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Sirolimus as a repurposed drug for tendinopathy: A systems biology approach combining computational and experimental methods.

BACKGROUND: Effective drugs for tendinopathy are lacking, resulting in significant morbidity and re-tearing rate after operation. Applying systems biology to identify new applications for current pharmaceuticals can decrease the duration, expenses, and likelihood of failure associated with the development of new drugs. METHODS: We identify tendinopathy signature genes employing a transcriptomics database encompassing 154 clinical tendon samples. We then proposed a systems biology based drug prediction strategy that encompassed multiplex transcriptional drug prediction, systematic review asses

Identification and Evaluation of Besifloxacin as Repurposed Antifungal Drug in Combination With Fluconazole Against Candida albicans.

Emergence of life-threatening fungal infections like systemic candidiasis concurrently with bacterial infections and limitations of current antifungal therapies warrant the discovery of novel inhibitors. We identified besifloxacin (BS), an FDA-approved antibacterial, as a potent antifungal inhibitor. A combination of besifloxacin with fluconazole showed a positive synergy (δ = 29.58) resulting in 80% inhibition of microbial growth. BS was able to reduce the MIC of FLC from 2 mg/L to 0.5 mg/L when used in combination. Additionally, in murine systemic Candida infection, BS reduced fungal load by

Inflammation Targeting and Responsive Multifunctional Drug-Delivery Nanoplatforms for Combined Therapy of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent inflammation, joint swelling, pain, and progressive joint destruction. Methotrexate (MTX) is the standard first-line treatment for RA, but its clinical application is hindered by poor water solubility and non-specific delivery. In this work, a multifunctional drug-delivery nanoplatform that targets both macrophages and tumor necrosis factor α (TNFα) is developed to enhance the therapeutic efficacy of MTX in RA. The nanoplatform consists of folic acid (FA, for macrophage targeting) and a TNFα-specific Aptamer

Vitiligo Signature-Based Drug Screening Identifies Fulvestrant as a Novel Immunotherapy Combination Strategy.

Immunotherapy has revolutionized cancer treatment; however, only 10-30% of patients experience durable survival benefits, while most malignancies remain resistant. In melanoma, vitiligo-like depigmentation is a frequent and generally mild immune-related adverse event, whose presence correlates positively with enhanced antitumor immune responses and prolonged patient survival. By performing comparative analyses between vitiligo and melanoma, we established a biomarker panel-designated the vitiligo signature (VGS)-that differentiates "cold" from "hot" tumors with high accuracy. Leveraging a deep

Advantages and Disadvantages of Drug Combination Treatment: Riluzole, Metformin and Dexamethasone Effect on Glioblastoma Cell.

BACKGROUND/AIM: In glioblastoma multiforme (GBM), a deadly brain tumor, glucose is one of the main fuels for accelerated growth. Patients wi … 2 activation. Disadvantage of Ril+Met treatment was increased cell migration. Taken together, these drug combinations may also allow the reduction of the concentration of Dex to minimize its side effects.

Biomimetic Modification of siRNA/Chemo Drug Nanoassemblies for Targeted Combination Therapy in Breast Cancer.

The development and progression of tumors are characterized by intricate biological processes. Monotherapy not only struggles to achieve effective treatment but also tends to precipitate a series of issues, including multidrug resistance and limited antitumor effect. Consequently, it is imperative to adopt a synergistic multitherapy approach to enhance the efficacy of tumor treatment. The integration of chemotherapy drug with oligonucleotide drug for combinational treatment has shown significant promise in improving tumor therapeutic efficiency. However, the effective in vivo codelivery of oli

Emerging strategy for the treatment of urothelial carcinoma: Advances in antibody-drug conjugates combination therapy.

Urothelial carcinoma (UC) is a prevalent malignant tumor involving the urinary system. Although there are various treatment modalities, including surgery, chemotherapy, and immune checkpoint inhibitor (ICI) therapy, some patients experience disease recurrence and metastasis with poor prognosis and dismal long-term survival. Antibody-drug conjugates (ADCs), which combine the targeting ability of antibody drugs with the cytotoxicity of chemotherapeutic drugs, have recently emerged as a prominent research focus in the development of individualized precision cancer therapy. Although ADCs have impr

Combination of PEGylation and Cationization on Phospholipid-Coated Cyclosporine Nanosuspensions for Enhanced Ocular Drug Delivery.

Strong precorneal clearance mechanisms including reflex blink, constant tear drainage, and rapid mucus turnover constitute great challenges for eye drops for effective drug delivery to the ocular epithelium. In this study, cyclosporine A (CsA) for the treatment of dry eye disease (DED) was selected as the model drug. Two strategies, PEGylation for mucus penetration and cationization for potent cellular uptake, were combined to construct a novel CsA nanosuspension (NS@lipid-PEG/CKC) by coating nanoscale drug particles with a mixture of lipids, DSPE-PEG2000, and a cationic surfactant, cetalkoniu

Nanotechnology-assisted combination drug delivery: a progressive approach for the treatment of acute myeloid leukemia.

Acute myeloid leukemia (AML), a heterogeneous hematopoietic cancer prevalent in adults, has been a leading cause of leukemia-associated deaths for decades. Despite advancements in understanding its pathology and pharmacological targets, therapeutic strategies have seen minimal change. The standard treatment, combining cytarabine and anthracycline, has persisted, accompanied by challenges such as pharmacokinetic issues and non-specific drug delivery, leading to severe side effects. Nanotechnology offers a promising solution through combination drug delivery. FDA-approved CPX351 (VYXEOS™) a lipo

Development of novel dual-target drugs against visceral leishmaniasis and combinational study with miltefosine.

The dual-target inhibitors (ZINC000008876351 and ZINC000253403245) were identified by utilizing an advanced computational drug discovery method by targeting two critical enzymes such as FeSODA (Iron superoxide dismutase) and TryR (Trypanothione reductase) within the antioxidant defense system of Leishmania donovani (Ld). In vitro enzyme inhibition kinetics reveals that both the compound's ability to inhibit the function of enzyme LdFeSODA and LdTryR with inhibition constant (Ki) value in the low μM range. Flow cytometry analysis, specifically at IC50 and 2X IC50 doses of both the compounds, th

Directional atherectomy combined with drug-coated balloon angioplasty for superficial femoral arteriosclerosis obliterans.

INTRODUCTION: This study is an analysis of the therapeutic effects of directional atherectomy combined with drug-coated balloon angioplasty (DA+DCB) in treating superficial femoral arteriosclerosis obliterans. METHODS: Patients in our hospital with superficial femoral arteriosclerosis obliterans who received DA+DCB during the period June 2016 to February 2019 were identified retrospectively. Preoperative demographics, operative details and postoperative follow-up outcomes were analysed statistically. RESULTS: Between June 2016 and February 2019, 48 patients were enrolled in this retrospectiv

Dahuang-Taoren, a botanical drug combination, ameliorates adenomyosis via inhibiting Rho GTPases.

Introduction: Dahuang-Taoren (DT) is a classic combination of botanical drugs applied to treat pain-related diseases in ancient China. Today, DT is frequently applied for dysmenorrhea of adenomyosis (AM) in the clinic. Growing evidence indicates Rho GTPases may play an essential role in AM progression. However, the potential mechanism of DT on Rho GTPases in AM remains unclear. Methods: The expressions of Rho GTPases in the patients with AM were evaluated. Further, pituitary transplantation-induced AM mice and the primary AM endometrial stromal cells (AMESCs) were subjected to DT intervention.

Combined Therapy of Experimental Autoimmune Uveitis by a Dual-Drug Nanocomposite Formulation with Berberine and Dexamethasone.

PURPOSE: Autoimmune uveitis is a kind of sight-threatening ocular and systemic disorders. Recent treatments on autoimmune uveitis still remain many limitations due to extreme complexity and undetermined pathogenesis. In this study, a novel dual-drug nanocomposite formulation is developed to treat experimental autoimmune uveitis by a combined and sustained therapy method. METHODS: The dual-drug nanocomposite formulation is constructed by integrating berberine (BBR)-loaded mesoporous silica nanoparticles (MSNs) into dexamethasone (DEX)-loaded thermogel (BBR@MSN-DEX@Gel). The BBR@MSN-DEX@Gel is

The Development of the Combination Drug Leukovir® Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review.

The review is devoted to the development and study of the drug Leukovir® (cladribine+ ribavirin) and its use in the treatment of relapsing-remitting and secondary progressive forms of multiple sclerosis, a chronic neurodegenerative disease aiming the risk reduction of relapse and progression of a disability. In clinical trials Leukovir® has proved to be efficient by up to 56 weeks for the treatment of relapsing-remitting and secondary progressive forms of multiple sclerosis. The drug is registered in the Republic of Belarus. The efficacy, safety and tolerability profile of the drug Leukovir® s

Effects of combined test dose and therapeutic drug monitoring strategy in exposure-directed busulfan.

Although exposure-directed busulfan (BU) dosing can improve allogeneic hematopoietic stem cell transplantation outcomes, there is still large variability in BU exposure with test dose alone due to changes in BU clearance caused by drug interactions. We conducted a single-arm phase II trial using the combined test dose and therapeutic drug monitoring strategy (PK-guided group) and compared the outcomes with an external historical cohort receiving a fixed-dose (fixed-dose group). The first eight and second eight doses were adjusted based on the area under the blood concentration-time curve (AUC)

Construction of Stomach Cancer Lesion Detection Combined with Drug Therapy Based on Artificial Intelligence.

The number of stomach cancer (SC) patients is increasing sharply every year, and gastroscope is a common method to check stomach-related diseases. A bulging lesion in the stomach is encountered during a gastroscopy. Due to the change in eating habits, the enhancement of health awareness, and the wide application of gastroscopy, the detection rate and cure rate of tumors have been significantly improved. This has certain clinical value for the early diagnosis and treatment of early SC. In this paper, based on the background of artificial intelligence, image segmentation technology is used to an

Coptis, Pinellia, and Scutellaria as a promising new drug combination for treatment of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (H. pylori) is the most important infectious agent and plays an important role in the progression of chronic … .referencecitationanalysis.com). Next, we used TCM Inheritance Support System V2.5 to identify core drug combinations in the TCM prescriptions. Then, an H. pylori-associated chronic mouse model of gastritis was established. The antibacterial properties and anti-inflammatory potential of the core drug combination were evaluated by the rapid urease test, modified War …

Synergistic Combinations of FDA-Approved Drugs with Ceftobiprole against Methicillin-Resistant Staphylococcus aureus.

New strategies are urgently needed to address the public health threat of antimicrobial resistance. Synergistic agent combinations provide one possible pathway toward addressing this need and are also of fundamental mechanistic interest. Effective methods for comprehensively identifying synergistic agent combinations are required for such efforts. In this study, an FDA-approved drug library was screened against methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300) in the absence and presence of sub-MIC levels of ceftobiprole, a PBP2a-targeted anti-MRSA β-lactam. This screening identi

Coumarin-based combined computational study to design novel drugs against Candida albicans.

Candida species cause the most prevalent fungal illness, candidiasis. Candida albicans is known to cause bloodstream infections. This species is a commensal bacterium, but it can cause hospital-acquired diseases, particularly in COVID-19 patients with impaired immune systems. Candida infections have increased in patients with acute respiratory distress syndrome. Coumarins are both naturally occurring and synthetically produced. In this study, the biological activity of 40 coumarin derivatives was used to create a three-dimensional quantitative structure activity relationship (3D-QSAR) model. T

Integrated Network Pharmacology Approach for Drug Combination Discovery: A Multi-Cancer Case Study.

Despite remarkable efforts of computational and predictive pharmacology to improve therapeutic strategies for complex diseases, only in a few cases have the predictions been eventually employed in the clinics. One of the reasons behind this drawback is that current predictive approaches are based only on the integration of molecular perturbation of a certain disease with drug sensitivity signatures, neglecting intrinsic properties of the drugs. Here we integrate mechanistic and chemocentric approaches to drug repositioning by developing an innovative network pharmacology strategy. We developed

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… Final Drug Prioritization We defined a candidate drug combination as a subset x ⊂ Σ where Σ is the collection of all drugs considered in each experiment. We also evaluated the criteria for each drug combination as follows: (1). … Although our study does not add information for this particular type of drug combination, our in silico drug repurposing approach reveals new drug combinations with high impact on the tumor transcriptional networks. …