Hypertension (HP) is a health condition that overloads the heart and increases the risk of heart attack and stroke. In an infarction, the lack of oxygen causes an exclusive use of glycolysis, which becomes a crucial source of ATP for the heart with a higher glucose uptake mediated by glucose transporters (GLUTs). Due to the unpleasant effects of antihypertensives, new drugs need to be researched to treat this disease. This study aimed to evaluate the cardioprotective effect of three novel antihypertensive compounds (LQMs, \"Laboratorio de Química Medicinal\") synthesized from Changrolin under hypoxic conditions with the participation of two primary cardiac GLUT1 and GLUT4 using a high-salt diet HP model. The model used a diet with 10% salt to increase arterial blood pressure in Wistar rats. In isolated cardiomyocytes from these rats, glucose uptake was measured during hypoxia, evaluating the participation of GLUTs with or without the animals\' previous treatment with LQM312, 319, and 345 compounds. In silico calculations were performed to understand the affinity of the compounds for the trafficking of GLUTs. Results: Control cells do shift to glucose uptake exclusively in hypoxia (from 1.84 ± 0.09 µg/g/h to 2.67 ± 0.1 µg/g/h). Meanwhile, HP does not change its glucose uptake (from 2.38 ± 0.24 µg/g/h to 2.33 ± 0.26 µg/g/h), which is associated with cardiomyocyte damage. The new compounds lowered the systolic blood pressure (from 149 to 120 mmHg), but only LQM312 and LQM319 improved the metabolic state of hypoxic cardiomyocytes mediated by GLUT1 and GLUT4. In silico studies suggested that Captopril and LQM312 may mimic the interaction with the AMPK γ-subunit. Therefore, these compounds could activate AMPK, promoting the GLUT4 trafficking signaling pathway. These compounds are proposed to be cardioprotective during hypoxia under HP.

RET fusions are relatively rare in Non-Small-Cell Lung Cancers (NSCLCs), being around 1-2% of all NSCLCs. They share the same clinical features as the other fusion-driven NSCLC patients, as follows: younger age, adenocarcinoma histology, low exposure to tobacco, and high risk of spreading to the brain. Chemotherapy and immunotherapy have a low impact on the prognosis of these patients. Multitargeted RET inhibitors have shown modest activity jeopardized by high toxicity. New potent and selective RET inhibitors (RET-Is) (pralsetinib and selpercatinib) have achieved a higher efficacy minimizing the known toxicities of the multitargeted agents. This review will describe the sensitivity of immune-checkpoint inhibitors (ICIs) in RET fusion + NSCLC patients, as well their experiences with the \'old\' multi-targeted RET inhibitors. This review will focus on the advent of new potent and selective RET-Is. We will describe their efficacy as well as the main mechanisms of resistance to them. We will further proceed to deal with the new drugs and strategies proposed to overcome the resistance to RET-Is. In the last section, we will also focus on the safety profile of RET-Is, dealing with the main toxicities as well as the rare but severe adverse events.

Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide. Skin exposure is the leading risk factor for initiating NMSC. Ultraviolet (UV) light induces various genomic aberrations in both tumor-promoting and tumor-suppressing genes in epidermal cells. In conjunction with interactions with a changed stromal microenvironment and local immune suppression, these aberrations contribute to the occurrence and expansion of cancerous lesions. Surgical excision is still the most common treatment for these lesions; however, locally advanced or metastatic disease significantly increases the chances of morbidity or death. In recent years, numerous pharmacological targets were found through extensive research on the pathogenic mechanisms of NMSCs, leading to the development of novel treatments including Hedgehog pathway inhibitors for advanced and metastatic basal cell carcinoma (BCC) and PD-1/PD-L1 inhibitors for locally advanced cutaneous squamous cell carcinoma (cSCC) and Merkel cell carcinoma (MCC). Despite the efficacy of these new drugs, drug resistance and tolerability issues often arise with long-term treatment. Ongoing studies aim to identify alternative strategies with reduced adverse effects and increased tolerability. This review summarizes the current and emerging therapies used to treat NMSC.

BACKGROUND: Toxoplasmosis is a worldwide distributed zoonosis caused by Toxo-plasma gondii (T. gondii), an obligate intracellular protozoan. The infection in immunocompetent hosts usually progresses with mild or no symptoms. However, in immunocompromised individu-als, this disease can cause severe or fatal symptoms.
METHODS: Sulfadiazine and pyrimethamine are two drugs used as standard therapies for human toxoplasmosis. Although they do not cause chronic infection, they may cause hematological tox-icity, hypersensitivity, intolerance, teratogenic effects, gastrointestinal disorders, and bone mar-row suppression.
RESULTS: The limited effect, significant toxicity, and emerging resistance to current drugs available to treat T. gondii infections require investigating other effective, nontoxic, and well-tolerated al-ternatives. Medicinal plants are, traditionally, the most promising sources used to treat infectious diseases.
CONCLUSIONS: This review provides data on new therapeutic and prophylactic methods for T. gondii infection based on the use of extracts and/or compounds derived from natural products, which have been reported to be useful as alternative treatment options in the last 20 years.

暂无摘要。

Drugs have structural homology across similar biological targets. Small molecule drugs have the efficacy to target specific molecular targets within the cancer cells with enhanced cell membrane permeability, oral administration, selectivity, and specific affinity. The objective of this review is to highlight the clinical importance and synthetic routes of new small molecule oncology drugs approved by the FDA during the period 2021-2022. These marketed drugs are listed based on the month and year of approval in chronological order. We believed that an in-depth insight into the synthetic approaches for the construction of these chemical entities would enhance the ability to develop new drugs more efficiently.

BACKGROUND: Integrated Stress Response Inhibitor (ISRIB) works by inhibiting the integrated stress response, a cellular pathway involved in the regulation of protein synthesis during stress conditions. Conditions that have been studied or suggested as potential candidates for treatment with ISRIB include neurological and metabolic disorders, cognitive impairment, viral infections, and cancer.
OBJECTIVE: The study aimed to discuss the challenges related to specificity, long-term safety, and disease-specific considerations crucial for realizing the full potential of ISRIB.
METHODS: A narrative review of the literature has been conducted to delve into ISRIB\'s chemistry, mechanisms of action, disease-specific considerations, and long-term safety implications.
RESULTS: While ISRIB has shown promising results in preclinical studies, more research is needed to determine its safety and effectiveness in human patients. Clinical trials are required to validate its therapeutic potential for various conditions. Despite having been proposed a decade ago, news of its clinical trials has been circulated only recently, without any published information yet and with rumors that its efficacy vs. safety profile may be compromised by side effects.
CONCLUSIONS: While ISRIB offers exciting prospects for a range of biomedical applications, addressing challenges related to specificity, disease-specific considerations, and importantly long-term safety, is crucial for realizing its full potential.

UNASSIGNED: The goal of this activity is to educate pharmacists about the use of idarucizumab for the reversal of dabigatran anticoagulant activity.
UNASSIGNED: At the completion of this activity, the reader will be able to:1.Describe the pharmacology and pharmacokinetics of idarucizumab.2.Discuss the risks associated with the use of idarucizumab.3.Discuss the potential benefit of idarucizumab for an individual patient.4.Apply the information on the use of idarucizumab to a case study.

Liver fibrosis is a key step in the developmental process of various chronic liver diseases, including cirrhosis. Therefore, the focus and difficulty of liver disease research have always been on how to reverse liver fibrosis. However, due to complex mechanisms, difficulties in endpoint evaluation, a lack of non-invasive diagnostic methods, and other factors, the research and development of new drugs are hindered and lengthy. Currently, some new drugs are being researched and developed, which signifies the prospect is optimistic.
肝纤维化是各种慢性肝病向肝硬化发展过程中的关键步骤，如何能通过药物逆转肝纤维化始终为肝病领域研究的重点和难点。然而，由于机制复杂、终点评估困难、缺少无创诊断方法等因素，一些新的药物正在研发中，肝纤维化新药研发道阻且长，但前景乐观。.

Liver disease is a serious public health problem worldwide, affecting human health. However, there are still many unmet needs for the treatment of liver disease, especially with new therapeutic drugs. At present, there is no treatment method to eradicate the hepatitis B virus, nor are there therapeutic drugs for liver fibrosis, liver failure, and others. Chemotherapy and targeted immunotherapy are still unsatisfactory for liver cancer. This article provides an overview of the current status and challenges that arise in new drug research and development for liver diseases.
肝病在全球是一个严重的公共卫生问题，影响人类的健康，但是目前针对肝病治疗，尤其是新药治疗仍有许多未满足的需求。目前尚无根除乙型肝炎病毒的治疗方法，也无肝纤维化和肝衰竭等的治疗药物，肝癌的化疗和靶向及免疫治疗还不尽如人意。现就目前针对肝病的新药研发的现状与面临的挑战进行概述。.