Drug Side Research Articles

Potential of Moringa Oleifera Leaf (Moringa oleifera Lam.) as an Antibacterial: Systematic Literature Review

Background: The most common type of disease encountered is infectious disease. Antimicrobial substances are known as antibiotics. Misuse of antibiotics can lead to a number of negative outcomes, such as worsening of the drug's side effects, microorganisms becoming resistant to antibiotics, and even death. Methods: Researchers conducted a systematic review that aims to describe the review of the potential of Moringa leaves as antibacterial based on research that has been done. This literature review used six fulltext articles. The literature search technique was carried out on the PubMed and Google Scholar databases. Results: Moringa leaves contain various metabolite compounds such as flavonoids, alkaloids, saponins and tannins which are effective in inhibiting the growth of Gram-positive and Gram-negative bacteria. Moringa leaves can inhibit the growth of S. aureus, E. coli, P. aeruginosa, B. Subtilis, Proteus vulgaris, S. mutans, Streptococcus mutans, Staphylococcus epidedermis, and Salmonella sp. Conclusions: Moringa oleifera Lam. is often referred to as the “miracle tree” because all parts of the plant are beneficial for human health. Moringa leaves have antibacterial potential because they contain metabolite compounds that can inhibit bacterial resistance mechanisms, making them highly effective for treating infections.

Colchicine efficacy comparison at varying time points in the peri-operative period for coronary artery disease: a systematic review and meta-analysis of randomized controlled trials.

Over the years, it has been found that colchicine offers substantial benefits in secondary prevention in patients with coronary artery disease (CAD). We studied the effects of colchicine timing because there are no guidelines about when to provide it during the perioperative period for patients with CAD. Up to January 1, 2023, seven electronic literature databases were screened (including three English databases and four Chinese databases). Randomized controlled trials included only treatment with colchicine in the perioperative period of CAD. The Cochrane Evaluation Tool was used to judge the risk of bias in research. Statistical analysis was performed by Stata 16.0 software. We evaluated twelve studies that found colchicine to be effective in decreasing the occurrence of major adverse cardiac events (MACEs) (p < 0.00001), but it also raised the rate of adverse events (p = 0.001). Subgroup analysis showed the same benefit in lowering the incidence of MACE with continuous administration of a total daily dose of 0.5 mg postoperatively while minimizing drug-related side effects in the patients (p = 0.03). When it comes to preventing surgical stroke occurrences, postoperative administration is more effective (p = 0.006). While the effect of simultaneous preoperative and postoperative administration was marginally greater than other periods in reducing postoperative hs-CRP levels (p = 0.02). Colchicine, a traditional anti-inflammatory drug, also reduces the risk of MACE by reducing inflammation after PCI. Administration at different periods had no significant effect on decreasing the occurrence of MACE, but when administered postoperatively, we advise continuous administration with a total daily dose of 0.5 mg to obtain the same benefit while minimizing the drug's side effects. Postoperative administration is the better measure to prevent postoperative stroke events. Due to the effective anti-inflammatory effect of colchicine, we recommend its use as early as possible in the perioperative period and its continued use at low doses in the postoperative period. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316751, identifier CRD42022316751.

Microsponges: A Neoteric approach for the effective management of Osteoarthritis.

A microsponge delivery system (MDS) is a cutting-edge and distinctive method of structured medication delivery. Regulated drug distribution is now possible with the use of microsponge technology. Techniques for drug release are created specifically to distribute medications to the body's various locations. As a result, pharmacological therapy becomes more effective, and patient compliance significantly affects the health care system. MDS consists of porous microspheres with a substantially porous structure and a very small spherical shape, ranging in size from 5 to 300 microns. MDS is typically used to administer medications through topical channels, but new research has demonstrated the promise of this technique for parenteral, oral, and ocular drug delivery. Topical formulations are an attempt to manage diseases like osteoarthritis, rheumatoid arthritis, psoriasis, etc. While reducing the drug's side effects, MDS can readily change the pharmaceutical release shape and enhance formulation stability. Reaching the highest peak plasma concentration in the blood is the main goal of microsponge medication delivery. The ability of MDS to self-sterilize is by far the most notable quality. In countless studies, MDS is employed as an anti-allergic, anti-mutagenic, and nonirritant. This review covers the overview of microsponges along with their release mechanism. The article focuses on the marketed formulation of microsponges and patent data of the same. This review will be helpful for researchers working in MDS technology.

A Novel Topical Formulation of the Leishmaniasis Drug Glucantime as a Nanostructured Lipid Carrier-Based Hydrogel.

Leishmaniasis is a parasitic disease caused by Leishmania parasites. Meglumine antimoniate, or Glucantime, is the primary drug used to treat this disease. Glucantime with a standard painful injection administration route has high aqueous solubility, burst release, a significant tendency to cross into aqueous medium, rapid clearance from the body, and insufficient residence time at the injury site. Topical delivery of Glucantime can be a favorable option in the treatment of localized cutaneous leishmaniasis. In this study, a suitable transdermal formulation in the form of nanostructured lipid carrier (NLC)-based hydrogel containing Glucantime was prepared. In vitro drug release studies confirmed controllable drug release behavior for hydrogel formulation. An invivo permeation study on healthy BALB/C female mice confirmed appropriate penetration of hydrogel into the skin and sufficient residence time in the skin. In vivo performance of the new topical formulation on the BALB/C female mice showed a significant improvement in reduction of leishmaniasis wound size, lowering parasites number in lesions, liver, and spleen compared with commercial ampule. Hematological analysis showed a significant reduction of the drug's side effects, including variance of enzymes and blood factors. NLC-based hydrogel formulation is proposed as a new topical administration to replace the commercial ampule.

Liposomes containing azithromycin and green tea as an anti-acne treatment: Formulation and Characterization

Liposomes and other novel drug delivery carriers are highly adaptable, allowing for the distribution of a wide range of pharmacological compounds. The antibiotic azithromycin is widely regarded as the most effective treatment for acne. Lower efficacy or higher negative effects have led to decreased use of topical azithromycin. In this study, liposomes have been chosen because it is hypothesised that this may lessen the drug's side effects when used in conjunction with Azithromycin. Traditional herbal therapies have been intensively investigated as alternatives to conventional treatments for many ailments due to the possibility for side effects and antibiotic resistance from conventional pharmaceuticals. Thanks to its antibacterial qualities, green tea is one of the most effective natural therapies for acne. The lipid film hydration method was used to create drug-loaded liposomes, and the optimal component ratios were established. Liposomes were studied for their in-vitro drug release properties and characterised for their vesicle size, shape, encapsulation effectiveness, and drug content. Formulations F1 and F6, which included a 1:1 ratio of fat to cholesterol, showed the highest levels of encapsulation efficiency (69.5% and 66.2%, respectively) and in-vitro drug release (82.5 and 82.2 percent, respectively). Carbopol gel has been modified to include liposomal formulations, and the results have been compared to those of commercially available gels that do not use liposomes. Within 24 hours, the release of azithromycin (90.5%) was greater in the non liposomal marketed gel than in the liposomal gel (77.5% and 74.8%) of green tea. Green tea liposomes used in the formulation had a MIC value that was comparable to that of commercially available, non-liposomal gel. It was discovered that azithromycin was more effective than green tea in killing Micrococcus luteus.

EFFICACY AND SAFETY OF INTRAVENOUS ILOPROST IN THE TREATMENT OF RAYNAUD’S PHENOMENON AND DIGITAL ULCERS IN PATIENT WITH SYSTEMIC SCLERODERMA

Objectives: To evaluate the efficacy and safety of intravenous iloprost in the treatment of Raynaud’s phenomenon and digital ulcers in patients with SSc (systemic scleroderma).Methods: 31 patients with SSc were treated with intravenous iloprost in NHDV from April, 2017 to March, 2020. Evaluation was done after 2 weeks and included: width of ulcer, depth of ulcer, Raynaud phenomenon, laboratory tests, drug side effects.Results: VAS of Raynaud’s syndrome decreased markedly after iloprost infusion, from 71.5 points to 36.9 points. (p &lt; 0.001). The depth of ulcer improved markedly after 2 weeks of treatment, the rate of deep ulcers decreased from 20.6% to 1% (p &lt; 0.001). The ulcer width improved significantly after 2 weeks of treatment, the rate of grade 3 ulcers decreased from 35.1% to 13.4% (p &lt; 0.001). Side effects were found in 38.7% of patients, mainly headache (25.7%), flushing (9.7%); nausea/vomiting (6.5%); reaction at the site of infusion (6.5%). All side effects disappear when the infusion rate reduced. The majority of patients tolerated the drug at the maximum infusion rate (level 4), accounted for 61.3%.Conclusion: Intravenous iloprost is an effective and safe drug in the treatment of Raynaud’s phenomenon and digital ulcers in patients with SSc. The infusion process should be monitored according to the instructions.

Interpretable Ensembles of Classifiers for Uncertain Data With Bioinformatics Applications.

Data uncertainty remains a challenging issue in many applications, but few classification algorithms can effectively cope with it. An ensemble approach for uncertain categorical features has recently been proposed, achieving promising results. It consists in biasing the sampling of features for each model in an ensemble so that less uncertain features are more likely to be sampled. Here we extend this idea of biased sampling and propose two new approaches: one for selecting training instances for each model in an ensemble and another for sampling features to be considered when splitting a node in a Random Forest training. We applied these approaches to classify ageing-related genes and predict drugs' side effects based on uncertain features representing protein-protein and protein-chemical interactions. We show that ensembles based on our proposed approaches achieve better predictive performance. In particular, our proposed approaches improved the performance of a Random Forest based on the most sophisticated approach for handling uncertain data in ensembles of this kind. Furthermore, we propose two new approaches for interpreting an ensemble of Naive Bayes classifiers and analyse their results on our datasets of ageing-related genes and drug's side effects.

MICROSPONGES: AN INNOVATIVE TECHNIQUE FOR BIOMEDICAL RESEARCH

A microsponge delivery system (MDS) is a cutting-edge and distinctive method of structured drug delivery. Controlled drug delivery is now possible with the use of microsponge technology. MDS consists of porous microspheres with a substantially porous structure and a very small spherical shape, ranging in size from 5 to 300 microns. MDS is typically used to administer medications through topical channels, but new research has demonstrated the promise of this technique for parenteral, oral, and ocular drug delivery. While reducing the drug's side effects, MDS can readily change the pharmaceutical release shape and enhance formulation stability. Reaching the highest peak plasma concentration in the blood is the main goal of microsponge medication delivery. The most notable quality of MDS is their ability to self-sterilize. MDS is employed in countless studies as an anti-allergic, anti-mutagenic, and non-irritant. This review discusses formulation, eligibility requirements for medications to be included in MDS, formulation processes, evaluation criteria, and the function of MDS in the treatment of various illnesses. In the future, while researching MDS in other illnesses, this review will be quite helpful.

Efekat transkranijalne stimulacije direktnom strujom na kontrolu napada i prevenciju epilepsije

Introduction. Epilepsy is one of the most common neurological diseases. It is an uncontrollable neuronal activity of different parts of the brain leading to convulsion and/or fainting. Although epileptic seizure control and therapeutics have significant advances, 20% -30% of individuals still have uncontrolled seizures. Patients under the medication's control are not free from the drug's side effects and complications. Epileptic patients experience many different challenges. Transcranial direct current stimulation (tDCS) is a safe and non-invasive brain stimulation method applied in drug-resistant seizures and epilepsies. It transmits positive/negative electrical current toward deep brain parts, modulating their electrical activity. Methods. This is a review article. All relevant articles which were accessible were reviewed. The effectiveness of tDCS in preventing epilepsy in patients undergoing seizures was reviewed in this article. Conclusion. According to the studies, this method can probably be an auxiliary method in preventing and treating seizures. As epileptic seizures were induced and confirmed in some studies after the application of tDCS, the method should be cautiously applied.

Cabergoline - Dopamine Receptor Agonist

Background: Cabergoline is a potent dopamine receptor agonist used primarily for the treatment of disorders related to dopamine dysregulation. It acts by stimulating dopamine receptors in various regions of the brain and has been approved for the management of hyperprolactinemia, Parkinson's disease, and restless legs syndrome. Its unique pharmacological profile and tolerability make it a valuable therapeutic option in the field of neurology and endocrinology. Aim: The aim of this study was to investigate the efficacy and safety of cabergoline as a dopamine receptor agonist in the treatment of hyperprolactinemia, Parkinson's disease, and restless legs syndrome. The study also aimed to evaluate the impact of cabergoline on disease-specific symptoms and quality of life in patients with these conditions. Materials and Methods: A systematic literature review was conducted, encompassing peer-reviewed studies, clinical trials, and meta-analyses from reputable databases. Key search terms included "Cabergoline," "dopamine receptor agonist," "hyperprolactinemia," "Parkinson's disease," and "restless legs syndrome." Studies involving adult patients and reporting relevant outcomes, including symptom improvement and adverse events, were considered for analysis. Results: The analysis revealed that cabergoline effectively reduced prolactin levels in patients with hyperprolactinemia, leading to improvements in associated symptoms such as menstrual irregularities and galactorrhea. In Parkinson's disease, cabergoline demonstrated promising results in ameliorating motor symptoms, including rigidity, bradykinesia, and tremors. Additionally, studies investigating its role in restless legs syndrome showed a reduction in sensory and motor symptoms, leading to enhanced sleep quality. The drug's side effect profile was generally well-tolerated, with mild adverse events reported. Conclusion: Cabergoline, as a dopamine receptor agonist, emerges as a valuable therapeutic option for hyperprolactinemia, Parkinson's disease, and restless legs syndrome. It effectively addresses specific symptoms associated with these conditions and shows potential for improving patients' quality of life. The drug's favorable tolerability further supports its use in clinical practice. However, careful monitoring and further research are necessary to fully elucidate its long-term safety and effectiveness. Cabergoline's role in the treatment landscape of dopamine-related disorders holds promise for future advancements in neurology and endocrinology.

Design of New Personalized Therapeutic Approaches for Diffuse Large B-Cell Lymphoma through Gut Microbiome Profiling

Although front-line R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone) can improve clinical outcomes in diffuse large B-cell lymphoma (DLBCL), 20%-25% of patients relapse after initial response, within two years. Recent research on the gut microbiome (GM) in cancer has highlighted its importance in hematology. Indeed, GM can impact the onset and progression of cancer, as well as the outcomes of anticancer therapies and drug side effects.Fifty DLBCL patients undergoing front-line R-CHOP therapy were enrolled (ClinicalTrials.gov Identifier: NCT03797170, RF-2016-02363730). Feces were collected at baseline, before each therapy cycle and at response assessment (during both therapeutic course and follow-up). GM was profiled by 16S rRNA amplicon sequencing. Patients responding to first line will be followed up for two years after the end of treatment by fecal sampling every 6 months, in correspondence with disease re-evaluation. The GM of DLBCL patients before starting R-CHOP was compared with already-published data from healthy controls matched by geographical origin (Italy), gender and age. Patients showed less alpha diversity and some changes in composition, including notably an increase in Collinsella and a decrease in typically health-associated taxa, such as Faecalibacterium, Ruminococcus, Blautia and Bacteroides (Figure 1A-D). Concerning the GM dynamics though the R-CHOP therapy cycles (Figure 1E), no significant changes were observed but an overall reduction of several taxa starting from the fourth cycle. The compositional differences reported at baseline persisted until response assessment (following the last therapy cycle), while they partially reversed at the first follow-up (6 months after the end of therapy), with the recovery of healthy-like proportions for Bacteroides, Blautia, Faecalibacterium, Ruminococcus and Collinsella. All but two patients responded positively to therapy.The GM of DLBCL patients showed a significant alteration even before starting R-CHOP therapy, with reduced richness and dysbiotic compositional features. This imbalance was maintained until the fourth cycle, after which we detected an overall GM shrinkage. Six months after the end of therapy, the dysbiotic signatures were largely reversed, suggesting that GM resilience may be involved in the response to therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Drug-Disease Association Prediction Using Heterogeneous Networks for Computational Drug Repositioning.

Drug repositioning, which involves the identification of new therapeutic indications for approved drugs, considerably reduces the time and cost of developing new drugs. Recent computational drug repositioning methods use heterogeneous networks to identify drug–disease associations. This review reveals existing network-based approaches for predicting drug–disease associations in three major categories: graph mining, matrix factorization or completion, and deep learning. We selected eleven methods from the three categories to compare their predictive performances. The experiment was conducted using two uniform datasets on the drug and disease sides, separately. We constructed heterogeneous networks using drug–drug similarities based on chemical structures and ATC codes, ontology-based disease–disease similarities, and drug–disease associations. An improved evaluation metric was used to reflect data imbalance as positive associations are typically sparse. The prediction results demonstrated that methods in the graph mining and matrix factorization or completion categories performed well in the overall assessment. Furthermore, prediction on the drug side had higher accuracy than on the disease side. Selecting and integrating informative drug features in drug–drug similarity measurement are crucial for improving disease-side prediction.

Influence of using history of immune checkpoint inhibitor therapy for neutropenia caused by combination therapy of ramucirumab and docetaxel.

Recently, pretreatment with immune checkpoint inhibitors (ICIs) has been shown to enhance the therapeutic effects of the combination therapy of ramucirumab (RAM) and docetaxel (DTX); however, its influence on the drug's side effects remains unclear. This study investigated the influence of pretreatment with ICIs on the incidence of neutropenia caused by RAM + DTX therapy in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC who received RAM + DTX therapy at Gifu Prefectural General Medical Center between April 2016 and December 2020 were enrolled. Retrospective data regarding age, sex, performance status and detailed treatment history, among others, at treatment initiation were collected from the patients' electronic medical records. Additionally, data on the course number of RAM + DTX therapy, supportive therapy and blood biochemical parameters, including leukocyte and neutrocyte counts, during the treatment period were collected. We identified 41 patients receiving RAM + DTX therapy. Among the more than grade 3 adverse events caused by this therapy, neutropenia was the most common (78.1%). Despite the fact that all previous risk factors influencing this incidence rate had corresponded, the only factor influencing the incidence rate of neutropenia more than grade 3 was ICI treatment history. A difference in the incidence of neutropenia more than grade 3 in the Kaplan-Meier curve was observed between patients with and without ICI pretreatment history (p = 0.037). The pretreatment history of ICI therapy affects the incidence of neutropenia caused by RAM + DTX therapy in patients with NSCLC.

Abstract 307: Ponatinib loaded leukocyte-based nanoparticles: A new platform for treating osteosarcoma

Abstract The introduction of targeted anticancer drugs has revolutionized treatment. Multi-tyrosine kinase inhibitors (TKIs) are potential therapeutics targeting specific signaling pathways that contribute to cancer progression, including sarcomas. Osteosarcoma is the most common pediatric tumor with a worldwide incidence of 3.4 cases/million annually but without effective treatment. Of the TKIs, Ponatinib demonstrated potent anti-tumor activity; however, it received an FDA black box warning for potential side effects. New treatment and delivery systems must be identified to use Ponatinib clinically. Our laboratory developed novel biomimetic nanoparticles (NPs) synthesized from activated leukocytes called Leukosomes. Leukosomes maintain leukocyte tropism towards inflamed endothelium and can encapsulate and effectively release Ponatinib. We aimed to validate Leukosome technology’s therapeutic potential to specifically target and inhibit primary murine osteosarcoma growth and reduce detrimental side effects. In a 3D sarcosphere model, we observed effective penetration and internalization of NPs in both murine (RF379, 577) and human patient derived xenograft (PDX94, PDX202) osteosarcoma cell lines. Leukosome exhibited 20% increased targeting versus control liposomes. Cell viability decreased 20% after treatment with Ponatinib IC50. Leukosome-Ponatinib IC50 also induced complete inhibition of murine sarcosphere formation and ~60-80% reduction of cell viability. We developed an osteosarcoma orthotopic mouse model by intratibial injection of murine F420 osteosarcoma cells. After 3 weeks, tumor was detected and the mice were injected with Ponatinib NPs. Leukosome showed increased tumor targeting and penetration 1 and 3 hours post-NP injection. Intravenous tail injection of Ponatinib was lethal due to drug-related toxic effects, while intraperitoneal injection of Ponatinib was well tolerated. Conversely, intravenous injection of Ponatinib-loaded NPs did not show toxic effects. In vivo efficacy studies demonstrated that 3 weeks of Ponatinib treatment (2 treatments/week) inhibited tumor growth and increased survival. Similar results were also observed after Leukosome Ponatinib treatment, despite 10 times less Ponatinib in NPs than in free drug. Overall, these results show that leukocyte-derived membrane proteins enhance the accumulation of Ponatinib at the tumor site and surrounding inflamed tissue. While limited Ponatinib encapsulation in NPs remains an open challenge, this formulation underlies the possibility of reducing drug dosage and side effects. Thus, suggest Leukosome’s translational potential as a new targeted drug delivery approach with better outcomes and fewer complications for osteosarcoma patients. Citation Format: Federica Giordano, Stefania Lenna, Riccardo Rampado, Gherardo Baudo, Matteo Massaro, Ashley Rivera, Enrica De Rosa, Jason T. Yustein, Francesca Taraballi. Ponatinib loaded leukocyte-based nanoparticles: A new platform for treating osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 307.

Abstract 3011: Development of mitochondrial fission inhibitors in inducing non-apoptotic cell death in triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC) is the most aggressive subtype of metastatic breast cancer with poor clinical prognosis. Presently used neoadjuvant chemotherapy against TNBC, such as taxanes, and/or anthracyclines show an initial treatment response but follows with drug resistance, tumor relapse, side effects and high proclivity to develop metastases. Recent studies point out that targeting dysregulated mitochondrial dynamics, that is now linked to the tumor initiation, progression, and metastasis in TNBC, as an effective therapeutic strategy. In particular, mitochondrial fission factors such as dynamin-related protein 1 (Drp1) is upregulated in TNBC and is known to affect mitochondrial energetics and alter metabolism which favors tumor progression. We have designed and developed small molecule inhibitors to specifically target Drp1 as a viable therapeutic strategy for metastatic TNBC (mTNBC). We recently identified a new class of structurally constrained thienopyridine (TPH) probes, and particularly a new analog TPH104c that showed higher binding affinity in silico to Drp1 as compared to Mdivi-1, a weak inhibitor of Drp1. Surface plasmon resonance studies suggest that TPH104c binds with Drp1 with high affinity. Similarly, mechanistic studies using Western blotting and immunofluorescence analysis confirmed that TPH104c significantly downregulated the levels of total and phosphorylated form of Drp1 at serine 616 in MDAMB-231 and BT-20 TNBC cells. Interestingly, Drp1 inhibition by TPH104c led to a hitherto unreported form of caspase- and reactive oxygen species (ROS)-independent non-apoptotic form of cell death. Rather than shrinking in size, or formation of apoptotic blebs which are classical features of apoptosis, TPH104c treated TNBC cells were enlarged, rounded, and swollen in size. These cells eventually lost their proliferative ability and were significantly less confluent than control cells. Additionally, in TPH104c-treated cells, neither the mitochondrial membrane potential was lost, nor the caspases were activated as also indicated by a lack of rescue of cell death when incubated with pan-caspase inhibitor. Further studies are in progress to understand the role of Drp1 inhibition in the induction of non-apoptotic cell death which will further help to optimize an effective lead compound for the future pre-clinical development of promising anticancer agents targeting mTNBC. Citation Format: Saloni Malla, Shikha Kumari, David Terrero, Dayanidhi Raman, Amit K. Tiwari. Development of mitochondrial fission inhibitors in inducing non-apoptotic cell death in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3011.

In vitro anti-influenza assessment of anionic compounds ascorbate, acetate and citrate

BackgroundInfluenza A virus (IAV) infection remains a serious public health threat. Due to drug resistance and side effects of the conventional antiviral drugs, repurposing the available natural compounds with high tolerability and fewer side effects has attracted researchers’ attention. The aim of this study was to screen in vitro anti-influenza activity of three anionic compounds ascorbate, acetate, and citrate.MethodsThe non-cytotoxic concentration of the compounds was determined by MTT assay and examined for the activity against IAV in simultaneous, pre-, and post-penetration combination treatments over 1 h incubation on Madin-Darby Canine Kidney (MDCK) cell line. The virus titer and viral load were determined using hemagglutination assay (HA) and qPCR, respectively. Few pro-inflammatory and anti-inflammatory cytokines were evaluated at RNA and protein levels by qPCR and ELISA, respectively.ResultsThe non-cytotoxic concentrations of the ascorbate (200 mg/ml), acetate and citrate (both 3 mg/ml) reduced the viral titer by 6.5, 4.5, and 1.5 logs in the simultaneous combination treatment. The M protein gene copy number decreased significantly in simultaneous treatment (P < 0.01). The expression of cytokines was also affected by the treatment of these compounds.ConclusionsThese anionic compounds could affect the influenza virus load, thereby reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines levels.

DESIGN AND DEVELOPMENT OF A PHARMACOGENOMIC MODEL FOR BREAST CANCER TO STUDY THE VARIATION IN DRUG ACTION AND SIDE EFFECTS

Objective: The proneness of disease, as well as drug action and side effects, vary from person to person. This may be due to individual variations in the genome. The individual variation demands the need to design a population-specific 'predictive, preventive, participatory and personalized (p4)' pharmacogenomics drug molecule. The present work aims at designing a pharmacogenomic model for breast cancer to explain the individual variation in the proneness of the diseases and susceptibility towards drug action. Methods: The drug action and side effects of drugs were analyzed from clinical trial reports. The genes responsible for the drug action and the genes responsible for side effects have been identified and included in the variation analysis. The pharmacogenomic gene models have been designed by inducing population-specific genetic variations within the gene sequence. The 3D structures of the 'variation-specific' protein models have been generated by 'homology modelling.' These models have been used further for docking studies with the known drug molecules. The kinetic stability of the protein-ligand complexes obtained out of docking studies has been studied by the molecular dynamic simulation. Results: By the interaction studies and the computational analysis using the 'population-specific protein models,' the drug molecule, Capecitabine showed the highest binding affinity (–6.30kcal/mol) with the African population, Paclitaxel was found to be the most interacting with the European population with a binding affinity of–9.5603 kcal/mol, and Lapatinib is found to be the most suitable ligand for the American population with a binding affinity of–6.90 kcal/mol. These observations agree with the clinical trial data found in the 'ClinTrial database'. Conclusion: The designed models are found to be suitable for representing the respective population-specific target models. The interaction studies of known drug molecules with these population-specific target models correspond to the observations in the 'ClinTrial database.'

Clinical Pathways When Considering Antimicrobials for the Treatment of Mild-to-Moderate COVID-19.

Amidst a constrained supply of novel therapeutics for the outpatient treatment of mild-to-moderate COVID-19, clinicians face new challenges, especially among those practicing at overseas military treatment facilities. Although prescribers may be unfamiliar with these medications, appropriate use necessitates detailed query of patient symptomatology and familiarization with each drug's side effect profile. Risk stratification also requires careful consideration to patient-specific comorbidities and immunization status for determining whom to treat and how. In recognition of these complexities, a stepwise guide is provided here to aid clinicians in their management of outpatients with mild-to-moderate COVID-19.

Mining the Proteome of Toxoplasma Parasites Seeking Vaccine and Diagnostic Candidates.

Simple SummaryThe One Health concept to toxoplasmosis highlights that the health of humans is closely related to the health of animals and our common environment. Toxoplasmosis outcomes might be severe and fatal in patients with immunodeficiency, diabetes, and pregnant women and infants. Consequently, the development of effective vaccine and diagnostic strategies is urgent for the elimination of this disease. Proteomics analysis has allowed the identification of key proteins that can be utilized in the development of novel disease diagnostics and vaccines. This work presents relevant proteins found in the proteome of the life cycle-specific stages of Toxoplasma parasites. In fact, it brings together the main functionality key proteins from Toxoplasma parasites coming from proteomic approaches that are most likely to be useful in improving the disease management, and critically proposes innovative directions to finally develop promising vaccines and diagnostics tools.Toxoplasma gondii is a pathogenic protozoan parasite that infects the nucleated cells of warm-blooded hosts leading to an infectious zoonotic disease known as toxoplasmosis. The infection outcomes might be severe and fatal in patients with immunodeficiency, diabetes, and pregnant women and infants. The One Health approach to toxoplasmosis highlights that the health of humans is closely related to the health of animals and our common environment. The presence of drug resistance and side effects, the further improvement of sensitivity and specificity of serodiagnostic tools and the potentiality of vaccine candidates to induce the host immune response are considered as justifiable reasons for the identification of novel targets for the better management of toxoplasmosis. Thus, the identification of new critical proteins in the proteome of Toxoplasma parasites can also be helpful in designing and test more effective drugs, vaccines, and diagnostic tools. Accordingly, in this study we present important proteins found in the proteome of the life cycle-specific stages of Toxoplasma parasites that are potential diagnostic or vaccine candidates. The current study might help to understand the complexity of these parasites and provide a possible source of strategies and biomolecules that can be further evaluated in the pathobiology of Toxoplasma parasites and for diagnostics and vaccine trials against this disease.

Cytotoxic effects of chitosan nanoparticles containing Zataria multiflora essential oil against human breast and melanoma cells

BackgroundBreast cancer is the most common cancer among women, and melanoma incidence increases worldwide. The emergence of drug resistance and side effects of chemotherapy drugs has led to a great deal of attention being paid to the development of natural medicines, especially using essential oil. The preparation of essential oil-based nanoformulation has thus recently received more attention.ResultsIn this study, chitosan nanoparticles (ChiNPs) containing Zataria multiflora essential oil with a particle size of 177 ± 10 nm, a narrow particle size distribution (SPAN 0.96), and a cubic-like shape were first prepared. IC50 values of the prepared nanoformulation against human melanoma (A-375) and breast cancer cell lines (MCF-7 and MDA-MB-468) were obtained as 32 (12–84), 46 (32–67), and 105 (85–131) µg/mL. Besides, an electrospun polycaprolactone–polyethylene oxide scaffold was prepared as a dressing after treatment with the nanoformulation. Fourier transform infrared analysis confirmed the scaffold's preparation as well as successful loading of the essential oil in chitosan nanoparticles. Furthermore, the scaffold did not show a cytotoxic effect on A-375, MCF-7, and MDA-MB-468, and its surface was hydrophobic as the water contact angle with the surface was 136.5°.ConclusionsThe prepared prototype with natural ingredients and high efficacy could be considered for further consideration in vivo study or complementary medicine.Graphical abstract