Vol 31, No 21 (2024)

Introduction:Gastrointestinal stromal tumour (GIST) is a common gastrointestinal sarcoma located in the stromal cells of the digestive tract, and molecular studies have revealed the pathogenesis of mutations in KIT and PDGFRA genes. Since imatinib opened the era of targeted therapy for GIST, tyrosine kinase inhibitors (TKIs) that can treat GIST have been developed successively. However, the lack of new drugs with satisfactory therapeutic standards has made addressing resistance a significant challenge for TKIs in the face of the resistance to first-line and second-line drugs. Therefore, we need to find as many drugs and new treatments that block mutated genes as possible.

Methods:We conducted a comprehensive collection of literature using databases, integrated and analysed the selected literature based on keywords and the comprehensive nature of the articles, and finally wrote articles based on the content of the studies.

Results:In this article, we first briefly explained the relationship between GIST and KIT/ PDGFRα and then introduced the related drug treatment. The research progress of TKIs was analyzed according to the resistance of the drugs.

Conclusion:This article describes the research progress of some TKIs and briefly introduces the currently approved TKIs and some drugs under investigation that may have better therapeutic effects, hoping to provide clues to the research of new drugs.

Despite substantial advancements in curative modern medicine in the last few decades, cancer risk and casualty rates have continued to mount globally. The exact reason for cancer's onset and progression is still unknown. However, skeletal and functional abnormalities in the genetic code are assumed to be the primary cause of cancer. Many lines of evidence reported that some medicinal plants can be utilized to curb cancer cell proliferation with a safe, fruitful, and cost-efficient perspective. Curcuminoid, isolated from Curcuma longa, have gotten a lot of focus due to their anticancer potential as they reduce tumor progression, invasion, and dissemination. Further, they modulated signal transduction routes like MAPK, PI3K/Akt/mTOR, JAK/STAT, and Wnt/β-catenin, etc., and triggered apoptosis as well as actuated autophagy in malignant cells without altering the normal cells, thus preventing cancer progression. Besides, Curcuminoid also regulate the function and expression of anti-tumor and carcinogenic miRNAs. Clinical studies also reported the therapeutic effect of Curcuminoid against various cancer through decreasing specific biomarkers like TNF-α, Bcl-2, COX-2, PGE2, VEGF, IκKβ, and various cytokines like IL-12p70, IL-10, IL-2, IFN-γ levels and increasing in p53 and Bax levels. Thus, in the present review, we abridged the modulation of several signal transduction routes by Curcuminoids in various malignancies, and its modulatory role in the initiation of tumor-suppressive miRNAs and suppression of the oncogenic miRNAs are explored. Additionally, various pharmacokinetic approaches have been projected to address the Curcuminoids bioavailability like the use of piperine as an adjuvant; nanotechnology- based Curcuminoids preparations utilizing Curcuminoids analogues are also discussed.

The COVID-19 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) poses a major menace to economic and public health worldwide. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are two host proteins that play an essential function in the entry of SARS-- COV-2 into host cells. Hydrogen sulfide (H2S), a new gasotransmitter, has been shown to protect the lungs from potential damage through its anti-inflammatory, antioxidant, antiviral, and anti-aging effects. It is well known that H2S is crucial in controlling the inflammatory reaction and the pro-inflammatory cytokine storm. Therefore, it has been suggested that some H2S donors may help treat acute lung inflammation. Furthermore, recent research illuminates a number of mechanisms of action that may explain the antiviral properties of H2S. Some early clinical findings indicate a negative correlation between endogenous H2S concentrations and COVID-19 intensity. Therefore, reusing H2S-releasing drugs could represent a curative option for COVID-19 therapy.

Diabetes is one of the lifelong chronic metabolic diseases which is prevalent globally. There is a continuous rise in the number of people suffering from this disease with time. It is characterized by hyperglycemia, which leads to severe damage to the body’s system, such as blood vessels and nerves. Diabetes occurs due to the dysfunction of pancreatic β -cell which leads to the reduction in the production of insulin or body cells unable to use insulin produce efficiently. As per the data shared International diabetes federation (IDF), there are around 415 million affected by this disease worldwide. There are a number of hit targets available that can be focused on treating diabetes. There are many drugs available and still under development for the treatment of type 2 diabetes. Inhibition of gluconeogenesis, lipolysis, fatty acid oxidation, and glucokinase activator is emerging targets for type 2 diabetes treatment. Diabetes management can be supplemented with drug intervention for obesity. The antidiabetic drug sale is the second-largest in the world, trailing only that of cancer. The future of managing diabetes will be guided by research on various novel targets and the development of various therapeutic leads, such as GLP-1 agonists, DPP-IV inhibitors, and SGLT2 inhibitors that have recently completed their different phases of clinical trials. Among these therapeutic targets associated with type 2 diabetes, this review focused on some common therapeutic targets for developing novel drug candidates of the newer generation with better safety and efficacy.

Purpose::The expression level of programmed death ligand-1(PD-L1) in patients with gastric cancer is the key to determining the use of immune drugs. The relationship between PD-L1 expression level and clinical characteristics is worth exploring.

Methods::By setting the search terms correlated to PD-L1 and gastric cancer, a nearly comprehensive search was carried out in four major databases, and the deadline for searching was September 1, 2022. The retrieved documents were further screened by strict inclusion and exclusion criteria after removing the duplication. Next, the quality of the included studies was evaluated with the Newcastle-Ottawa Scale (NOS) scale. Finally, the STATA15.1 software was used to process data and draw plots, and the odds ratios (ORs) were adopted to assess the pooled effect size.

Results::A total of 85 works of literature were included in this study through screening strictly, and detailed data were extracted after evaluating the quality of the literature. The process of analysis was conducted in the whole population, Asia-Africa population, European and American population, and Asian population with CPS≥1, amd all found that the expression of PD-L1 in gastric cancer was correlated with age, tumor size, EBV infection, Her-2 expression and microsatellite status. However, the subgroup of the region also found some differences in Asian and Western regions, which was interesting and worth studying further. The included research of this study did not have significant publish bias.

Conclusion::After careful analysis, this study found that age (>60 years), tumor size (>5cm), EBV infection (+), Her-2 expression (+), microsatellite status (MSI), and mismatch repair status (dMMR) were risk factors for positive expression of PD-L1 in gastric cancer.

Background:Diabetic foot ulcer (DFU) is one of the challenging complications of chronic diabetes.

Objective:The study aimed to investigate whether liothyronine (T3) and liothyronineinsulin (T3/Ins) topical preparations could significantly reduce the healing time of DFU.

Methods:A prospective, randomized, placebo-controlled, patient-blinded clinical trial was conducted on patients with mild to moderate DFU, over a lesion area of no greater than 100 cm2. The patients were randomized to receive T3, T3/Ins, or honey cream 10% as the routine of care twice a day. Patients were examined for tissue healing weekly for 4 weeks, or until the total lesion clearance was observed, whichever was earlier.

Results:Of 147 patients with DFUs, 78 patients (26 per group) completed the study and were included in the final evaluation. At the time of study termination, all participants in each of the T3 or T3/Ins groups were free of symptoms based on the REEDA score, while about 40% of participants in the control group were detected with each of grades 1, 2, or 3. A significant difference was observed on days 7, 14, and 21 of consumption of topical preparations (p-valup < 0.001). The mean time to complete wound closure in the routine care group was about 60.6 days, while it was 15.9 and 16.4 days in T3 and T3/Ins groups, respectively. Within the T3 and T3/Ins groups, significant earlier wound closure was detected at day 28 (p-valup < 0.001).

Conclusion:T3 or T3/Ins topical preparations are effective for wound healing and acceleration of wound closure in mild to moderate DFUs.

Trial Registration:Iranian Registry of Clinical Trials Identifier: IRCT201908100 44500N20, https://www.irct.ir/trial/ 46886, Registration date: 2021-08-22