Hyaluronic-Acid-Functionalized Tofacitinib Loaded Transethosomes for Targeted Drug Delivery in Rheumatoid Arthritis.

The Janus kinase inhibitor tofacitinib (TOF) is an FDA-approved drug for rheumatoid arthritis (RA) treatment, but its long-term oral use leads to significant systemic side effects. The present research aimed to conquer these challenges by formulating hyaluronic-acid-coated transethosomes (HA-TOF-TE), a novel system for targeted, topical delivery of TOF to reduce systemic toxicity and improve therapeutic efficacy. Transethosomes were synthesized via the cold sonication technique with HA functionalization enabling CD44 receptor-mediated targeting of inflamed synovial tissue.

Analysis of the ubiquitin-modified proteome identifies novel host factors in Kaposi's sarcoma herpesvirus lytic reactivation.

Unlabelled: Kaposi's sarcoma herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma and is associated with primary effusion lymphoma (PEL), multicentric Castleman's disease, and two inflammatory diseases. KSHV-associated cancers are primarily associated with genes expressed during latency, while other pathologies are associated with lytic gene expression. The major lytic switch of the virus, Replication and Transcription Activator (RTA), interacts with cellular machinery to co-opt the host ubiquitin proteasome system to evade the immune response as well as activate the program of lytic replication.

Green Light Exposure Reduces Primary Hyperalgesia and Proinflammatory Cytokines in a Rodent Model of Knee Osteoarthritis: Shedding Light on Sex Differences.

Knee osteoarthritis (OA) often causes chronic pain that disproportionately affects females. Proinflammatory cytokines TNF-α, IL-1β, and IL-6 are key effectors of OA pathological changes. Green light shows potential as an alternative intervention for various pain conditions.

Co-infection is linked to infection prevalence and intensity in oysters amidst high environmental and spatial variation.

Co-infecting parasites modify infection outcomes in the wild. However, it is unclear how multiple environmental factors influence co-infection. The Chesapeake Bay metapopulation of the eastern oyster, Crassostrea virginica, provides an opportunity to test the importance of co-infection across heterogeneous environments because multiple parasites infect oysters across a broad salinity gradient.

CD27 signaling inhibits tumor growth and metastasis via CD8 + T cell-independent mechanisms in the B16-F10 melanoma model.

CD27 belongs to the tumor necrosis factor receptor superfamily and acts as a co-stimulatory molecule, modulating T and B cell responses. CD27 stimulation enhances T cell survival and effector functions, thus providing opportunities to develop therapeutic strategies. The current study aims to investigate the role of endogenous CD27 signaling in tumor growth and metastasis.

Mesua assamica (King & Prain) kosterm. bark ethanolic extract attenuates rheumatoid arthritis via down-regulating TLR4/NF-κB/COX-2/iNOS and activation of Nrf2/HO-1 pathways: A comprehensive study on in-vitro and in-vivo models.

Ethnopharmacological Relevance: Rheumatoid arthritis (RA) is a multifactorial, polygenic inflammatory disease. Mesua assamica (King & Prain) Kosterm. (MA) is an endangered medicinal plant indigenous to South Asia, primarily to Assam in India.

Quantification of Human Photoreceptor-Retinal Pigment Epithelium Macular Topography with Adaptive Optics-Optical Coherence Tomography.

Photoreceptors (PRs) and retinal pigment epithelial (RPE) cells form a functional unit called the PR-RPE complex. The PR-RPE complex plays a critical role in maintaining retinal homeostasis and function, and the quantification of its structure and topographical arrangement across the macula are important for understanding the etiology, mechanisms, and progression of many retinal diseases. However, the three-dimensional cellular morphology of the PR-RPE complex in living human eyes has not been completely described due to limitations in imaging techniques.

Reassessing granzyme B: unveiling perforin-independent versatility in immune responses and therapeutic potentials.

The pivotal role of Granzyme B (GzmB) in immune responses, initially tied to cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, has extended across diverse cell types and disease models. A number of studies have challenged conventional notions, revealing GzmB activity beyond apoptosis, impacting autoimmune diseases, inflammatory disorders, cancer, and neurotoxicity. Notably, the diverse functions of GzmB unfold through Perforin-dependent and Perforin-independent mechanisms, offering clinical implications and therapeutic insights.

Deep PIM kinase substrate profiling reveals new rational cotherapeutic strategies for acute myeloid leukemia.

Provirus integration site for Moloney murine leukemia virus (PIM) family serine/threonine kinases perform protumorigenic functions in hematologic malignancies and solid tumors by phosphorylating substrates involved in tumor metabolism, cell survival, metastasis, inflammation, and immune cell invasion. However, a comprehensive understanding of PIM kinase functions is currently lacking. Multiple small-molecule PIM kinase inhibitors are currently being evaluated as cotherapeutics in patients with cancer.

Angiolipoma associated with antiretroviral switch therapy: a case report.

Background: Angiolipomas have been well described in patients with HIV exposed to protease inhibitors with possible resolution after switching to non-nucleoside reverse transcriptase inhibitor-based regimens. Resolution of symptoms have occurred with switches to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens; however, little is known regarding the development of angiolipomas when switching from NNRTI- to modern, integrase strand transfer inhibitor-based regimens. We describe a patient who underwent switch therapy from tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/FTC/EFV) to tenofovir alafenamide/FTC/bictegravir (TAF/FTC/BIC) who later developed angiolipomas.

TNIK inhibition sensitizes TNIK-overexpressing lung squamous cell carcinoma to radiotherapy.

Most patients with lung squamous cell carcinoma (LSCC) undergo chemotherapy, radiotherapy, and adjuvant immunotherapy for locally advanced disease. The efficacy of these treatments is still limited due to dose-limiting toxicity or locoregional recurrence. New combination approaches and targets such as actionable oncogenic drivers are needed to advance treatment options for LSCC patients.

Context-Responsive Nanoparticle Derived from Synthetic Zwitterionic Ionizable Phospholipids in Targeted CRISPR/Cas9 Therapy for Basal-like Breast Cancer.

The majority of triple negative breast cancers (TNBCs) are basal-like breast cancers (BLBCs), which tend to be more aggressive, proliferate rapidly, and have poor clinical outcomes. A key prognostic biomarker and regulator of BLBC is the Forkhead box C1 (FOXC1) transcription factor. However, because of its functional placement inside the cell nucleus and its structural similarity with other related proteins, targeting FOXC1 for therapeutic benefit, particularly for BLBC, continues to be difficult.

Repurposing beta-blockers for combinatory cancer treatment: effects on conventional and immune therapies.

Beta-adrenergic receptor signaling regulates cellular processes associated with facilitating tumor cell proliferation and dampening anti-tumor immune response. These cellular processes may lead to compromised tumor control and cancer progression. Based on this ramification, Beta-blockers (BBs) have emerged as a potential treatment by inhibiting beta-adrenergic receptor signaling.

Diagnosis of COVID-19 with simultaneous accurate prediction of cardiac abnormalities from chest computed tomographic images.

COVID-19 has potential consequences on the pulmonary and cardiovascular health of millions of infected people worldwide. Chest computed tomographic (CT) imaging has remained the first line of diagnosis for individuals infected with SARS-CoV-2. However, differentiating COVID-19 from other types of pneumonia and predicting associated cardiovascular complications from the same chest-CT images have remained challenging.

CD45.1/CD45.2 Congenic Markers Induce a Selective Bias for CD8+ T Cells during Adoptive Lymphocyte Reconstitution in Lymphocytopenia Mice.

CD45.1/CD45.2 congenic markers have been used to track hematopoietic lineage differentiation following hematopoietic stem and progenitor cell (HSPC) transplantation.

Highly-Specific Single-Stranded Oligonucleotides and Functional Nanoprobes for Clinical Determination of Chlamydia Trachomatis and Neisseria Gonorrhoeae Infections.

Early detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is the key to controlling the spread of these bacterial infections. An important step in developing biosensors involves identifying reliable sensing probes against specific genetic targets for CT and NG. Here, the authors have designed single-stranded oligonucleotides (ssDNAs) targeting mutually conserved genetic regions of cryptic plasmid and chromosomal DNA of both CT and NG.

Understanding the Immunomodulatory Effects of Bovine Colostrum: Insights into IL-6/IL-10 Axis-Mediated Inflammatory Control.

Bovine colostrum (COL), the first milk secreted by lactating cows postpartum, is a rich source of bioactive compounds that exert a significant role in the survival, growth, and immune development of neonatal calves. This study investigated the immunomodulatory effects of COL on cytokine production in vitro using a Caco-2/THP-1 macrophage co-culture model stimulated with Phorbol 12-myristate 13-acetate (PMA). COL pretreatment significantly reduced IL-6 (241.

Calcium and bicarbonate signaling pathways have pivotal, resonating roles in matching ATP production to demand.

Mitochondrial ATP production in ventricular cardiomyocytes must be continually adjusted to rapidly replenish the ATP consumed by the working heart. Two systems are known to be critical in this regulation: mitochondrial matrix Ca ([Ca]) and blood flow that is tuned by local cardiomyocyte metabolic signaling. However, these two regulatory systems do not fully account for the physiological range of ATP consumption observed.

Synthesis of 1-(2-Hydroxyphenyl)- and (3,5-Dichloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic Acid Derivatives as Promising Scaffolds for the Development of Novel Antimicrobial and Anticancer Agents.

Increasing antimicrobial resistance among Gram-positive pathogens and pathogenic fungi remains one of the major public healthcare threats. Therefore, novel antimicrobial candidates and scaffolds are critically needed to overcome resistance in Gram-positive pathogens and drug-resistant fungal pathogens. In this study, we explored 1-(2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid and its 3,5-dichloro-2-hydroxyphenyl analogue for their in vitro antimicrobial activity against multidrug-resistant pathogens.

The Influence of Feeding with Colostrum and Colostrum Replacer on Major Blood Biomarkers and Growth Performance in Dairy Calves.

Bovine colostrum (BC) is the first milk produced by lactating cows after parturition. BC is rich in various amino acids, proteins, and fats essential for the nutrition of the neonate calves. Despite the evident beneficial effect of BC on calves, the effect of BC on blood biomarkers is poorly understood.

Synthesis and Biological Activity Characterization of Novel 5-Oxopyrrolidine Derivatives with Promising Anticancer and Antimicrobial Activity.

The 1-(4-acetamidophenyl)-5-oxopyrrolidine carboxylic acid was applied for synthesizing derivatives bearing azole, diazole, and hydrazone moieties in the molecule. Modification of an acetamide fragment to the free amino group afforded compounds with two functional groups, which enabled to provide a series of 4-substituted-1-(4-substituted phenyl)pyrrolidine-2-ones. The resulted compounds and - were subjected to the in vitro anticancer and antimicrobial activity determination.

A Machine Learning Framework for Detecting COVID-19 Infection Using Surface-Enhanced Raman Scattering.

In this study, we explored machine learning approaches for predictive diagnosis using surface-enhanced Raman scattering (SERS), applied to the detection of COVID-19 infection in biological samples. To do this, we utilized SERS data collected from 20 patients at the University of Maryland Baltimore School of Medicine. As a preprocessing step, the positive-negative labels are obtained using Polymerase Chain Reaction (PCR) testing.

A narrative review on the role of carbon nanoparticles in oncology.

The lymphatic system is the first site of metastasis for most tumors and is a common reason for the failure of cancer therapy. The lymphatic system's anatomical properties make it difficult to deliver chemotherapy agents at therapeutic concentrations while avoiding systemic toxicity. Carbon nanoparticles offer a promising alternative for identifying and transporting therapeutic molecules.