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Frontiers in Cellular and Infection... 2023The coronavirus disease 2019 (COVID-19) pandemic, stemming from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has persistently threatened the global...
INTRODUCTION
The coronavirus disease 2019 (COVID-19) pandemic, stemming from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has persistently threatened the global health system. Meanwhile, tuberculosis (TB) caused by () still continues to be endemic in various regions of the world. There is a certain degree of similarity between the clinical features of COVID-19 and TB, but the underlying common pathogenetic processes between COVID-19 and TB are not well understood.
METHODS
To elucidate the common pathogenetic processes between COVID-19 and TB, we implemented bioinformatics and systematic research to obtain shared pathways and molecular biomarkers. Here, the RNA-seq datasets (GSE196822 and GSE126614) are used to extract shared differentially expressed genes (DEGs) of COVID-19 and TB. The common DEGs were used to identify common pathways, hub genes, transcriptional regulatory networks, and potential drugs.
RESULTS
A total of 96 common DEGs were selected for subsequent analyses. Functional enrichment analyses showed that viral genome replication and immune-related pathways collectively contributed to the development and progression of TB and COVID-19. Based on the protein-protein interaction (PPI) network analysis, we identified 10 hub genes, including IFI44L, ISG15, MX1, IFI44, OASL, RSAD2, GBP1, OAS1, IFI6, and HERC5. Subsequently, the transcription factor (TF)-gene interaction and microRNA (miRNA)-gene coregulatory network identified 61 TFs and 29 miRNAs. Notably, we identified 10 potential drugs to treat TB and COVID-19, namely suloctidil, prenylamine, acetohexamide, terfenadine, prochlorperazine, 3'-azido-3'-deoxythymidine, chlorophyllin, etoposide, clioquinol, and propofol.
CONCLUSION
This research provides novel strategies and valuable references for the treatment of tuberculosis and COVID-19.
Topics: Humans; COVID-19; SARS-CoV-2; Computational Biology; Genes, Regulator; Tuberculosis; Mycobacterium tuberculosis; Gene Expression Profiling; MicroRNAs
PubMed: 38162574
DOI: 10.3389/fcimb.2023.1280223 -
PloS One 2023Co-existence of life style disorders, like, Diabetes or Hypertension, increases risk of, treatment failure, deaths and developing drug-resistant TB. Concomitant...
Co-existence of life style disorders, like, Diabetes or Hypertension, increases risk of, treatment failure, deaths and developing drug-resistant TB. Concomitant administration of drugs to treat dual/multi-morbidities may alter their effectiveness, in additive/synergistic or adverse/antagonistic manner. We evaluated interactive effect of 7 anti-hyperglycaemic (HG) and 6 anti-hypertensive (HT) drugs on the inhibitory (MICs) and bactericidal (% killing of intracellular bacilli) activities of anti-TB drugs, Isoniazid (INH), Rifampicin (RFM), Ethambutol (EMB) and Streptomycin (STR) against M. tuberculosis. Five anti-HG drugs, namely, Acarbose, Acetohexamide, Glyburide, Repaglinide and Sitagliptin imparted either 'additive' or 'no effect' on the activities (inhibition or % killing) of all the four anti-TB drugs, as evident by their lower FICs (Fractional Inhibitory concentrations) and higher bacterial killing in combination. Metformin and Rosiglitazone, however, exerted adverse effect on the Ethambutol (FICs >2.0). All the six anti-HT drugs, namely, Atenolol, Hydrochlorothiazide, Ramipril, Valsartan, Nifedipine and Verapamil exerted either 'additive'/'synergistic' or 'no effect' on the activities of anti-TB drugs. These findings may help clinicians to select safe and helpful anti-HG or anti-HT drugs for TB patients, if, suffering with diabetes or hypertension like co-morbidities and receiving DOTs (a set regimen for the treatment of TB based on the WHO guidelines).
Topics: Humans; Antitubercular Agents; Antihypertensive Agents; Ethambutol; Pharmaceutical Preparations; Mycobacterium tuberculosis; Isoniazid; Microbial Sensitivity Tests; Tuberculosis; Hypertension; Diabetes Mellitus; Hypoglycemic Agents; Tuberculosis, Multidrug-Resistant
PubMed: 38032920
DOI: 10.1371/journal.pone.0292397 -
European Review For Medical and... Jun 2023As the prevalence of diabetes rises, the use of antidiabetic drugs becomes more frequent. Thus, focusing on the effects of these drugs on water-sodium balance and... (Review)
Review
As the prevalence of diabetes rises, the use of antidiabetic drugs becomes more frequent. Thus, focusing on the effects of these drugs on water-sodium balance and electrolyte regulation is necessary. This review discusses the effects and the mechanisms behind them. Several sulfonylureas, such as chlorpropamide, methanesulfonamide, and tolbutamide, exhibit water-retaining properties. Other sulfonylureas, such as glipizide, glibenclamide, acetohexamide, and tolazamide, are not antidiuretic or even diuretic. Numerous clinical studies showed that metformin can reduce serum magnesium concentrations and may have an effect on the cardiovascular system, but the specific mechanism remains to be discussed. Different opinions exist about the mechanisms of thiazolidinedione-induced fluid retention. Sodium-glucose cotransporter 2 inhibitors can cause osmotic diuresis and natriuresis and elevated serum potassium and magnesium concentrations. Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors can enhance urine sodium excretion. At the same time, increased urinary sodium caused by sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors reduce blood pressure and plasma volume, thereby protecting the heart. Insulin has a sodium-retaining effect and is also associated with hypokalemia, hypomagnesemia, and hypophosphatemia. Several of the aforementioned pathophysiological changes and mechanisms have been discussed, and conclusions have been drawn. However, further investigation and discussion are still warranted.
Topics: Humans; Hypoglycemic Agents; Sodium; Magnesium; Sulfonylurea Compounds; Dipeptidyl-Peptidase IV Inhibitors; Electrolytes; Glucose; Water; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Diabetes Mellitus, Type 2
PubMed: 37401315
DOI: 10.26355/eurrev_202306_32817 -
BioMed Research International 2022Lupus nephritis (LN) is the most common and significant complication of systemic lupus erythematosus (SLE) due to its poor prognosis and mortality rates in SLE patients....
Lupus nephritis (LN) is the most common and significant complication of systemic lupus erythematosus (SLE) due to its poor prognosis and mortality rates in SLE patients. There is a critical need for new drugs as the pathogenesis of LN remains to be elucidated and immunosuppressive therapy comes with many deficiencies. In this study, 23 hub genes (IFI6, PLSCR1, XAF1, IFI16, IFI44, MX1, IFI44L, IFIT3, IFIT2, IFI27, DDX58, EIF2AK2, IFITM1, RTP4, IFITM3, TRIM22, PARP12, IFIH1, OAS1, HERC6, RSAD2, DDX60, and MX2) were identified through bioinformatics and network analysis and are closely related to interferon production and function. Interestingly, immune cell infiltration analysis and correlation analysis demonstrate a positive correlation between the expression of 23 hub genes and monocyte infiltration in glomeruli and M2 macrophage infiltration in the tubulointerstitium of LN patients. Additionally, the CTD database, DsigDB database, and DREIMT database were used to explore the bridging role of genes in chemicals and LN as well as the potential influence of these chemicals on immune cells. After comparison and discussion, six small molecules (Acetohexamide, Suloctidil, Terfenadine, Prochlorperazine, Mefloquine, and Triprolidine) were selected for their potential ability in treating lupus nephritis.
Topics: Computational Biology; Female; Gene Expression; Genes, Regulator; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Membrane Proteins; RNA-Binding Proteins
PubMed: 35502341
DOI: 10.1155/2022/2259164 -
Indian Journal of Dermatology 2021Xeroderma pigmentosum (XP) is an autosomal recessive genetic disease caused by a defect in the DNA repair system, exhibiting skin cancer on sun exposure. As it is an... (Review)
Review
Xeroderma pigmentosum (XP) is an autosomal recessive genetic disease caused by a defect in the DNA repair system, exhibiting skin cancer on sun exposure. As it is an incurable disease, therapeutic strategies of this disease are critical. This review article takes an attempt to explore the current therapeutic advancements in XP. Different approaches including sun avoidance; surgical removal of cancerous lesions; laser and photodynamic therapy; use of retinoid, 5-fluorouracil, imiquimod, photolyase, and antioxidant; interferon therapy and gene therapy are chosen by doctors and patients to lessen the adverse effects of this disease. Among these options, sun avoidance, use of 5-fluorouracil and imiquimod, and interferon therapy are effective. However, some approaches including laser and photodynamic therapy, and the use of retinoids are effective against skin cancer having severe side effects. Furthermore, surgical removal of cancerous lesions and use of antioxidants are considered to be effective against this disease; however, efficacies of these are not experimentally determined. In addition, some approaches including oral vismodegib, immunotherapy, nicotinamide, acetohexamide, glimepiride-restricted diet are found to be effective to minimize the complications secondary to defects in the nucleotide excision repair (NER) system and also enhance the NER, which are under experimental level yet. Besides these, gene therapy, including the introduction of missing genes and genome edition, may be a promising approach to combat this disease, which is also not well established now. In the near future, these approaches may be effective tools to manage XP.
PubMed: 35283513
DOI: 10.4103/ijd.ijd_329_21 -
BioMed Research International 2022We aim to identify the common genes, biological pathways, and treatment targets for primary Sjögren's syndrome patients with varying degrees of fatigue features. We...
We aim to identify the common genes, biological pathways, and treatment targets for primary Sjögren's syndrome patients with varying degrees of fatigue features. We select datasets about transcriptomic analyses of primary Sjögren's syndrome (pSS) patients with different degrees of fatigue features and normal controls in peripheral blood. We identify common differentially expressed genes (DEGs) to find shared pathways and treatment targets for pSS patients with fatigue and design a protein-protein interaction (PPI) network by some practical bioinformatic tools. And hub genes are detected based on the PPI network. We perform biological pathway analysis of common genes by Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Lastly, potential treatment targets for pSS patients with fatigue are found by the Enrichr platform. We discovered that 27 DEGs are identified in pSS patients with fatigue features and the severe fatigued pSS-specific gene is RTP4. DEGs are mainly localized in the mitochondria, endosomes, endoplasmic reticulum, and cytoplasm and are involved in the biological process by which interferon acts on cells and cells defend themselves against viruses. Molecular functions mainly involve the process of RNA synthesis. The DEGs of pSS are involved in the signaling pathways of viruses such as hepatitis C, influenza A, measles, and EBV. Acetohexamide PC3 UP, suloctidil HL60 UP, prenylamine HL60 UP, and chlorophyllin CTD 00000324 are the four most polygenic drug molecules. PSS patients with fatigue features have specific gene regulation, and chlorophyllin may alleviate fatigue symptoms in pSS patients.
Topics: Biomarkers; Computational Biology; Fatigue; Gene Expression Profiling; Humans; Sjogren's Syndrome
PubMed: 35075430
DOI: 10.1155/2022/7697558 -
European Journal of Pharmaceutical... May 2021Cell surface binding immunoglobin protein (csBiP) is predicted to be susceptible to SARS-CoV-2 binding. With a substrate-binding domain (SBD) that binds to polypeptides...
AIMS
Cell surface binding immunoglobin protein (csBiP) is predicted to be susceptible to SARS-CoV-2 binding. With a substrate-binding domain (SBD) that binds to polypeptides and a nucleotide-binding domain (NBD) that can initiate extrinsic caspase-dependent apoptosis, csBiP may be a promising therapeutic target for COVID-19. This study aims to identify FDA-approved drugs that can neutralize viral binding and prevent viral replication by targeting the functional domains of csBiP.
METHODS
In silico screening of 1999 FDA-approved drugs against the functional domains of BiP were performed using three molecular docking programs to avoid bias from individual docking programs. Top ligands were selected by averaging the ligand rankings from three programs. Interactions between top ligands and functional domains of BiP were analyzed.
KEY FINDINGS
The top 10 SBD-binding candidates are velpatasvir, irinotecan, netupitant, lapatinib, doramectin, conivaptan, fenoverine, duvelisib, irbesartan, and pazopanib. The top 10 NBD-binding candidates are nilotinib, eltrombopag, grapiprant, topotecan, acetohexamide, vemurafenib, paritaprevir, pixantrone, azosemide, and piperaquine-phosphate. Among them, Velpatasvir and paritaprevir are antiviral agents that target the protease of hepatitis C virus. Netupitant is an anti-inflammatory drug that inhibits neurokinin-1 receptor, which contributes to acute inflammation. Grapiprant is an anti-inflammatory drug that inhibits the prostaglandin E receptor protein subtype 4, which is expressed on immune cells and triggers inflammation. These predicted SBD-binding drugs could disrupt SARS-CoV-2 binding to csBiP, and NBD-binding drugs may falter viral attachment and replication by locking the SBD in closed conformation and triggering apoptosis in infected cells.
SIGNIFICANCE
csBiP appears to be a novel therapeutic target against COVID-19 by preventing viral attachment and replication. These identified drugs could be repurposed to treat COVID-19 patients.
Topics: Antiviral Agents; Drug Repositioning; Immunoglobulins; Membrane Proteins; Models, Molecular; Molecular Structure; Protein Conformation; SARS-CoV-2; Structure-Activity Relationship; Virus Attachment; Virus Internalization
PubMed: 33617948
DOI: 10.1016/j.ejps.2021.105771 -
Molecules (Basel, Switzerland) May 2020The interaction of drugs with human serum albumin (HSA) is an important element of therapy. Albumin affects the distribution of the drug substance in the body, as well...
The interaction of drugs with human serum albumin (HSA) is an important element of therapy. Albumin affects the distribution of the drug substance in the body, as well as its pharmacokinetic and pharmacodynamic properties. On the one hand, inflammation and protein glycation, directly associated with many pathological conditions and old age, can cause structural and functional modification of HSA, causing binding disorders. On the other hand, the widespread availability of various dietary supplements that affect the content of fatty acids in the body means that knowledge of the binding activity of transporting proteins, especially in people with chronic diseases, e.g., diabetes, will achieve satisfactory results of the selected therapy. Therefore, the aim of the present study was to evaluate the effect of a mixture of fatty acids (FA) with different saturated and unsaturated acids on the affinity of acetohexamide (AH), a drug with hypoglycaemic activity for glycated albumin, simulating the state of diabetes in the body. Based on fluorescence studies, we can conclude that the presence of both saturated and unsaturated FA disturbs the binding of AH to glycated albumin. Acetohexamide binds more strongly to defatted albumin than to albumin in the presence of fatty acids. The competitive binding of AH and FA to albumin may influence the concentration of free drug fraction and thus its therapeutic effect.
Topics: Acetohexamide; Binding, Competitive; Fatty Acids; Glucose; Glycation End Products, Advanced; Humans; Hypoglycemic Agents; Linoleic Acid; Molecular Dynamics Simulation; Myristic Acid; Oleic Acid; Palmitic Acid; Protein Binding; Protein Conformation; Serum Albumin; Serum Albumin, Human; Solutions; Glycated Serum Albumin
PubMed: 32429512
DOI: 10.3390/molecules25102340 -
Chemical & Pharmaceutical Bulletin 2019Controlling drug crystallization is one of the important issues in pre-formulation study. In recent years, advanced approaches including the use of tailor-made additives... (Review)
Review
Controlling drug crystallization is one of the important issues in pre-formulation study. In recent years, advanced approaches including the use of tailor-made additives have gathered considerable attention to control crystallization behavior of drugs. This review focuses on the use of hydrophilic cyclodextrins (CDs) as additives for controlling drug crystallization. CDs affect the crystallization of drugs in solution and in solid state based on a host-guest interaction. For example, 2,6-di-O-methyl-β-CD and 2-hydroxybutyl-β-CD suppressed solution-mediated transition of drugs during crystallization by the host-guest interaction; as a result, metastable forms selectively precipitated in solution. The use of CDs in crystal engineering provided an opportunity for the detection of a new polymorph by changing the crystallization pathway. It was also possible to modify crystal morphology (i.e., crystal habit) by selective suppression of crystal growth on a certain direction based on the host-gust interaction. For solid formulation, stable amorphous drug/CDs complex under humid conditions was prepared using two different CDs. An overview of some recent progress in the use of CDs in crystal engineering and in amorphous formulation is described in this review.
Topics: Acetohexamide; Aspirin; Crystallization; Drug Compounding; Hydrophobic and Hydrophilic Interactions; Pharmaceutical Preparations; beta-Cyclodextrins
PubMed: 31474729
DOI: 10.1248/cpb.c18-00752