p = 0.18). Lesion size comparison in the first and last follow-ups reduced in both groups: 7.73 ± 4.31 to 0.48 ± 0.50 in the clarithromycin group (p = 0.006) and 5.47 ± 5.83 to 0.76 ± 0.88 in the placebo group (p = 0.03). Moreover, the size of lesions in the intervention group was significantly reduced compared to that in the placebo group (p = 0.02). Recognizable induration reduction was observed in the clarithromycin group (2.60 ± 0.77 to 1.0 ± 0.00). No adverse effects attributable to clarithromycin were reported. Conclusion: The administration of liposomal clarithromycin in combination with systemic Glucantime had a significant beneficial effect on reducing lesion size in leishmaniasis. Further studies on larger populations are recommended. Systematic Review Registration: https://www.irct.ir/trial/46611.

Circadian and Immunity Cycle Talk in Cancer Destination: From Biological Aspects to In Silico Analysis.

Cancer is the leading cause of death and a major problem to increasing life expectancy worldwide. In recent years, various approaches such as surgery, chemotherapy, radiation, targeted therapies, and the newest pillar, immunotherapy, have been developed to treat cancer. Among key factors impacting the effectiveness of treatment, the administration of drugs based on the circadian rhythm in a person and within individuals can significantly elevate drug efficacy, reduce adverse effects, and prevent drug resistance. Circadian clocks also affect various physiological processes such as the sleep cycle, body temperature cycle, digestive and cardiovascular processes, and endocrine and immune systems. In recent years, to achieve precision patterns for drug administration using computational methods, the interaction of the effects of drugs and their cellular pathways has been considered more seriously. Integrated data-derived pathological images and genomics, transcriptomics, and proteomics analyses have provided an understanding of the molecular basis of cancer and dramatically revealed interactions between circadian and immunity cycles. Here, we describe crosstalk between the circadian cycle signaling pathway and immunity cycle in cancer and discuss how tumor microenvironment affects the influence on treatment process based on individuals' genetic differences. Moreover, we highlight recent advances in computational modeling that pave the way for personalized immune chronotherapy.

Effect of Adjunctive Topical Liposomal Azithromycin on Systemic Azithromycin on Old World Cutaneous Leishmaniasis: A Pilot Clinical Study.

The treatment of Cutaneous Leishmaniasis (CL) is complex, and the search for safer, more efficient, and cost-effective treatments is ongoing. This study aimed to evaluate the efficacy of the combination of liposomal and oral azithromycin as the first clinical study against CL. This assessor-blind, randomized clinical trial was conducted in out-patients Leishmaniasis clinic of Skin Diseases and Leishmaniasis. The cutaneous lesions of eligible participants were randomized to receive either oral azithromycin or the combined oral and topical liposomal azithromycin. All participants received 250 mg of azithromycin twice daily or 8 mg/per kg for 4 weeks. In the combination group, a topical liposomal formulation of 0.04 mmol/mL of azithromycin was administered as 0.2-0.5 cc twice daily according to the lesion size in order to make a thin layer of the drug on the surface of the lesion. The size and induration changes from baseline to the end of the study were analyzed. Twenty-one lesions of 13 patients in the combination group and 20 lesions of 14 patients in the oral group were recruited. The mean ± SD of improvement was significantly different between two groups after 12 weeks (3.89 ± 0.46 vs. 3.15 ± 1.23 P = 0.02 combination group vs. oral group respectively). The patients did not experience any systemic adverse effects related to azithromycin and the only adverse effects related to topical treatment were mild pruritus in 2 cases. In conclusion, the combination of oral and topical liposomal formulation of azithromycin is safe and effective to treat CL.

Protein kinase inhibitors' classification using K-Nearest neighbor algorithm.

Protein kinases are enzymes acting as a source of phosphate through ATP to regulate protein biological activities by phosphorylating groups of specific amino acids. For that reason, inhibiting protein kinases with an active small molecule plays a significant role in cancer treatment. To achieve this aim, computational drug design, especially QSAR model, is one of the best economical approaches to reduce time and save in costs. In this respect, active inhibitors are attempted to be distinguished from inactive ones using hybrid QSAR model. Therefore, genetic algorithm and K-Nearest Neighbor method were suggested as a dimensional reduction and classification model, respectively. Finally, to evaluate the proposed model's performance, support vector machine and Naïve Bayesian algorithm were examined. The outputs of the proposed model demonstrated significant superiority to other QSAR models.

Rituximab associated necrosis: A case report.

BACKGROUND: Rituximab is a B-cell-depleting unconjugated monoclonal IgG1 antibody that targets the transmembrane protein CD20. This article reports on a case with the rare complication known as Rituximab-associated mucosal necrosis. CASE PRESENTATION: The present case report addresses, for the first time, a patient affected by Devic's syndrome presenting with oral manifestations of palatal necrosis after rituximab treatment. CONCLUSION: The present case raises the possibility of anti-CD20 antibody contributing to the development of palatal mucosal necrosis in some patients. Given the increasing administration of rituximab as a result of its efficacy against several diseases, a report on the potential iatrogenic effects of this drug is essential.