Key Therapeutic Agents Research Articles

Key Therapeutic Agents for Thymic Carcinoma in Real-world Clinical Practice.

Thymic carcinoma is a rare cancer with poor prognosis in unresectable cases. Treatment efficacy of carboplatin+paclitaxel (CP), lenvatinib, S-1, and sunitinib remains uncertain, with some patients experiencing increased post-treatment liver metastasis. We performed a retrospective analysis of patients with metastatic thymic carcinoma who received chemotherapy between 2006 and 2023 at the National Cancer Center Hospital. We evaluated the clinical outcomes [progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), liver metastasis response rate (LMRR), and liver metastasis control rate (LMCR)] of CP, lenvatinib, S-1, and sunitinib. A total of 178 patients were evaluated, with 78.1% having stage IV disease. Most patients had squamous cell carcinoma (85.4%), and 39 patients had liver metastases (21.9%). The most frequently administered treatments as 1st-, 2nd-, and 3rd- line were CP (85.5%), S-1 (58.3%), and sunitinib (28.4%). The median PFS was 6.8, 9.4, 4.5, and 3.4 months in CP, lenvatinib, S-1, and sunitinib. CP showed an ORR of 41.6% and LMRR of 40.9%. The reverse response, in which only liver metastasis increased despite shrinkage of other lesions, was observed in lenvatinib (20%), S-1 (3.4%), and sunitinib (8.3%). CP and lenvatinib provided effective outcomes in metastatic thymic carcinoma, aligning with previous findings. S-1 and sunitinib also show clinical activity but with variable responses in liver metastases. These results highlight the importance of tailored treatment strategies, particularly for patients with liver involvement.

Evaluating the Efficacy of Steroids in Autoimmune Disorders: A Comprehensive Review of Case Studies in Rheumatoid Arthritis, Lupus, and Asthma

This comprehensive review evaluates the efficacy of corticosteroids in managing three prominent autoimmune disorders: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and asthma. Autoimmune disorders are characterized by the immune system’s misdirected attack on healthy tissues, leading to chronic inflammation and debilitating symptoms. Corticosteroids have long been recognized as key therapeutic agents due to their potent anti-inflammatory and immunosuppressive properties. This review synthesizes findings from various case studies and clinical trials, highlighting the benefits of corticosteroids in reducing disease activity and improving patient outcomes across these conditions. However, the long-term use of corticosteroids is associated with significant adverse effects, including osteoporosis, metabolic disturbances, and increased infection risk, which complicate their clinical management. The review also discusses emerging treatment strategies aimed at minimizing steroid dependence, including combination therapies with disease-modifying agents and biologics. By examining the nuanced balance between the therapeutic benefits and potential risks of corticosteroids, this review aims to inform future research and clinical practices in the management of autoimmune disorders. Keywords: Corticosteroids, autoimmune disorders, rheumatoid arthritis, systemic lupus erythematosus, asthma

The Relevance and Implications of Monoclonal Antibody Therapies on Traumatic Brain Injury Pathologies.

Traumatic brain injury (TBI) is a global public health concern. It remains one of the leading causes of morbidity and mortality. TBI pathology involves complex secondary injury cascades that are associated with cellular and molecular dysfunction, including oxidative stress, coagulopathy, neuroinflammation, neurodegeneration, neurotoxicity, and blood-brain barrier (BBB) dysfunction, among others. These pathological processes manifest as a diverse array of clinical impairments. They serve as targets for potential therapeutic intervention not only in TBI but also in other diseases. Monoclonal antibodies (mAbs) have been used as key therapeutic agents targeting these mechanisms for the treatment of diverse diseases, including neurological diseases such as Alzheimer's disease (AD). MAb therapies provide a tool to block disease pathways with target specificity that may be capable of mitigating the secondary injury cascades following TBI. This article reviews the pathophysiology of TBI and the molecular mechanisms of action of mAbs that target these shared pathological pathways in a wide range of diseases. Publicly available databases for various applications of mAb therapy were searched and further classified to assess relevance to TBI pathology and evaluate current stages of development. The authors intend for this review to highlight the potential impact of current mAb technology within pathological TBI processes.

Exploring bacterial key genes and therapeutic agents for breast cancer among the Ghanaian female population: Insights from In Silico analyses.

Breast cancer (BC) is yet a significant global health challenge across various populations including Ghana, though several studies on host-genome associated with BC have been investigated molecular mechanisms of BC development and progression, and candidate therapeutic agents. However, a little attention has been given on microbial genome in this regard, although alterations in microbiota and epigenetic modifications are recognized as substantial risk factors for BC. This study focused on identifying bacterial key genes (bKGs) associated with BC infections in the Ghanaian population and exploring potential drug molecules by targeting these bKGs through in silico analyses. At first, 16S rRNA bacterial sequence data were downloaded from NCBI database comprising 520 samples from BC patients and 442 from healthy controls. Analysis of 16S rRNA-Seq data showed significant differences in bacterial abundance between BC and healthy groups and identified 26 differential genera with the threshold values at |log2FC|>2.0 and p-value≤0.05. It was observed that two genera Prevotella and Anaerovibria are significantly upregulated in BC patients and others are downregulated. Functional analysis based on all differential genera identified 19 MetaCyc signaling pathways, twelve of which were significantly enriched in BC patients by containing 165 genes Top-ranked 10 genes mdh, pykF, gapA, zwf, pgi, tpiA, pgk, pfkA, ppsA, and pykA were identified as BC-causing bacterial key genes (bKGs) through protein-protein interaction network analysis. Subsequently, the bKG-guided top ranked 10 drug molecules Digitoxin, Digoxin, Ledipasvir, Suramin, Ergotamine, Venetoclax, Nilotinib, Conivaptan, Dihydroergotamine, and Elbasvir were identified using molecular docking analysis. The stability of top-ranked three drug-target complexes (Digitoxin-pykA, Digoxin-mdh, and Ledipasvir-pgi) were confirmed through the molecular dynamics simulation studies. Therefore, these findings might be useful resources to the wet-lab researchers for further experimental validation on bacterial therapies against BC.

Bioinformatics analysis of key genes and potential therapeutic agents for vascular calcification in chronic kidney disease

Vascular calcification is a common complication of chronic kidney disease (CKD). The molecular mechanisms underlying this condition and the efficacy of potential treatments remain unclear. Bioinformatic methods were employed to analyze gene ontology (GO) annotations and pathway enrichments. Subsequently, an analysis of potential therapeutic agents for vascular calcification in CKD was performed. A total of 76 common genes, 181 enriched GO annotations—comprising 153 biological processes, 10 cellular components, and 18 molecular functions—41 KEGG pathways, 13 REACTOME pathways, and 3 BIOCARTA pathways were identified. Five key genes (PSMC5, TNFSF11, TNFRSF11A, TNFRSF12A, and ICAM1) were isolated. Most notably, the top five potential therapeutic drugs—ENAVATUZUMAB, DENOSUMAB, ALICAFORSEN, BI-505, and ENLIMOMAB PEGOL—were identified for vascular calcification in CKD. However, further molecular biological experiments are required to confirm these findings.

What's New in Ocular Drug Delivery: Advances in Suprachoroidal Injection since 2023.

Despite significant advancements in ocular drug delivery, challenges persist in treating posterior segment diseases like macular edema (ME) and age-related macular degeneration (AMD). Suprachoroidal (SC) injections are a promising new method for targeted drug delivery to the posterior segment of the eye, providing direct access to the choroid and retina while minimizing systemic exposure and side effects. This review examines the anatomical and physiological foundations of the SC space; evaluates delivery devices such as microcatheters, hypodermic needles, and microneedles; and discusses pharmacokinetic principles. Additionally, advancements in gene delivery through SC injections are explored, emphasizing their potential to transform ocular disease management. This review also highlights clinical applications in treating macular edema, diabetic macular edema, age-related macular degeneration, choroidal melanoma, and glaucoma. Overall, SC injections are emerging as a promising novel route for administering ophthalmic treatments, with high bioavailability, reduced systemic exposure, and favorable safety profiles. Key therapeutic agents such as triamcinolone acetonide, dexamethasone, AAV-based gene therapy, and axitinib have shown promise. The field of suprachoroidal injection is progressing rapidly, and this review article, while attempting to encapsulate most of the published preclinical and clinical studies, mainly focuses on those that are published within 2023 and 2024.

Targeted Therapies for EGFR Exon 20 Insertion Mutation in Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) frequently harbors mutations in the epidermal growth factor receptor (EGFR), with exon 20 insertions comprising 1-10% of these mutations. EGFR exon 20 insertions are less responsive to conventional tyrosine kinase inhibitors (TKIs), leading to the development of targeted agents. This review explores key therapeutic agents, such as Amivantamab, Mobocertinib, Poziotinib, Zipalertinib, and Sunvozertinib, which have shown promise in treating NSCLC with EGFR exon 20 insertions. Amivantamab, a bispecific antibody-targeting EGFR and c-MET, demonstrates significant efficacy, particularly when combined with chemotherapy. Mobocertinib, a TKI, selectively targets EGFR exon 20 mutations but faces limitations in efficacy. Poziotinib, another oral TKI, shows mixed results due to mutation-specific responses. Zipalertinib and Sunvozertinib have emerged as potent TKIs with promising clinical data. Despite these advances, challenges in overcoming resistance mutations and improving central nervous system penetration remain. Future research should focus on optimizing first-line combination therapies and enhancing diagnostic strategies for comprehensive mutation profiling.

Epidemiological trends in serotypes distribution and antimicrobial resistance in Salmonella from humans in Taiwan, 2004-2022

ObjectivesSalmonella, a zoonotic pathogen, significantly impacts global human health. Understanding its serotype distribution and antimicrobial resistance is crucial for effective control measures and medical interventions. MethodsWe collected Salmonella isolates and demographic data from Taiwanese hospitals between 2004 and 2022, analyzing their serotypes and antimicrobial susceptibility. ResultsAmong 40,595 isolates, salmonellosis predominated in children aged 0-4 (61.2%) years and among males (55.2%). Males also showed higher rates of extraintestinal infections (18.1% vs 16.0%, P <0.001), particularly, in the ≥65 years age group (52.4%). The top five serovars were S. Enteritidis (32.8%), S. Typhimurium (21.7%), S. Newport (6.2%), S. Stanley (4.7%), and S. Anatum (4.0%). Notably, S. Enteritidis prevalence increased from 23.9% (2004-2005) to 43.6% (2021-2022). Antimicrobial resistance was high, with a 51.6% multidrug resistance (MDR) rate. Disturbingly, MDR rates exceeded 90% in serovars Albany, Schwarzengrund, Choleraesuis, and Goldcoast. Resistance to key therapeutic agents, azithromycin, cefotaxime, and ciprofloxacin, exhibited concerning upward trends, and the surge in cefotaxime and ciprofloxacin resistance was closely linked to the emergence and spread of MDR S. Anatum and S. Goldcoast clones. ConclusionsPrioritizing control measures against S. Enteritidis and closely monitoring the prevalence and spread of MDR clones are imperative to mitigate Salmonella infections in Taiwan.

Sequential activation of E2F via Rb degradation and c-Myc drives resistance to CDK4/6 inhibitors in breast cancer

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are key therapeutic agents in the management of metastatic hormone-receptor-positive breast cancer. However, the emergence of drug resistance limits their long-term efficacy. Here, we show that breast cancer cells develop CDK4/6i resistance via a sequential two-step process of E2F activation. This process entails retinoblastoma (Rb)-protein degradation, followed by c-Myc-mediated amplification of E2F transcriptional activity. CDK4/6i treatment halts cell proliferation in an Rb-dependent manner but dramatically reduces Rb-protein levels. However, this reduction in Rb levels insufficiently induces E2F activity. To develop CDK4/6i resistance, upregulation or activating mutations in mitogenic or hormone signaling are required to stabilize c-Myc levels, thereby augmenting E2F activity. Our analysis of pre-treatment tumor samples reveals a strong correlation between c-Myc levels, rather than Rb levels, and poor therapeutic outcomes after CDK4/6i treatment. Moreover, we propose that proteasome inhibitors can potentially reverse CDK4/6i resistance by restoring Rb levels.

BMP-6 promotes type 2 immune response during enhancement of rat mandibular bone defect healing.

Bone morphogenetic proteins (BMPs) are used as key therapeutic agents for the treatment of difficult fractures. While their effects on osteoprogenitors are known, little is known about their effects on the immune system. We used permutations of BMP-6 (B), vascular endothelial growth factor (V), and Hedgehog signaling pathway activator smoothened agonist (S), to treat a rat mandibular defect and investigated healing outcomes at week 8, in correlation with the cellular landscape of the immune cells in the fracture callus at week 2. Maximum recruitment of immune cells to the fracture callus is known to occur at week 2. While the control, S, V, and VS groups remained as nonunions at week 8; all BMP-6 containing groups - B, BV, BS and BVS, showed near-complete to complete healing. This healing pattern was strongly associated with significantly higher ratios of CD4 T (CD45+CD3+CD4+) to putative CD8 T cells (CD45+CD3+CD4-), in groups treated with any permutation of BMP-6. Although, the numbers of putative M1 macrophages (CD45+CD3-CD11b/c+CD38high) were significantly lower in BMP-6 containing groups in comparison with S and VS groups, percentages of putative - Th1 cells or M1 macrophages (CD45+CD4+IFN-γ+) and putative - NK, NKT or cytotoxic CD8T cells (CD45+CD4-IFN-γ+) were similar in control and all treatment groups. Further interrogation revealed that the BMP-6 treatment promoted type 2 immune response by significantly increasing the numbers of CD45+CD3-CD11b/c+CD38low putative M2 macrophages, putative - Th2 cells or M2 macrophages (CD45+CD4+IL-4+) cells and putative - mast cells, eosinophils or basophils (CD45+CD4-IL-4+ cells). CD45- non-haematopoietic fractions of cells which encompass all known osteoprogenitor stem cells populations, were similar in control and treatment groups. This study uncovers previously unidentified regulatory functions of BMP-6 and shows that BMP-6 enhances fracture healing by not only acting on osteoprogenitor stem cells but also by promoting type 2 immune response.

Analysis and identification of potential type II helper T cell (Th2)-Related key genes and therapeutic agents for COVID-19

COVID-19 pandemic poses a severe threat to public health. However, so far, there are no effective drugs for COVID-19. Transcriptomic changes and key genes related to Th2 cells in COVID-19 have not been reported. These genes play an important role in host interactions with SARS-COV-2 and may be used as promising target. We analyzed five COVID-19-associated GEO datasets (GSE157103, GSE152641, GSE171110, GSE152418, and GSE179627) using the xCell algorithm and weighted gene co-expression network analysis (WGCNA). Results showed that 5 closely correlated modular genes to COVID-19 and Th2 cell enrichment levels, including purple, blue, pink, tan and turquoise, were intersected with differentially expressed genes (DEGs) and 648 shared genes were obtained. GO and KEGG pathway enrichment analyses revealed that they were enriched in cell proliferation, differentiation, and immune responses after virus infection. The most significantly enriched pathway involved the regulation of viral life cycle. Three key genes, namely CCNB1, BUB1, and UBE2C, may clarify the pathogenesis of COVID-19 associated with Th2 cells. 11 drug candidates were identified that could down-regulate three key genes using the cMAP database and demonstrated strong drugs binding energies aganist the three keygenes using molecular docking methods. BUB1, CCNB1 and UBE2C were identified key genes for COVID-19 and could be promising therapeutic targets.

Evaluating Opicapone as Add-on Treatment to Levodopa/DDCI in Patients with Parkinson's Disease.

COMT (catechol-O-methyltransferase) inhibitors are key therapeutic agents in the management of motor fluctuations (MF) in patients with Parkinson’s disease (PD). As levodopa/DDCI add-on therapy, their main benefit lies in increasing ON-time and reducing OFF-time for PD patients in the middle stages of the disease. Two of the three available COMT inhibitors, tolcapone and entacapone, have been approved for over two decades.Opicapone, a third-generation COMT inhibitor approved in 2016, was designed with the aim of overcoming specific challenges of the earlier generation compounds, specifically hepatotoxicity and short effect duration. This review aims at highlighting the specific properties and characteristics of opicapone, namely combining efficacy with good tolerability as demonstrated in the registration studies and since then confirmed under real-world conditions. Opicapone has been shown to be effective in patients with early, as well as late motor fluctuations. Whilst patients in the earlier Hoehn and Yahr stages benefit more than patients in later stages, the incidence of dyskinesia in patients with recent onset MF is around half that of patients with more established fluctuations. With the added advantage of a once-daily administration, this particular COMT inhibitor provides a simple, yet effective therapy for patients with Parkinson’s disease and MF.

Biomarker discovery for practice of precision medicine in hypopharyngeal cancer: a theranostic study on response prediction of the key therapeutic agents

BackgroundHypopharyngeal cancer is a relatively rare malignancy with poor prognosis. Current chemotherapeutic algorithm is still far from personalized medicine, and the identification of the truly active therapeutic biomarkers and/or targets is eagerly awaited.MethodsVenturing to focus on the conventional key chemotherapeutic drugs, we identified the most correlative genes (and/or proteins) with cellular sensitivity to docetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-FU) in the expression levels, through 3 steps approach: genome-wide screening, confirmation study on the quantified expression levels, and knock-down and transfection analyses of the candidates. The probable action pathways of selected genes were examined by Ingenuity Pathway Analysis using a large-scale database, The Cancer Genome Atlas.ResultsThe first genome-wide screening study derived 16 highly correlative genes with cellular drug sensitivity in 15 cell lines (|R| > 0.8, P < 0.01 for CDDP and 5-FU; |R| > 0.5, P < 0.05 for TXT). Among 10 genes the observed correlations were confirmed in the quantified gene expression levels, and finally knock-down and transfection analyses provided 4 molecules as the most potent predictive markers-AGR2 (anterior gradient 2 homolog gene), and PDE4D (phosphodiesterase 4D, cAMP-specific gene) for TXT; NINJ2 (nerve Injury-induced protein 2); CDC25B (cell division cycle 25 homolog B gene) for 5-FU- in both gene and protein expression levels. Overexpression of AGR2, PDE4D signified worse response to TXT, and the repressed expression sensitized TXT activity. Contrary to the findings, in the other 2 molecules, NINJ2 and CDC25, there observed opposite relationship to cellular drug response to the relevant drugs. IPA raised the potential that each selected molecule functionally interacts with main action pathway (and/or targets) of the relevant drug such as tubulin β chain genes for TXT, DNA replication pathway for CDDP, and DNA synthesis pathway and thymidylate synthetase gene for 5-FU.ConclusionWe newly propose 4 molecules -AGR2, PDE4D,NINJ2 and CDC25B) as the powerful exploratory markers for prediction of cellular response to 3 key chemotherapeutic drugs in hypopharyngeal cancers and also suggest their potentials to be the therapeutic targets, which could contribute to the development of precision medicine of the essential chemotherapy in hypopharyngeal patients. (339 words).

Cytotoxic effect, enzyme inhibition, and in silico studies of some novel N-substituted sulfonyl amides incorporating 1,3,4-oxadiazol structural motif.

The acetylcholinesterase and carbonic anhydrase inhibitors (AChEIs and hCAIs) remain key therapeutic agents for many bioactivities such as anti-Alzheimer and antiobesity antiepileptic, anticancer, antiinfective, antiglaucoma, and diuretic effects. Here, it has been attempted to discover novel multi-target AChEIs and hCAIs that are highly potent, orally bioavailable, may be brain penetrant, and have higher effectiveness at lower doses than tacrine and acetazolamide. After detailed investigations both in vitro and in silico, novel N-substituted sulfonyl amide derivatives (6a–j) were determined to be highly potent inhibitors for AChE and hCAs (KIs are in the range of 23.11–52.49 nM, 18.66–59.62 nM, and 9.33–120.80 nM for AChE, hCA I, and hCA II, respectively). Moreover, according to the cytotoxic effect studies, such as the ADME-Tox, cortex neuron cells, and neuroblastoma SH-SY5Y cell line, compounds 6a, 6d, and 6h, which are the most potent representative versus the target enzymes, were identified as orally bioavailable, highly selective, and brain preferentially distributed AChEIs and hCAIs. The docking studies revealed precise binding modes between 6a, 6d, and 6h and hCA II, hCA I, and AChE, respectively. The results presented here might provide a solid basis for further investigation into more potent AChEIs and hCAIs.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s11030-022-10422-8.

Clinical Pharmacist's Intervention to Improve Medication Titration for Heart Failure: First Experience from Sudan.

BackgroundMedications known to improve outcomes in heart failure (HF) are either not prescribed or prescribed at sub-therapeutic doses. The addition of clinical pharmacists to the HF team positively impacts optimizing prognostic medications for a patient with HF with reduced ejection fraction (HFrEF).ObjectiveTo assess the intervention of the clinical pharmacist as part of the multidisciplinary (MD) team in up-titration to achieve target doses of key therapeutic agents for HFrEF.MethodsThis was a prospective one group pretest-posttest interventional study; a comparison of the target dose achievement of key therapeutic agents for HFrEF was performed before and after clinical pharmacist interventions.ResultsOut of 110 HFrEF patients, 57.3% were males, and the mean age of patients was 55.8 years (SD 12.6). Cardiomyopathy was the leading cause of HF. At baseline, 86% were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (ACEIs/ARBs/ARNi) and 93.6% on beta blockers (BBs). At the end of study, the proportion of patients achieved the target dose was significantly increased (0 vs 77.4%, 6.8 vs 85.4%, and 0 vs 55.6%) for ACEIs, ARBs and ARNi, respectively, and (8.6% vs 66.1%; P = 0.001) for BBs. Moreover, the up-titration process was associated with significant improvement in most clinical as ejection fraction and New York Heart Association (NYHA) scale and laboratory characteristics.ConclusionAs a part of the MD team in the outpatient HF clinic, the clinical pharmacists increased the percentage of HFrEF patients achieving the target or maximal doses of key therapeutic agents and improving clinical and laboratory parameters.

Identifying key genes and screening therapeutic agents associated with diabetes mellitus and HCV-related hepatocellular carcinoma by bioinformatics analysis

Incidence of both Type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC) are rapidly increasing worldwide. One of the leading causes of HCC is hepatitis C virus (HCV), which is a resource of blood-borne viral infection. HCV increases the risk for HCC probably by promoting fibrosis and cirrhosis. Association among T2DM and HCV related HCC remains significant, indicating that such association is clinically reliable and robust. Lawson was the first who uncovered HCC in person suffered from T2DM. Until now, genetic association between HCV related HCC and T2DM is poorly known. Current work was designed to figure out the molecular mechanisms of both diseases by identifying the hub genes and therapeutic drugs using integrated bioinformatics analysis. Four microarray datasets were downloaded from GEO database and analyzed using R in order to obtain different expressed genes (DEGs). Protein-protein interaction (PPI) networks was constructed using STRING tool and visualized by Cytoscape. Moreover, hub genes were identified on the basis of their degree of connectivity. Finally, Networkanalyst and DGIdb were used for the identification of transcription factors (TFs) and selection of candidate drugs, respectively. A total of 53 DEGs were identified, of which 41 were upregulated genes and 12 were downregulated genes. PPI network obtained from STRING were subjected to Cytoscape plugin cytoHubba, and top 10 genes (AURKA, JUN, AR, MELK, NCOA2, CENPF, NCAPG, PCK1, RAD51AP1, and GTSE1) were chosen as the target hub genes based on the highest degree of connectivity. Furthermore, 47 drugs of AURKA, JUN, AR, MELK, and NCOA2 were found having therapeutic potential to treat HCV-HCC in patients with T2DM. This study updates the information and yield a new perspective in context of understanding the pathogenesis and development of HCV related HCC in affected persons with T2DM. In vivoandin vitroinvestigation of hub genes and pathway interaction is essential to delineate the specific roles of the novel hub genes, which may help to reveal the genetic association between HCV-HCC and T2DM. In future, hub genes along with their candidate drugs might be capable of improving the personalized detection and therapies for both diseases.

Monoclonal Antibodies as Neurological Therapeutics.

Over the last 30 years the role of monoclonal antibodies in therapeutics has increased enormously, revolutionizing treatment in most medical specialties, including neurology. Monoclonal antibodies are key therapeutic agents for several neurological conditions with diverse pathophysiological mechanisms, including multiple sclerosis, migraines and neuromuscular disease. In addition, a great number of monoclonal antibodies against several targets are being investigated for many more neurological diseases, which reflects our advances in understanding the pathogenesis of these diseases. Untangling the molecular mechanisms of disease allows monoclonal antibodies to block disease pathways accurately and efficiently with exceptional target specificity, minimizing non-specific effects. On the other hand, accumulating experience shows that monoclonal antibodies may carry class-specific and target-associated risks. This article provides an overview of different types of monoclonal antibodies and their characteristics and reviews monoclonal antibodies currently in use or under development for neurological disease.

Comprehensive analysis of key biomarkers, immune infiltration and potential therapeutic agents for ulcerative colitis

AimsThere has been an increasing trend towards the ulcerative colitis (UC) incidence worldwide. The present study aimed to explore novel biomarkers and potential therapeutic agents for UC. Materials and methodsDifferentially expressed genes (DEGs) among UC and healthy control samples were identified by GEO2R online tool. Functional analysis was performed and protein-protein interaction networks were constructed. The hub genes were explored by Cytoscape, and quantitative real-time-PCR (qRT-PCR) was used to valid their expression in clinical samples. ImmuCellAI was utilized to analyze the fraction of 24 types of immune cells. The L1000 platform was applied to determine potential agents for UC treatment. The dextran sulfate sodium (DSS)-induced colitis model was used to identify the therapeutic effect of meclofenamic acid. Key findingsA total of 270 DEGs were identified among UC and healthy control samples. Functional analysis indicated that the DEGs were primarily enriched in several immune response and digestion pathways. A proportion of 18 immune-cell types was found to be significantly altered between UC and healthy control samples. 10 compounds were predicted to have therapeutic potentials for treating UC. Among them, we selected meclofenamic acid to identify its therapeutic effect on UC treatment by animal experiments. SignificanceThe current study comprehensively analyzed the DEGs and immune infiltration in UC, as well as screened for potential agents for UC treatment.

COVID-19 – Does This Disease Kill Due to Imbalance of the Renin Angiotensin System (RAS) Caused by Genetic and Gender Differences in the Response to Viral ACE 2 Attack?

Debate continues in the medical literature on the role of the renin angiotensin system (RAS) in Coronavirus disease 2019 (COVID-19) pathophysiology and the implications for the use of cardiovascular drugs acting on the RAS. Could these drugs – which include angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptors blockers (ARBs) – be harmful or potential key therapeutic agents in COVID-19? And, could potentially helpful measures be available and in plain view on the pharmacy shelf?

Identification of key genes, pathways and potential therapeutic agents for IgA nephropathy using an integrated bioinformatics analysis.

Purpose:This study aims to identify immunoglobulin-A-nephropathy-related genes based on microarray data and to investigate novel potential gene targets for immunoglobulin-A-nephropathy treatment.Methods:Immunoglobulin-A-nephropathy chip data was obtained from the Gene Expression Omnibus database, which included 10 immunoglobulin-A-nephropathy and 22 normal samples. We used the limma package of R software to screen differentially expressed genes in immunoglobulin-A-nephropathy and normal glomerular compartment tissues. Functional enrichment (including cellular components, molecular functions, biological processes) and signal pathways were performed for the differentially expressed genes. The online analysis database (STRING) was used to construct the protein-protein interaction networks of differentially expressed genes, and Cytoscape software was used to identify the hub genes of the signal pathway. In addition, we used the Connectivity Map database to predict possible drugs for the treatment of immunoglobulin-A-nephropathy.Results:A total of 348 differentially expressed genes were screened including 107 up-regulated and 241 down-regulated genes. Functional analysis showed that up-regulated differentially expressed genes were mainly concentrated on leukocyte migration, and the down-regulated differentially expressed genes were significantly enriched in alpha-amino acid metabolic process. A total of six hub genes were obtained: JUN, C3AR1, FN1, AGT, FOS, and SUCNR1. The small-molecule drugs thapsigargin, ciclopirox and ikarugamycin were predicted therapeutic targets against immunoglobulin-A-nephropathy.Conclusion:Differentially expressed genes and hub genes can contribute to understanding the molecular mechanism of immunoglobulin-A-nephropathy and providing potential therapeutic targets and drugs for the diagnosis and treatment of immunoglobulin-A-nephropathy.