Effectiveness Of Drugs Research Articles

Rare bleeding disorders: Advances in management

Inherited factor coagulation deficiencies and vascular bleeding disorders, associated with bleeding of various severity, are often classified as rare bleeding disorders (RBDs). These include inherited fibrinogen disorders, inherited platelet function disorders (IPFD) and hereditary haemorrhagic telangiectasia (HHT). In the last decades, there have been large increases in knowledge on the epidemiology, genetics, physiopathology, clinical features, and diagnosis of RBDs, but improvements in management have been more limited and remain challenging. The treatment mainstay of RBDs is based only on replacement of a few available coagulation factor concentrates or cryoprecipitates. There is growing interest in therapeutic agents that enhance coagulation or inhibiting anticoagulant pathways in RBDs. In severe IPFD, the optimal platelet transfusion strategy is not yet established. Moreover, data is scarce on the effectiveness and safety of desmopressin and/or antifibrinolytic drugs often used for milder IPFD treatment. The best fibrinogen replacement strategy (prophylaxis vs. on demand) in afibrinogenemia is still debated. Similarly, the optimal trough fibrinogen target level for treatment of acute bleeding, and the role of fibrinogen replacement during pregnancy in mild hypofibrinogenemia and dysfibrinogenemia, have not been properly evaluated. The therapeutic arsenal in HHT includes antifibrinolytics and a series of antiangiogenic agents whose potential efficacy has been tested in small studies or are under investigation for treatment of bleeding. However, there is need to address several issues, including the optimal dosing strategies, the potential emergent toxicity of longer-term use, and the impact of systemic antiangiogenic treatment on visceral arteriovenous malformations.

Effects of Six Natural Compounds and Their Derivatives on the Control of Coccidiosis in Chickens.

Chicken coccidiosis costs the poultry industry over GBP 10 billion per year. The main method of preventing and controlling coccidiosis in chickens continues to be the use of drugs. Unfortunately, the prevalence of drug resistance in the field reduces or even eliminates the effectiveness of drugs, and drug residues in the food supply chain can also can be harmful to humans. Therefore, safe and effective anticoccidial drugs are urgently needed. Natural products have many advantages such as being safe, effective and inexpensive and are a sustainable way to control coccidiosis. In this study, the anticoccidial effects of six natural compounds were tested by Eimeria tenella infection. Oocyst production, cecum lesion, body weight gain, feed conversion ratio, and intestinal microbiota were measured. The results showed that nerolidol had a moderate effect on maintaining both body weight gain and feed conversion ratio. Silymarin and dihydroartemisinin showed significant anticoccidial effects by reducing total oocyst output. Dihydroartemisinin also significantly reduced the cecum lesion caused by Eimeria infection, but this compound may be toxic to the host at such informed doses because it decreases growth and survival rates. In addition, both silymarin and dihydroartemisinin partly restored the microbiota after challenge. This indicates that silymarin, dihydroartemisinin, and nerolidol are effective in the control of chicken coccidiosis. Our data provide basic knowledge about the anticoccidial effects of such natural compounds/derivates.

Study of utilisation pattern and adverse reaction monitoring of drugs used for relief of musculoskeletal pain in a tertiary care teaching hospital in Eastern Odisha

Musculoskeletal conditions are the most common cause of long-term pain and physical disability. The burden of musculoskeletal conditions is not only in terms of global numbers but also in terms of physical and psychosocial disability. Pain arising from musculoskeletal conditions of the major joints like back, neck, shoulder, knee or multi-site involvement results in diminished quality of life. Evidence for the effectiveness and safety of the various drugs used to alleviate MSP is uncertain.The present study was an observational, cross-sectional study which included patients with complaints of musculoskeletal pain attending Regional Spine Injury Centre, S.C.B Medical College and Hospital. A total of 100 patients were included in the study. Demographic data of all the patients was collected and their level of significance in the causation of musculoskeletal pain was assessed. The prescription pattern of the drugs for musculoskeletal pain was analysed. All the patients taking the drugs were monitored for any adverse drug reaction and the same was documented.Low back ache (28%) was the most common type of musculoskeletal pain observed. Aceclofenac was the most common analgesic prescribed, followed by paracetamol and etoricoxib. Aceclofenac and paracetamol was the most common combination used. Pain abdomen was the most common ADR encountered.

Estimation of cancer cell migration in biomimetic random/oriented collagen fiber microenvironments

Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment, playing a crucial role in pathological processes such as tumor invasion and metastasis. However, conventional two-dimensional cell culture and animal models have limitations in studying the influence of tumor microenvironment on cancer cell migration. Fortunately, the further development of microfluidic technology has provided solutions for the study of such questions. We utilize microfluidic chip to build a random collagen fiber microenvironment (RFM) model and an oriented collagen fiber microenvironment (OFM) model that resemble early stage and late stage breast cancer microenvironments, respectively. By combining cell culture, biochemical concentration gradient construction, and microscopic imaging techniques, we investigate the impact of different collagen fiber biochemical microenvironments on the migration of breast cancer MDA-MB-231-RFP cells. The results show that MDA-MB-231-RFP cells migrate further in the OFM model compared to the RFM model, with significant differences observed. Furthermore, we establish concentration gradients of the anticancer drug paclitaxel in both the RFM and OFM models and find that paclitaxel significantly inhibits the migration of MDA-MB-231-RFP cells in the RFM model, with stronger inhibition on the high concentration side compared to the low concentration side. However, the inhibitory effect of paclitaxel on the migration of MDA-MB-231-RFP cells in the OFM model is weak. These findings suggest that the oriented collagen fiber microenvironment resembling the late-stage tumor microenvironment is more favorable for cancer cell migration and that the effectiveness of anticancer drugs is diminished. The RFM and OFM models constructed in this study not only provide a platform for studying the mechanism of cancer development, but also serve as a tool for the initial measurement of drug screening.

Comparative Effectiveness of Antidiabetic Drugs as an Additional Therapy to Metformin in Women with Polycystic Ovary Syndrome: A Systematic Review of Metabolic Approaches.

Metformin is commonly prescribed to treat polycystic ovary syndrome (PCOS) patients, but in some cases, it may not be effective even at high doses or may cause intolerable side effects. Therefore, recent studies have examined the impact of combining metformin with other antidiabetic medications. A systematic search was performed in Scopus, PubMed, Web of Science, and Embase up to 30 June 2023. All interventional studies that assessed the efficacy of different antidiabetic agents were included. Among the 3488 records found in the primary search, 16 papers were included. Our study showed that dipeptidyl peptidase-4 inhibitors (DPP4i) had the most significant impact on glycemic profile, while thiazolidinediones (TZDs) had the most influence on lipid levels. However, it was observed that patients taking only metformin experienced a greater increase in high-density lipoprotein cholesterol (HDL-C) levels. Glucagon-like peptide-1 receptor agonists (GLP1RAs) effectively modified various anthropometric measurements, such as weight, body mass index, waist circumference, and waist-to-hip ratio. The effects of different antidiabetic drugs on hormone levels were inconclusive, although testosterone levels were more affected by GLP1RA, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and TZDs. None of the combined therapies showed a significant change in blood pressure. Since PCOS is a metabolic disorder, choosing the best combination of antidiabetic drugs in the clinical course of PCOS patients will be very important. Today, it seems that we need a new metabolic approach for better treatment of the metabolic aspects of these patients.

The efficacy and safety of novel antiepileptic drugs in treatment of epilepsy of patients with brain tumors.

This meta-analysis aimed to assess the effectiveness and safety of novel antiepileptic drugs (AEDs) in treating epilepsy in patients with brain tumors (BTRE). A search was conducted on PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to February 2023, with English language restriction. In this meta-analysis, 18 clinical trials involving 755 BTRE patients were included to assess the efficacy and safety of novel AEDs in BTRE treatment. At the last follow-up, a ≥50% reduction in seizure frequency was experienced by 72% of patients (random-effects model, 95% CI = 0.64-0.78) using novel AEDs. At the last follow-up, seizure freedom was experienced by 34% of patients (random-effects model, 95% CI = 0.28-0.41) using novel AEDs. The pooled incidence of AEs was found to be 19% (95% CI: 13%-26%), with a withdrawal rate due to adverse effects of only 3%. Comparable efficacy and incidence of adverse effects were observed between lacosamide and perampanel. This meta-analysis suggests that novel antiepileptic drugs are deemed effective for seizure control in brain tumor patients, particularly when used as adjunctive therapy. Although lacosamide and perampanel received more focus in studies, no significant difference was observed in the efficacy and adverse reactions of these two drugs in seizure control. Further randomized controlled trials are deemed necessary to validate our findings.

Antiviral Drugs for Treatment of Human Monkeypox: A Systematic Review/Meta-analysis

Background. On 23 July 2022, the World Health Organization declared a Public Health Emergency of International Concern. Monkeypox is a zoonotic viral disease caused by the monkeypox virus that is transmitted from animals to humans or from human to human. To date, treatment for human monkeypox is mostly symptomatic, as there is no specific standard antiviral treatment. Persons with severe symptoms and signs, immunocompromised patients, children younger than 8 years, and pregnant individuals should be considered for specific antiviral treatment. Objective. This study aims to assess effectiveness of antiviral drugs in treatment of human monkeypox. Methodology. Published clinical trials and cohort studies on the role of antivirals in the management of human monkeypox that were identified through a comprehensive search of electronic databases up to April 1, 2023. The patients included were children and adults confirmed with monkeypox. The diagnosis was based on PCR or clinical symptoms. The intervention was antivirals administration in human monkeypox patients, versus supportive treatment/placebo. Outcome measured include the duration of monkeypox until recovery, need for hospitalization, and ICU admission. Results. We included four completed studies with 195 participants assessing the safety, pharmacokinetics, and efficacy of antiviral treatments for human monkeypox compared to placebo. Three studies investigated Tecovirimat (st-246), and one investigated Brincidofovir. Both drugs were safe, tolerable, and effective with no serious adverse effects. The other 5 studies were not completed and are ongoing. Conclusion. There are currently no approved antivirals for the treatment of monkeypox; some medications could be authorized for outbreak use and are now under investigation, such as Tecovirimat, Cidofovir, and Brincidofovir.

Expression of circulating long non-coding MALAT1 and GAS5 under metformin treatment in type 2 diabetic patients

The most prevalent metabolic disorder is type 2 diabetes. Long non-coding RNAs are one of the most effective factors in disease pathogenesis and are also promising therapeutic targets. GAS5 and MALAT1 are two lncRNAs that participate in glucose homeostasis. This study aims to compare the expression levels of lncRNA-GAS5 and lncRNA-MALAT1 in the PBMCs of T2DM patients with healthy individuals. A total of 60 diabetic patients and 60 healthy individuals were selected, including an equal number of males and females. The two groups of diabetic patients—those who had been taking metformin and those who hadn't—were further divided into two subgroups based on their BMI. Following PBMC RNA extraction, cDNA synthesis and the Real-Time qPCR method were used to assess the relative gene expression. Some diabetes risk factors, including elevated FBP, triglycerides, and WBC, and reduced AST enzyme, were observed in Iranian T2DM patients. Additionally, diabetic patients have lower levels of GAS5 and MALAT1 gene expression; nevertheless, T2DM patients' MALAT1 expression decreased in response to metformin treatment. However, increasing in BMI, can be elevated MALAT1 and GAS5 expression in normal individuals. Our study reveals that GAS5 and MALAT1 gene expression is reduced in T2DM patients, and their expression is also related to BMI. Furthermore, it is suggested to consider the effectiveness of new diabetes drugs based on the simulation of the expression pattern of pivotal long non-coding RNAs in the pathways involved in blood sugar regulation.

Implications of Immunogenicity Testing for Therapeutic Monoclonal Antibodies: A Quantitative Pharmacology Framework

The interpretation of immunogenicity results for a mAb product and prediction of its clinical consequences remain difficult, despite enormous advances in methodologies and efforts toward the best practice for consistent data generation and reporting. To this end, the contribution from the clinical pharmacology discipline has been largely limited to comparing descriptively the pharmacokinetic (PK) profiles by antidrug antibodies (ADA) status or testing the significance of ADA as a covariate in a population PK setting, similar to the practice for small-molecule drugs in investigating the effect of an intrinsic/extrinsic factor on the drug disposition. There is a need for a mAb disposition framework that captures the dynamics of ADA formation and drug’s interactions with the ADA and target as parts of the drug distribution and elimination. Here we describe such a framework and examine it against the PK, ADA, and clinical response data from a phase 3 trial in patients treated with adalimumab. The proposed framework offered a generalized understanding of how the dose, target affinity, and drug/ADA analyte forms affects the manifestation of ADA response with regard to its detections and alterations of drug disposition and effectiveness. Furthermore, as an example, its utility for dose considerations was demonstrated through predicting for late-stage trials of a PCSK9 inhibitor in terms of development in ADA incidence and titers, and consequences on the drug disposition, interaction with target, and downstream lowering effect on LDL-C.Graphical

Effectiveness and safety of the combination drug "Femo-Klim" evaluated in patients with former cancer and moderate menopausal disorders

Aim: to assess effectiveness and safety of a combination phytoestrogen-based product “Femo-Klim” in treatment of moderate climacteric disorders in gynecological cancer patients.

Experience with interleukin-23 inhibitor guselkumab using in patients with severe psoriasis and the impact of the disease on the psycho-emotional background

Psoriasis is a chronic immune-mediated disease that leads not only to damage to the skin and its appendages, but is also associated with concomitant systemic diseases, including damage to the musculoskeletal system, cardiovascular pathologies, kidney disease, metabolic syndrome and changes in the nervous system. Not long ago, a term was introduced to unite psoriasis and concomitant comorbid diseases – psoriatic disease. Recently, special attention has been paid to assessing the psychoemotional state and quality of life of patients with psoriasis who bear the burden of a chronic disease. It is no secret that any skin disease significantly worsens the quality and standard of life of the patient and can lead to social and professional stigma and discrimination, and a number of restrictions. Psoriatic disease is recognized as a multisystem inflammatory disease and a holistic approach to treatment is recommended, focusing on comorbidities, including mental health, psychosocial well-being and quality of life. The Dermatological Life Quality Index (DLQI) is one of the most convenient indices that allows you to assess the severity of the burden of chronic skin diseases, including psoriasis, on a person’s daily activities; a correlation was found between the severity of psoriasis, the presence of concomitant diseases, especially psoriatic arthritis and the DLQI level. DLQI is higher in patients with moderate to severe psoriasis, in patients with mild psoriasis (low PASI index), but with damage to socially significant areas of the skin (face, hands and feet, scalp, genitals, nail plates), in patients with active manifestations of psoriatic disease in the form of concomitant diseases, which complicates the choice of drug for treatment. The availability, effectiveness, and treatment regimens of modern drugs play an important role in the psycho-emotional state of patients. Today the biological drugs have been actively used in the treatment of psoriasis, which have a number of advantages compared to drugs of basic anti-inflammatory therapy and phototherapy, and, accordingly, are more effective and are of value for patients who experience emotional discomfort from a chronic skin disease in everyday life. The purpose of this article was to study the prevalence and nature of mental and psychiatric pathologies in patients with psoriasis, the possible improvement of DLQI in patients with psoriasis using a biological drug from the group of interleukin-23 inhibitors guselkumab.

Pancreatic Cancer Treatment Targeting the HGF/c-MET Pathway: The MEK Inhibitor Trametinib.

Pancreatic cancer is characterized by fibrosis/desmoplasia in the tumor microenvironment, which is primarily mediated by pancreatic stellate cells and cancer-associated fibroblasts. HGF/c-MET signaling, which is instrumental in embryonic development and wound healing, is also implicated for its mitogenic and motogenic properties. In pancreatic cancer, this pathway, along with its downstream signaling pathways, is associated with disease progression, prognosis, metastasis, chemoresistance, and other tumor-related factors. Other features of the microenvironment in pancreatic cancer with the HGF/c-MET pathway include hypoxia, angiogenesis, metastasis, and the urokinase plasminogen activator positive feed-forward loop. All these attributes critically influence the initiation, progression, and metastasis of pancreatic cancer. Therefore, targeting the HGF/c-MET signaling pathway appears promising for the development of innovative drugs for pancreatic cancer treatment. One of the primary downstream effects of c-MET activation is the MAPK/ERK (Ras, Ras/Raf/MEK/ERK) signaling cascade, and MEK (Mitogen-activated protein kinase kinase) inhibitors have demonstrated therapeutic value in RAS-mutant melanoma and lung cancer. Trametinib is a selective MEK1 and MEK2 inhibitor, and it has evolved as a pivotal therapeutic agent targeting the MAPK/ERK pathway in various malignancies, including BRAF-mutated melanoma, non-small cell lung cancer and thyroid cancer. The drug's effectiveness increases when combined with agents like BRAF inhibitors. However, resistance remains a challenge, necessitating ongoing research to counteract the resistance mechanisms. This review offers an in-depth exploration of the HGF/c-MET signaling pathway, trametinib's mechanism, clinical applications, combination strategies, and future directions in the context of pancreatic cancer.

ОПЫТ ЛЕЧЕНИЯ ПОСЛЕРОДОВОГО ЭНДОМЕТРИТА У КОРОВ

The purpose of the study is to conduct a comparative analysis of the therapeutic effectiveness of a local antiseptic drug based on tea tree essential oil for acute postpartum catarrhal endometritis in cows. The study was conducted at the Department of VNB, Obstetrics and Physiology of Farm Animals of the Krasnoyarsk State Agrarian University, on the basis of the dairy farm of the Balakhta District of the Krasnoyarsk Region. The object of the study is red-motley cows. Research methods: obstetric and gynecological medical examination of breeding stock; the diagnosis of acute postpartum catarrhal-purulent endometritis was established during a clinical and gynecological examination of fresh cows, which inclu-ded thermometry, rectal and vaginal examination. The diagnosis was considered confirmed when pathological discharge of a catarrhal nature appeared from the uterus during rectal massage. Two experimental groups of fresh cows were formed according to the principle of analogues (based on live weight, age, lactation, clinical manifestation of the form of acute endometritis). In the 1st experimental group, scheme № 1 was used: a 25 % oil solution of tea tree essential oil was administered intrauterinely in a dose of 20 ml daily once a day until clinical recovery; eleovit 8 ml was administered intramuscularly on the 1st and 5th days of treatment; uteroton 10 ml was administered intramuscularly daily once a day for 3 days; 0.05 % chlorhexidine solution 200 ml – intravaginally; rectal massage of the uterus once a day. In the 2nd experimental group, treatment regimen № 2 was used, which differed from regimen № 1 by using a 50 % oil solution of tea tree essential oil in a similar dosage. The best therapeutic effect in the treatment of acute catarrhal endometritis was obtained using scheme № 2 using a 50 % oil solution of tea tree essential oil. Du¬ring the seven-day course of treatment, therapeutic effectiveness was obtained in 60.0 % of cases; prolongation of the course of therapy led to the recovery of all animals in this experimental group. The ave¬rage duration of treatment for the group was 8.0 days.

Detection of α-Thrombin with Platelet Glycoprotein Ibα (GP1bα) for the Development of a Coagulation Marker.

The detection of prothrombotic markers is crucial for understanding thromboembolism and assessing the effectiveness of anticoagulant drugs. α-Thrombin is a marker that plays a critical role in the coagulation cascade process. However, the detection of this enzymatic molecule was hindered by the absence of an efficient modality in the clinical environment. Previously, we reported that one α-thrombin interacts with two α-chains of glycoprotein Ib (GPIbα), i.e., multivalent protein binding (MPB), using bioresponsive hydrogel nanoparticles (nanogels) and optical microscopy. In this study, we demonstrated that GPIbα-mediated platforms led to the highly sensitive and quantitative detection of α-thrombin in various diagnostic systems. Initially, a bioresponsive nanogel-based surface plasmon resonance (nSPR) assay was developed that responds to the MPB of α-thrombin to GPIbα. The use of GPIbα for the detection of α-thrombin was further validated using the enzyme-linked immunosorbent assay, which is a gold-standard protein detection technique. Additionally, GPIbα-functionalized latex beads were developed to perform latex agglutination (LA) assays, which are widely used with hospital diagnostic instruments. Notably, the nSPR and LA assays exhibited a nearly 1000-fold improvement in sensitivity for α-thrombin detection compared to our previous optical microscopy method. The superiority of our GPIbα-mediated platforms lies in their stability for α-thrombin detection through protein-protein interactions. By contrast, assays relying on α-thrombin enzymatic activity using substrates face the challenge of a rapid decrease in postsample collection. These results suggested that the MPB of α-thrombin to GPIbα is an ideal mode for clinical α-thrombin detection, particularly in outpatient settings.

Role of Silver Nanoparticles for the Control of Anthelmintic Resistance in Small and Large Ruminants.

Helminths are considered a significant threat to the livestock industry, as they cause substantial economic losses in small and large ruminant farming. Their morbidity and mortality rates are also increasing day by day as they have zoonotic importance. Anthelmintic drugs have been used for controlling these parasites; unfortunately, due to the development of resistance of these drugs in helminths (parasites), especially in three major classes like benzimidazoles, nicotinic agonists, and macrocyclic lactones, their use is becoming very low. Although new anthelmintics are being developed, the process is time-consuming and costly. As a result, nanoparticles are being explored as an alternative to anthelmintics. Nanoparticles enhance drug effectiveness, drug delivery, and target specificity and have no resistance against parasites. Different types of nanoparticles are used, such as organic (chitosan) and inorganic (gold, silver, zinc oxide, iron oxide, and nickel oxide). One of them, silver nanoparticles (AgNPs), has unique properties in various fields, especially parasitology. AgNPs are synthesized from three primary methods: physical, chemical, and biological. Their primary mechanism of action is causing stress through the production of ROS that destroys cells, organs, proteins, and DNA parasites. The present review is about AgNPs, their mode of action, and their role in controlling anthelmintic resistance against small and large ruminants.

HKFGCN: A novel multiple kernel fusion framework on graph convolutional network to predict microbe-drug associations

Accumulating clinical studies have consistently demonstrated that the microbes in the human body closely interact with the human host, actively participating in the regulation of drug effectiveness. Identifying the associations between microbes and drugs can facilitate the development of drug discovery, and microbes have become a new target in antimicrobial drug development. However, the discovery of microbe-drug associations relies on clinical or biological experiments, which are not only time-consuming but also financially burdensome. Thus, the utilization of computational methods to predict microbe-drug associations holds promise for reducing costs and enhancing the efficiency of biological experiments. Here, we introduce a new computational method, called HKFGCN (Heterogeneous information Kernel Fusion Graph Convolution Network), to predict the microbe-drug associations. Instead of extracting feature from a single network in previous studies, HKFGCN separately extracts topological information features from different networks, and further refines them by generating Gaussian kernel features. HKFGCN consists of three main steps. Firstly, we constructed two similarity networks and a microbe-drug association network based on numerous biological data. Second, we employed two types of encoders to extract features from these networks. Next, Gaussian kernel features were obtained from the drug and microbe features at each layer. Finally, we reconstructed the bipartite microbe-drug graph based on the learned representations. Experimental results demonstrate the excellent performance of the HKFGCN model across different datasets using the cross-validation scheme. Additionally, we conduced case studies on human immunodeficiency virus, and the results were corroborated by existing literatures. The prediction model’s code is available at https://github.com/roll-of-bubble/HKFGCN.

Pain Science in Practice (Part 7): How Is Descending Modulation of Pain Measured?

SYNOPSIS: Understanding the descending pain modulatory system allows for a neuroscientific explanation of naturally occurring pain relief. Evidence from basic science and clinical studies on the effectiveness of drugs in certain patient groups led to pharmacological manipulation of the descending pain modulatory system for analgesia. Understanding mechanisms and theories helps clinicians make sense of chronic musculoskeletal pain. This editorial explains how test paradigms, including conditioned pain modulation, offset analgesia, and stress-induced analgesia work, provide an overview of a placebo analgesia circuitry, and discusses how evoking activity in the descending pain modulatory system using specific paradigms can give new insights into how specific treatments work to reduce pain. J Orthop Sports Phys Ther 2024;54(2):1-6. doi:10.2519/jospt.2024.12113.

The Effect of Therapy Regimen on Antitumor Efficacy of the Nanosomal Doxorubicin against Rat Glioblastoma 101.8.

One of the key problems of glioblastoma treatment is the low effectiveness of chemotherapeutic drugs. Incorporation of doxorubicin into PLGA nanoparticles allows increasing the antitumor effect of the cytostatics against experimental rat glioblastoma 101.8. Animal survival, tumor volume, and oncogene expression in tumor cells were compared after early (days 2, 5, and 8 after tumor implantation) and late (days 8, 11, and 14) start of the therapy. At late start, a significant increase in the expression of oncogenes Gdnf, Pdgfra, and Melk and genes determining the development of multidrug resistance Abcb1b and Mgmt was revealed. At early start of therapy, only the expression of oncogenes Gdnf, Pdgfra, and Melk was enhanced. Early start of treatment prolonged the survival time and increased tumor growth inhibition by 141.4 and 95.7%, respectively, in comparison with the untreated group; these differences were not observed in the group with late start of therapy. The results indicate that the time of initiation of therapy is a critical parameter affecting the antitumor efficacy of DOX-PLGA.

Potential inhibitory activities of phytoconstituents in Salvia miltiorrhiza against coronary heart disease drug targets using docking and ADMET studies

Coronary heart disease (CHD) is one of the leading causes of death worldwide. The effectiveness of the current drugs is still restricted due to high side effects; thus, it is urgently needed to discover novel compounds for drug development. In the field of drug discovery research, the main target receptors for chemotherapy are identified as ACE, PPAR-γ, HMGR, COX-2, and thrombin. In this study, docking simulations were performed for phytoconstituents of Salvia miltiorrhiza Bunge in searching for compounds with potential inhibitory activities against these proteins. As a result, six compounds were suggested as potential multitarget inhibitors and could be considered for further drug development studies based on docking conformation and ADMET property analysis.

Therapeutic Repurposing of Antidiabetic Drugs in Diabetes-associated Comorbidities

Background: Diabetic patients suffer from various comorbidities like cardiovascular diseases (CVDs), cancer, obesity, cognitive impairment, gout, leishmaniasis, etc. Objective: We aimed to review the pathological links between diabetes and its comorbidities and discuss the justification for using antidiabetic drugs in diabetes and associated comorbidities. Methods: Diabetic patients accompanied by comorbidities had to undergo a multidrug regimen apart from their common antidiabetic drugs, which affects their quality of life. There have been reports that some antidiabetic drugs ameliorate the comorbidities associated with diabetes. For instance, metformin is implicated in CVDs, cancer, as well as in cognitive impairment like Alzheimer's disease (AD); glyburide, a sulfonylurea, is found to be effective against leishmaniasis; and voglibose, an α- glucosidase inhibitor, is found to have suitable binding property against SARS-CoV-2 infection in diabetic patients. Targeting the comorbidities of diabetes with antidiabetic drugs may reduce the load of multidrug therapy in diabetic patients. Results: The effectiveness of antidiabetic drugs against some diabetic comorbidities between the two pathophysiological conditions, i.e., diabetes and its comorbidities, may be due to certain bidirectional links like inflammation, oxidative stress, disruption in the metabolic milieu and obesity. There are published reports of the repurposing of antidiabetic drugs for specific diseases, however, compiled repurposed reports of antidiabetic drugs for a wide range of diseases are scarce. Conclusion: In this review, we attempt to justify the use of antidiabetic drugs in diabetes and associated comorbidities.