Side Effects Of Drugs Research Articles

Impact of expected blood pressure reduction on patient preferences for pharmaceutical and renal denervation treatment.

Effective patient-centered care requires an adequate understanding of patient preferences for different therapeutic options. We modelled patient preference for blood pressure (BP) management by pharmaceutical or interventional treatments such as renal denervation in patients with different profiles of uncontrolled hypertension. Modeling was based on the findings from a previously conducted quantitative discrete choice experiment (DCE). The likelihood of selecting either an interventional treatment option or additional antihypertensive medication option was calculated for three patient profiles that represent the range of patients with hypertension commonly encountered in clinical practice: treatment-naive, patients with uncontrolled BP while on one to three antihypertensive medications, and patients with drug-resistant hypertension. Variables in the preference model were treatment attributes from the DCE study: expected reduction in office SBP with each treatment, duration of treatment effect, risk of reversible drug side effects from drugs, and risk of temporary pain and/or bruising or vascular injury from interventions. Values of the variables were derived from published clinical studies or expert opinion. The model predicted that the likelihood of choosing renal denervation over initiating pharmacotherapy was 17.2% for previously untreated patients, 23.7% for patients with moderate hypertension currently on pharmacotherapy, and 41.8% for patients with drug-resistant hypertension. The dominant variable driving preference in these models was the expected BP reduction. Patient preferences for intervention are greater when drug nonadherence or increased SBP reduction at 3 vs. 1 year are included in the model. Baseline BP, drug side effects, or risks of the procedure had little influence on decisions. Modeling using patient preference weights predicts that a substantial minority of patients favor an interventional treatment such as renal denervation over initiation or escalation of medications. Awareness of a patient's interest in device-based versus pharmaceutical strategies should inform the shared decision-making process for hypertension treatment.

Olanzapine-induced Metabolic Syndrome and its Association with -759C>T Polymorphism of the HTR2C Gene in Iraqi Schizophrenic Patients

The hazardous metabolic effects of treating schizophrenia patients with olanzapine comprise serotonin 2C receptor (5-HT2C) antagonists. Metabolic side effects of antipsychotic drugs, including lipid abnormalities, disturbed glucose metabolism, and weight gain, can have a major impact on treating psychiatric patients. The intent of this study was to investigate whether there is an associated link between the genetic polymorphism at -759C>T in the promoter region of the 5-hydroxytryptamine 2C receptor (HTR2C) gene and the metabolic syndrome driven by olanzapine in schizophrenia patients. A cross-sectional study that involved fifty hospitalized patients with schizophrenia. The patients were split into two groups (metabolic and non-metabolic) according to the classification criteria of the metabolic syndrome. The HTR2C promoter region polymorphism was identified through sequencing using the Sanger method after polymerase chain reaction amplification of the extracted deoxyribonucleic acid. Even though none of the genotypes of the -759C>T variant are associated with the propensity to develop metabolic syndrome, there is a significant difference in the -759C>T variant's T allele (p-value = 0.001). The presence of the T allele in the -759 C/T variant was significantly associated with developing metabolic syndrome. Keywords: Schizophrenic patients, Olanzapine, Genetic polymorphism, 5-hydroxytryptamine 2C receptor (HTR2C) gene, -759C>T.

Mycofenolate-induced ileocolitis.

Terminal ileitis is a common finding in clinical practice and is often associated with Crohn's disease. However, other pathologies must be considered particularly those resulting from side effects of drugs. We report a case of an 18-year-old female that underwent renal transplant under mycophenolate sodium, tacrolimus, and prednisolone admitted for abdominal pain, diarrhea and weight loss. Abdominal ultrasound revealed terminal ileum wall thickness, extending through 6,6 cm, while a subsequent Ileocolonoscopy revealed normal ileal mucosae but congestive cecum mucosae with superficial ulcers. Histology revealed unspecific chronic inflammation. Under the hypothesis of drug-induced enterocolitis, and after multidisciplinary discussion, mycophenolate sodium was suspended, with a rapid recovery without further treatment. This case highlights the challenge of diagnosing ileocolitis and demonstrates that MS-induced lesions can present clinical and endoscopic changes similar to those seen in Crohn's disease. Although enteric-coated MS has delayed absorption from the GI tract compared to MMF, which might reduce GI adverse events, this difference does not seem to be statistically significant.

A qualitative study on reasons for women’s loss and resumption of Option B plus care in Ethiopia

Loss to follow-up (LTFU) from Option B plus, a lifelong antiretroviral therapy (ART) for pregnant women living with human immunodeficiency virus (HIV), irrespective of their clinical stage and CD4 count, threatens the elimination of vertical transmission of the virus from mothers to their infants. However, evidence on reasons for LTFU and resumption after LTFU to Option B plus care among women has been limited in Ethiopia. Therefore, this study explored why women were LTFU from the service and what made them resume or refuse resumption after LTFU in Ethiopia. An exploratory, descriptive qualitative study using 46 in-depth interviews was employed among purposely selected women who were lost from Option B plus care or resumed care after LTFU, health care providers, and mother support group (MSG) members working in the prevention of mother-to-child transmission unit. A thematic analysis using an inductive approach was used to analyze the data and build subthemes and themes. Open Code Version 4.03 software assists in data management, from open coding to developing themes and sub-themes. We found that low socioeconomic status, poor relationship with husband and/or family, lack of support from partners, family members, or government, HIV-related stigma, and discrimination, lack of awareness on HIV treatment and perceived drug side effects, religious belief, shortage of drug supply, inadequate service access, and fear of confidentiality breach by healthcare workers were major reasons for LTFU. Healthcare workers' dedication to tracing lost women, partner encouragement, and feeling sick prompted women to resume care after LTFU. This study highlighted financial burdens, partner violence, and societal and health service-related factors discouraged compliance to retention among women in Option B plus care in Ethiopia. Women's empowerment and partner engagement were of vital importance to retain them in care and eliminate vertical transmission of the virus among infants born to HIV-positive women.

Molecular Communication-Based Intelligent Dopamine Rate Modulator for Parkinson's Disease Treatment.

Parkinson's disease (PD) is a progressive neurodegenerative disease, and it is caused by the loss of dopaminergic neurons in the basal ganglia (BG). Currently, there is no definite cure for PD, and available treatments mainly aim to alleviate its symptoms. Due to impaired neurotransmitter-based information transmission in PD, molecular communication-based approaches can be employed as potential solutions to address this issue. Molecular Communications (MC) is a bio-inspired communication method utilizing molecules to carry information. This mode of communication stands out for developing biocompatible nanomachines for diagnosing and treating, particularly in addressing neurodegenerative diseases like PD, due to its compatibility with biological systems. This study presents a novel treatment method that introduces an Intelligent Dopamine Rate Modulator (IDRM), which is located in the synaptic gap between the substantia nigra pars compacta (SNc) and striatum to compensate for insufficiency dopamine release in BG caused by PD. For storing dopamine in the IDRM, dopamine compound (DAC) is swallowed and crossed through the digestive system, blood circulatory system, blood-brain barrier (BBB), and brain extracellular matrix uptakes with IDRMs. Here, the DAC concentration is calculated in these regions, revealing that the required exogenous dopamine consistently reaches IDRM. Therefore, the perpetual dopamine insufficiency in BG associated with PD can be compensated. This method reduces drug side effects because dopamine is not released in other brain regions. Unlike other treatments, this approach targets the root cause of PD rather than just reducing symptoms.

Effect of Circadian Rhythm Modulated Blood Flow on Nanoparticle based Targeted Drug Delivery in Virtual In Vivo Arterial Geometries.

A novel integration of nanoparticle-based drug delivery framework with shear-rate dependent blood flow model is presented. The framework is comprised of a unique combination of mechanics-based dispersion model, an asperity model for endothelium surface roughness, and a stochastic nanoparticle-endothelial cell adhesion model. Simulations of MRI based in vivo carotid artery system showcase the effects of vessel geometry on nanoparticle adhesion and retention at the targeted site. Vessel geometry and target site location impact nanoparticle adhesion; curved and bifurcating regions favor local accumulation of drug. It is also shown that aligning drug administration with circadian rhythm and sleep cycle can enhance the efficacy of drug delivery processes. These simulations highlight the potential of the computational modeling for exploring circadian rhythm modulated blood flow for targeted drug delivery while minimizing the in vivo experimentation.

The Protective Effect of GnRH Agonist Triptorelin on the Histomorphometric Parameters of the Utero-ovarian Tissue in the Doxorubicin- and Cyclophosphamide-treated Mice.

One of the common side effects of chemotherapy drugs is ovarian failure and uterine dysfunction, which can occur after the administration of doxorubicin and/or cyclophosphamide. In clinics, gonadotropin-releasing hormone agonists (GnRHa) are used to modulate the toxic effect of chemotherapy and intercept infertility with some controversy and limited histological knowledge. This study aimed to evaluate the serological and histological features of protective effects of triptorelin, (GnRHa), on utero-ovarian tissue in the mice treated with cyclophosphamide and/or doxorubicin. Forty-eight female BALB/c mice were randomly divided into 8 groups as follows: Group I: normal saline; Group II: triptorelin; Group III: cyclophosphamide; Group IV: doxorubicin; Group V: cyclophosphamide + doxorubicin; and Groups VI, VII, and VIII: after injection of cyclophosphamide, doxorubicin, or cyclophosphamide + doxorubicin, administration of triptorelin (1 mg/kg; intraperitoneally) for 15 consecutive days, respectively. On the 21st day, the ovaries and uterine horns were dissected and weighed. Then, tissue processing and staining were performed for further histological and stereological studies. Triptorelin treatment in the damaged groups significantly increased the number of primordial and pre-antral follicles and granulosa cells. It decreased the number of atretic follicles compared to cyclophosphamide and/or doxorubicin-treated groups (P < 0.05). Triptorelin also significantly improved the volume of the ovary, cortex, medulla, oocytes in the primordial and antral follicles, uterus, endometrium, myometrium, uterine glands, and endometrial blood vessels in the damaged groups (P < 0.05). Triptorelin treatment prevents the destructive effects of cyclophosphamide and/or doxorubicin on utero-ovarian tissue.

Clinical reasoning amongst paramedics using nebulised β₂ agonists to treat acute asthma exacerbations: a qualitative study

The heterogeneous nature of asthma results in a wide range of presentations during exacerbation. Despite UK pre-hospital management guidelines focusing on β₂ agonists, variables such as cause, severity, underlying health, comorbidities, and drug side effects can often make emergency treatment optimisation difficult. This article examines paramedics’ methods of observing, perceiving, interpreting, and treating asthma with β₂ agonists, often acting on limited information in rapidly evolving situations. We recruited paramedics from a single UK National Health Service ambulance Trust for qualitative semi-structured interviews. Responses underwent framework analysis to identify data similarities and differences. Fifteen qualitative interviews with paramedics revealed three main themes affecting patient management: clinician experience of presentation, adaptation of patient management approaches, and severity of side effects. Paramedics felt their ability to manage various asthma presentations was enhanced through guideline adaptation based on their own clinical experience and understanding of β₂ agonist side effects, allowing tailored responses based on a set of reinforcing factors. Inductive analysis revealed additional complexities within these themes, such as anxiety and diabetes, which may influence β₂ agonist administration and result in multiple care pathways being initiated during exacerbation. Paramedic care mirrors asthma’s complexity, accounting for a range of characteristics. A dynamic, critically thought approach enables patient management to be based on the presenting conditions rather than strict adherence to a single algorithm. Comprehending the complexities and variables in treatment can be crucial to how paramedics rationalise their treatment and optimise the care provided.

Molecular Insights into the Anticancer Activity of Withaferin-A: The Inhibition of Survivin Signaling.

Survivin, a member of the IAP family, functions as a homodimer and inhibits caspases, the key enzymes involved in apoptosis. Several Survivin inhibitors, including YM-155, Debio1143, EM1421, LQZ-7I, and TL32711, have emerged as potential anticancer drugs awaiting validation in clinical trials. Due to the high cost and adverse side effects of synthetic drugs, natural compounds with similar activity have also been in demand. In this study, we conducted molecular docking assays to evaluate the ability of Wi-A and Wi-N to block Survivin dimerization. We found that Wi-A, but not Wi-N, can bind to and prevent the homodimerization of Survivin, similar to YM-155. Therefore, we prepared a Wi-A-rich extract from Ashwagandha leaves (Wi-AREAL). Experimental analyses of human cervical carcinoma cells (HeLa and ME-180) treated with Wi-AREAL (0.05-0.1%) included assessments of viability, apoptosis, cell cycle, migration, invasion, and the expression levels (mRNA and protein) of molecular markers associated with these phenotypes. We found that Wi-AREAL led to growth arrest mediated by the upregulation of p21WAF1 and the downregulation of several proteins (CDK1, Cyclin B, pRb) involved in cell cycle progression. Furthermore, Wi-AREAL treatment activated apoptosis signaling, as evidenced by reduced PARP-1 and Bcl-2 levels, increased procaspase-3, and elevated Cytochrome C. Additionally, treating cells with a nontoxic low concentration (0.01%) of Wi-AREAL inhibited migration and invasion, as well as EMT (epithelial-mesenchymal transition) signaling. By combining computational and experimental approaches, we demonstrate the potential of Wi-A and Wi-AREAL as natural inhibitors of Survivin, which may be helpful in cancer treatment.

Development of non-sedating benzodiazepines with in vivo antischistosomal activity.

The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad-spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resistance or treatment failure. One promising lead that has shown efficacy in animal models and a human clinical trial is the benzodiazepine meclonazepam, discovered by Roche in the 1970s. Meclonazepam was not brought to market because of dose-limiting sedative side effects. However, the human target of meclonazepam that causes sedation (GABAARs) is not orthologous to the parasite targets that cause worm death. Therefore, we were interested in whether the structure of meclonazepam could be modified to produce antiparasitic benzodiazepines that do not cause host sedation. We synthesized 18 meclonazepam derivatives with modifications at different positions on the benzodiazepine ring system and tested them for in vitro antiparasitic activity. This identified five compounds that progressed to in vivo screening in a murine model, two of which cured parasite infections with comparable potency to meclonazepam. When these two compounds were administered to mice that were run on the rotarod test, both were less sedating than meclonazepam. These findings demonstrate the proof of concept that meclonazepam analogs can be designed with an improved therapeutic index and point to the C3 position of the benzodiazepine ring system as a logical site for further structure-activity exploration to further optimize this chemical series.

Precision Treatment of Colon Cancer Using Doxorubicin-Loaded Metal-Organic-Framework-Coated Magnetic Nanoparticles.

Due to the limited efficacy and evident side effects of traditional chemotherapy drugs attributed to their lack of specificity and selectivity, novel strategies are essential for improving cancer treatment outcomes. Here, we successfully engineered Fe3O4 magnetic nanoparticles coated with zeolitic imidazolate framework-8 (ZIF-8). The resulting nanocomposite (Fe3O4@ZIF-8) demonstrates efficient adsorption of a substantial amount of doxorubicin (DOX) due to the porous nature of ZIF-8. The drug-loaded nanoparticles, Fe3O4@ZIF-8/DOX, exhibit significant accumulation at the tumor site in SW620 colon-cancer-bearing mice when guided by an external magnetic field. Within the acidic microenvironment of the tumor, the ZIF-8 framework collapses, releasing DOX and effectively inducing tumor cell death, thereby inhibiting cancer progression while not causing undesired side effects, as confirmed by a variety of in vitro and in vivo characterizations. In comparison to free DOX, Fe3O4@ZIF-8/DOX nanoparticles show superior efficacy in colon cancer treatment. Our findings suggest that Fe3O4@ZIF-8 holds promise as a carrier for small-molecule drug adsorption and its ferromagnetic properties provide drug targeting capabilities, thereby enhancing therapeutic effects on tumors at the same drug dosage. With excellent biocompatibility, Fe3O4@ZIF-8 demonstrates potential as a drug carrier in targeted cancer chemotherapy. Our work suggests that a combination of magnetic targeting and acid-responsiveness holds great promise for advancing targeted cancer therapy in precision nanomedicine.

Electrochemotherapy and Calcium Electroporation on Hepatocellular Carcinoma Cells: An In-Vitro Investigation

PurposeElectrochemotherapy, clinically established for treating (sub)cutaneous tumors, has been standardized in the framework of the European Standard Operating Procedure on Electrochemotherapy (ESOPE). Due to common side effects of chemotherapeutic drugs, recent advances focus on non-cytotoxic agents, like calcium, to induce cell death (calcium electroporation). Therefore, this study aims to determine the efficacy of electrochemotherapy with bleomycin or cisplatin, or calcium electroporation on human hepatocellular carcinoma cells (HepG2) in vitro using the ESOPE protocol.MethodsHepG2 cell viability was measured with a MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay after electrochemotherapy with the chemotherapeutic drugs bleomycin or cisplatin (0–20 µM), or after calcium electroporation (0–20 mM), to determine its efficacy on HepG2 cells in vitro using the ESOPE protocol (8 rectangular pulses, 1000 V/cm, 100 µs) compared to non-electroporated drug treatment.ResultsCell viability was significantly lower in electroporated samples, compared to their non-electroporated controls (27–75% difference). Electrochemotherapy with bleomycin and calcium electroporation, reached (almost) complete cell death (− 1 ± 3% and 2.5 ± 2%), in the lowest concentration of 2.5 µM and 2.5 mM, respectively. Electrochemotherapy with 2.5 µM cisplatin, significantly decreased cell viability to only 68% (± 7%).ConclusionElectrochemotherapy with bleomycin or cisplatin, or calcium electroporation were more effective in reducing the HepG2 cell viability in vitro using the ESOPE protocol compared to the non-electroporated drug treatments alone. When comparing electrochemotherapy, HepG2 cells are more sensitive to bleomycin than cisplatin, in similar concentrations. Calcium electroporation has the same effectiveness as electrochemotherapy with bleomycin, but calcium potentially has a better safety profile and several treatment advantages.Graphical

Pharmacists Impact on Promoting the Public Health

Because they can guarantee that patients receive safe and effective medications, pharmacists are essential members of the healthcare team. In an effort to maximize patient results, they work in tandem with other medical specialists to evaluate pharmacological therapy, dispense medication, counsel patients on drug interactions and side effects, and monitor medication schedules. Pharmacists also give patients advice on managing illnesses, changing lifestyles, and adhering to medication regimens. The range of work that pharmacists do has expanded with the emergence of numerous global health issues. Safe and efficient drug usage by community and clinical pharmacists is necessary to provide the best possible patient outcomes. The public is still ignorant about the pharmacist's contribution to national and international health, nevertheless. They also perform drug use assessments, act as drug information specialists, and offer advice on the proper choice and dosage of medications. Pharmacists play a critical role in healthcare organizations as they strive to reduce prescription errors, enhance patient safety, and manage costs. The pharmacist can improve public health in a beneficial way. Thus far, the rise in the importance of pharmacists has been more influenced by the expansion of patient services than by a population-based approach to health. Pharmacists may find that integrating the five public health core competencies—social and behavioral science, health policy and administration, epidemiology, biostatistics, and environmental health sciences—into their pharmacy practice increases their efficacy and influence.

Knowledge and perception among adults of their congenital heart disease: A single center cross-sectional study

Introduction and objectiveCongenital heart disease (CHD) is a complex condition requiring a multidisciplinary approach. It is crucial that adults with CHD (CHD) have adequate knowledge of their condition, enabling them to engage in their healthcare decisions and self-management. We aimed to investigate knowledge and perception among adults of their CHD. MethodsSingle-center, observational, cross-sectional study. A 25-item adapted survey of Leuven Questionnaire for CHD was used to assess four main domains: (1) disease and treatment, (2) endocarditis and preventive measures, (3) physical activity and (4) reproductive issues. ResultsOne hundred forty-eight patients participated in the study. Patients had a significant lack of knowledge localizing their heart defect, recognizing drug side effects, acting in case of experiencing drug side effects, recognizing at least two symptoms of clinical deterioration, to adequately define endocarditis and most typical signs and risk factors, to acknowledge the hereditary nature of their CHD and risk of clinical deterioration during pregnancies. Patients with an education level ≥12th grade have higher knowledge in various items and, overall, the complexity of CHD was not associated with a better performance. ConclusionThis study highlights the existing knowledge gaps among adults with CHD. It underscores the need for tailored information and structured educational programs to improve management. By addressing these challenges, healthcare providers can enhance patient outcomes, improve quality of life, and promote long-term well-being for individuals with CHD.

Inhibition of HDAC8 mitigates AKI by reducing DNA damage and promoting homologous recombination repair.

Nephrotoxicity is a major side effect of platinum-based antineoplastic drugs, and there is currently no available therapeutic intervention. Our study suggests that targeting histone deacetylase 8 could be a potential treatment for cisplatin-induced acute kidney injury (AKI). In a murine model of AKI induced by cisplatin, the administration of PCI-34051, a selective inhibitor of HDAC8, resulted in significant improvement in renal function and reduction in renal tubular damage and apoptosis. Pharmacological inhibition of HDAC8 also decreased caspase-3 and PARP1 cleavage, attenuated Bax expression and preserved Bcl-2 levels in the injured kidney. In cultured murine renal epithelial cells (mRTECs) exposed to cisplatin, treatment with PCI-34051 or transfection with HDAC8 siRNA reduced apoptotic cell numbers and diminished expression of cleaved caspase-3 and PARP1; conversely, overexpression of HDAC8 intensified these changes. Additionally, PCI-34051 reduced p53 expression levels along with those for p21, p-CDK2 and γ-H2AX while preserving MRE11 expression in the injured kidney. Similarly, pharmacological and genetic inhibition of HDAC8 reduced γ-H2AX and enhanced MRE11 expression; conversely, HDAC8 overexpression exacerbated these changes in mRTECs exposed to cisplatin. These results support that HDAC8 inhibition attenuates cisplatin-induced AKI through a mechanism associated with reducing DNA damage and promoting its repair.

Will Precision Medicine Meet Digital Health? A Systematic Review of Pharmacogenomics Clinical Decision Support Systems Used in Clinical Practice.

Digital health, an emerging scientific domain, attracts increasing attention as artificial intelligence and relevant software proliferate. Pharmacogenomics (PGx) is a core component of precision/personalized medicine driven by the overarching motto "the right drug, for the right patient, at the right dose, and the right time." PGx takes into consideration patients' genomic variations influencing drug efficacy and side effects. Despite its potentials for individually tailored therapeutics and improved clinical outcomes, adoption of PGx in clinical practice remains slow. We suggest that e-health tools such as clinical decision support systems (CDSSs) can help accelerate the PGx, precision/personalized medicine, and digital health emergence in everyday clinical practice worldwide. Herein, we present a systematic review that examines and maps the PGx-CDSSs used in clinical practice, including their salient features in both technical and clinical dimensions. Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and research of the literature, 29 relevant journal articles were included in total, and 19 PGx-CDSSs were identified. In addition, we observed 10 technical components developed mostly as part of research initiatives, 7 of which could potentially facilitate future PGx-CDSSs implementation worldwide. Most of these initiatives are deployed in the United States, indicating a noticeable lack of, and the veritable need for, similar efforts globally, including Europe.

Rationally designed BCR-ABL kinase inhibitors for improved leukemia treatment via covalent and pro-/dual-drug targeting strategies

BackgroundChronic Myeloid Leukemia (CML) is a blood cancer that remains challenging to cure due to drug resistance and side effects from current BCR-ABL inhibitors. There is an urgent need for novel and more effective BCR-ABL targeting inhibitors and therapeutic strategies to combat this deadly disease. MethodWe disclose an “OH-implant” strategy to improve a noncovalent BCR-ABL inhibitor, PPY-A, by adding a hydroxyl group to its scaffold. By taking advantage of this OH “hot spot”, we designed a panel of irreversible covalent kinase inhibitors and hypoxia-responsive pro-/dual-drugs, and their biological activities were studied in vitro, in cellulo and in vivo. ResultThe resulting compound B1 showed enhanced solubility and biological activity. B4 achieved sustained BCR-ABL inhibition by forming a stable covalent bond with ABL kinase. Hypoxia-responsive prodrug P1 and dual-drugs D1/D2/D3 demonstrated significant anti-tumor effects under hypoxic conditions. The in vivo studies using K562-xenografted mice showed that B1 displayed superior antitumor activity than PPY-A, while P1 and D3 offered better safety profiles alongside significant tumor control. ConclusionWe have successfully developed a chemical biology approach to convert a known noncovalent BCR-ABL inhibitor into more potent and safer inhibitors through covalent and pro-/dual-drug targeting strategies. Our “OH-implant” approach and the resulting drug design strategies have general applicability and hold promise for improvement the performance of various other reported drugs/drug candidates, thereby providing advanced medicines for disease treatment.

A pH-Responsive Drug-Delivery System Based on Apatinib-Loaded Metal-Organic Frameworks for Ferroptosis-Targeted Synergistic Anti-Tumor Therapy.

The efficacy of systemic therapy for hepatocellular carcinoma (HCC) is limited mainly by the complex tumor defense mechanism and the severe toxic side-effects of drugs. The efficacy of apatinib (Apa), a key liver cancer treatment, is unsatisfactory due to inadequate targeting and is accompanied by notable side-effects. Leveraging nanomaterials to enhance its targeting represents a crucial strategy for improving the effectiveness of liver cancer therapy. A metal polyphenol network-coated apatinib-loaded metal-organic framework-based multifunctional drug-delivery system (MIL-100@Apa@MPN) was prepared by using metal-organic frameworks (MOFs) as carriers. The nanoparticles (NPs) were subsequently characterized using techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), zeta potential measurements, and particle size analysis. In vitro experiments were conducted to observe the drug release kinetics and cytotoxic effects of MIL-100@Apa@MPN on HepG2 cells. The in vivo anti-tumor efficacy of MIL-100@Apa@MPN was evaluated using the H22 tumor-bearing mouse model. The formulated MIL-100@Apa@MPN demonstrates remarkable thermal stability and possesses a uniform structure, with measured drug-loading (DL) and encapsulation efficiency (EE) rates of 28.33% and 85.01%, respectively. In vitro studies demonstrated that HepG2 cells efficiently uptake coumarin-6-loaded NPs, and a significant increase in cumulative drug release was observed under lower pH conditions (pH 5.0), leading to the release of approximately 73.72% of Apa. In HepG2 cells, MIL-100@Apa@MPN exhibited more significant antiproliferative activity compared to free Apa. In vivo, MIL-100@Apa@MPN significantly inhibited tumor growth, attenuated side-effects, and enhanced therapeutic effects in H22 tumor-bearing mice compared to other groups. We have successfully constructed a MOF delivery system with excellent safety, sustained-release capability, pH-targeting, and improved anti-tumor efficacy, highlighting its potential as a therapeutic approach for the treatment of HCC.

Kajian Perilaku Kepatuhan Medikasi Pasien Tuberculosis Paru di Kabupaten Ngawi: Sebuah Model Matematis

Background: Tuberculosis (TB) is currently still a health issue in Indonesia. Indonesia is the country that contributes the second largest number of tuberculosis cases after India. Ngawi is one of the cities in East Java Province with a large number of tuberculosis cases. In 2022, tuberculosis cases in Ngawi Regency will double from the previous year with the death rate also increasing from the previous year. This shows that tuberculosis control in Ngawi Regency has not been effective. Efforts are needed to increase medication compliance in tuberculosis sufferers so that therapeutic success can be achieved so that the death rate and tuberculosis transmission rate can be reduced.Methods: This research is an analytical observational study with a cross sectional research design which aims to create a mathematical model of medication adherence in pulmonary TB sufferers in Ngawi Regency. This research involved 102 pulmonary TB sufferers at Dr. Soeroto Hospital, Widodo Hospital and Ngawi Regency Health Center. Pulmonary TB sufferers were selected using a purposive sampling technique. Data were analyzed using multiple logistic regression tests.Result: Based on interviews conducted with 102 respondents, the results obtained were that the variables age, length of treatment, motivation to recover, self-perception, knowledge, access to health facilities, medication assistance, family support, drug side effects and health facility administration were candidates for bivariate testing.Conclusion : The variables of self-perception, knowledge, family support and health facility administration are the dominant factors influencing medication compliance in pulmonary TB sufferers in Ngawi Regency in 2023.

Experimental and computational insights of Albizia amara phytoconstituents targeting anthranilate phosphoribosyltransferase from Malassezia globosa

The fungus Malassezia globosa is often responsible for superficial mycoses posing significant treatment challenges because of the unfavourable side effects of available antifungal drugs. To reduce potential hazards to the host and overcome these hurdles, new therapeutic medicines must be developed that selectively target enzymes unique to the pathogen. This study focuses on the enzyme anthranilate phosphoribosyltransferase (AnPRT), which is vital to M. globosa's tryptophan production pathway. To learn more about the function of the AnPRT enzyme, we modeled, validated, and simulated its structure. Moreover, many bioactive components were found in different extracts from the plant Albizia amara after phytochemical screening. Interestingly, at doses ranging from 500 to 2000 µg/ml, the chloroform extract showed significant antifungal activity, with inhibition zones measured between 11.0 ± 0.0 and 25.6 ± 0.6 mm. According to molecular docking analyses, the compounds from the active extract, particularly 2-tert-Butyl-4-isopropyl-5-methylphenol, interacted with the AnPRT enzyme's critical residues, ARG 205 and PHE 214, with an effective binding energy of -4.9 kcal/mol. The extract's revealed component satisfies the requirements for drug-likeness and shows promise as a strong antifungal agent against infections caused by M. globosa. These findings imply that using plant-derived chemicals to target the AnPRT enzyme is a viable path for the creation of innovative antifungal treatments.