Rational use of drug

Molecular property prediction is an important task in drug discovery, and with help of self-supervised learning methods, the performance of molecular property prediction could be improved by utilizing large-scale unlabeled dataset. In this paper, we propose a triple generative self-supervised learning method for molecular property prediction, called TGSS. Three encoders including a bi-directional long short-term memory recurrent neural network (BiLSTM), a Transformer, and a graph attention network (GAT) are used in pre-training the model using molecular sequence and graph structure data to extract molecular features...

Pain affects one-third of the global population and is a significant public health issue. The use of opioid drugs, which are the strongest painkillers, is associated with several side effects, such as tolerance, addiction, overdose, and even death. An increasing demand for novel, safer analgesic agents is a driving force for exploring natural sources of bioactive peptides with antinociceptive activity. Since the G protein-coupled receptors (GPCRs) play a crucial role in pain modulation, the discovery of new peptide ligands for GPCRs is a significant challenge for novel drug development...

PURPOSE: Nowadays, it is largely accepted that albumin should not be used in hypoalbuminemia or for nutritional purpose. The most discussed indication of albumin at present is the resuscitation in shock states, especially distributive shocks such as septic shock. The main evidence-based indication is also liver disease. In this review, we provided updated evidence-based instruction for definite and potential indications of albumin administration in clinical practice, with appropriate dosing and duration...

The increasing resistance of clinically relevant microbes against current commercially available antimicrobials underpins the urgent need for alternative and novel treatment strategies. Cationic lipidated oligomers (CLOs) are innovative alternatives to antimicrobial peptides and have reported antimicrobial potential. An understanding of their antimicrobial mechanism of action is required to rationally design future treatment strategies for CLOs, either in monotherapy or synergistic combinations. In the present study, metabolomics was used to investigate the potential metabolic pathways involved in the mechanisms of antibacterial activity of one CLO, C12 -o-(BG-D)-10, which we have previously shown to be effective against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300...

Combining immune checkpoint blockade with chemotherapy through nanotechnology is promising in terms of safety and efficacy. However, the distinct subcellular distribution of each ingredient's action site makes it challenging to acquire an optimal synergism. Herein, a dual-pH responsive hybrid polymeric micelle system, HNP(αPDL16.9 ,Dox5.3 ), is constructed as a proof-of-concept for the spatial cooperativity in chemo-immunotherapy. HNP retains the inherent pH-transition of each polymer, with stepwise disassembly under discrete pH thresholds...

Lactate oxidase (LOX) is a natural enzyme that efficiently consumes lactate. In the presence of oxygen, LOX can catalyse the formation of pyruvate and hydrogen peroxide (H2 O2 ) from lactate. This process led to acidity alleviation, hypoxia, and a further increase in oxidative stress, alleviating the immunosuppressive state of the tumour microenvironment (TME). However, the high cost of LOX preparation and purification, poor stability, and systemic toxicity limited its application in tumour therapy. Therefore, the rational application of drug delivery systems can protect LOX from the organism's environment and maintain its catalytic activity...

The advent of ultra-large libraries of drug-like compounds has significantly broadened the possibilities in structure-based virtual screening, accelerating the discovery and optimization of high-quality lead chemotypes for diverse clinical targets. Compared to traditional high-throughput screening, which is constrained to libraries of approximately one million compounds, the ultra-large virtual screening approach offers substantial advantages in both cost and time efficiency. By expanding the chemical space with compounds synthesized from easily accessible and reproducible reactions and utilizing a large, diverse set of building blocks, we can enhance both the diversity and quality of the discovered lead chemotypes...

The benefits of improved clinical outcomes through blood pressure (BP) reduction have been proven in multiple clinical trials and meta-analyses. The new (2023) guideline from the European Society of Hypertension (ESH) includes β-blockers within five main classes of antihypertensive agents suitable for initiation of antihypertensive pharmacotherapy and for combination with other antihypertensive agents. This is in contrast to the 2018 edition of ESH guidelines that recommended β-blockers for use primarily in patients with compelling indications such as cardiovascular comorbidities, e...

OBJECTIVES: This study aimed to analyze the influence of drug factors on the efficacy of 5-aminolevulinic acid (ALA) photodynamic therapy for oral potentially malignant disorder to improve clinical efficacy and promote clinical rational drug use. METHODS: Literature on the treatment of oral potentially malignant disorder by using ALA photodynamic therapy was collected and analyzed from PubMed, ISI Web of Knowledge database, CNKI, VIP, and Wanfang database. RESULTS: A total of 690 cases were collected, with an average complete response rate of 65...

BACKGROUND/AIM: The global pandemic caused by the novel SARS-CoV-2 virus underscores the urgent need for therapeutic interventions. Targeting the virus's main protease (Mpro), crucial for viral replication, is a promising strategy. OBJECTIVE: The current study aims to discover novel inhibitors of Mpro. METHODS: The current study identified five natural compounds (myrrhanol B (C1), myrrhanone B (C2), catechin (C3), quercetin (C4), and feralolide (C5) with strong inhibitory potential against Mpro through virtual screening and computational methods, predicting their binding efficiencies and validated it using the in-vitro inhibition activity...

1 BACKGROUND: In lung cancer, the use of small-molecule inhibitors, chemotherapy and immunotherapy has led to unprecedented survival benefits in selected patients. Considering most patients will experience a relapse within a short period of time due to single drug resistance, combination therapy is also particularly important to improve patient prognosis. Therefore, more robust biomarkers to predict responses to immunotherapy, targeted therapy, chemotherapy and rationally drug combination therapies may be helpful in clinical treatment choices...

UNLABELLED: Fungal resistance to commonly used medicines is a growing public health threat, and there is a dire need to develop new classes of antifungals. We previously described a peptide produced by Enterococcus faecalis , EntV, that restricts Candida albicans to a benign form rather than having direct fungicidal activity. Moreover, we showed that one 12-amino acid (aa) alpha helix of this peptide retained full activity, with partial activity down to the 10aa alpha helix. Using these peptides as a starting point, the current investigation sought to identify the critical features necessary for antifungal activity and to screen for new variants with enhanced activity using both biofilm and C...

The engineering of novel protein-ligand binding interactions, particularly for complex drug-like molecules, is an unsolved problem which could enable many practical applications of protein biosensors. In this work, we analyzed two engineer ed biosensors, derived from the plant hormone sensor PYR1, to recognize either the agrochemical mandipropamid or the synthetic cannabinoid WIN55,212-2. Using a combination of quantitative deep mutational scanning experiments and molecular dynamics simulations, we demonstrated that mutations at common positions can promote protein-ligand shape complementarity and revealed prominent differences in the electrostatic networks needed to complement diverse ligands...

BACKGROUND: Glaucoma is an optic neuropathy associated with characteristic structural damage to the optic nerve and associated visual dysfunction that may be caused by various pathological processes. A number of pharmacological agents are used to reduce the intraocular pressure (IOP), involving the usage of two or three medications concurrently. Literature is sparse regarding prescription patterns of antiglaucoma drugs, especially regarding variability in public sector vs private sector hospitals...

Multidrug microbial resistance is risking an annual loss of more than 10 million people' lives by 2050. Solutions include the rational use of antibiotics and the use of drugs that reduce resistance or completely obliterate them. Here endophytes come to play due to their high-yield production and inherent nature to produce antimicrobial molecules. Around 40%, 45% and 17% of antibacterial agents were obtained from fungi, actinomycetes, and bacteria, respectively, whose secondary metabolites revealed effectiveness against resistant microbes such as MRSA, MRSE, and Shigella flexneri...

4D (bio-)printing endows 3D printed (bio-)materials with multiple functionalities and dynamic properties. 4D printed materials have been recently used in biomedical engineering for the design and fabrication of biomedical devices, such as stents, occluders, micro-needles, smart 3D-cell engineered micro-environments, drug delivery systems, wound closures, and implantable medical devices. However, the success of 4D printing relies on the rational design of 4D printed objects, the selection of smart materials, and the availability of appropriate types of external (multi-)stimuli...

Drug stability and compatibility are critical factors influencing the cost and logistics of treatment delivery, therapeutic effectiveness, and patient safety. This is particularly significant in the realm of cancer chemotherapeutics, where stability and compatibility studies play a vital role in ensuring rational and safe medicine administration. Oxaliplatin, fluorouracil, and irinotecan, commonly used in various combinations for gastrointestinal cancers, are complemented by co-administration of folinic acid in certain protocols...

The HIV capsid (CA) protein is a promising target for anti-AIDS treatment due to its critical involvement in viral replication. Herein, we utilized the well-documented CA inhibitor PF74 as our lead compound and designed a series of low-molecular-weight phenylalanine derivatives. Among them, compound 7t exhibited remarkable antiviral activity with a high selection index (EC50  = 0.040 µM, SI = 2815), surpassing that of PF74 (EC50  = 0.50 µM, SI = 258)...

INTRODUCTION: Restrictive eligibility criteria in cancer drug trials result in low enrollment rates and limited population diversity. Relaxed eligibility criteria (REC) based on solid evidence is becoming necessary for stakeholders worldwide. However, the absence of high-quality, favorable evidence remains a major challenge. This study presents a protocol to quantitatively evaluate the impact of relaxing eligibility criteria in common non-small cell lung cancer (NSCLC) protocols in China, on the risk-benefit profile...

INTRODUCTION: Bacterial resistance is a major threat to public health worldwide. To gain an understanding of the clinical infection distribution, drug resistance information, and genotype of CRE in Dongguan, China, as well as the resistance of relevant genotypes to CAZ-AVI, this research aims to improve drug resistance monitoring information in Dongguan and provide a reliable basis for the clinical control and treatment of CRE infection. METHODS: VITEK-2 Compact automatic analyzer was utilized to identify 516 strains of CRE collected from January 2017 to June 2023...