A novel strategy of co-expressing CXCR5 and IL-7 enhances CAR-T cell effectiveness in osteosarcoma.

Background: Solid tumors are characterized by a low blood supply, complex stromal architecture, and immunosuppressive milieu, which inhibit CAR-T cell entry and survival. CXCR5 has previously been employed to increase CAR-T cell infiltration into CXCL13+ cancers. On the other hand, IL-7 improves the survival and persistence of T cells inside a solid tumor milieu.

GPR97 depletion aggravates imiquimod-induced psoriasis pathogenesis via amplifying IL-23/IL-17 axis signal pathway.

Skin psoriasis is defined as receiving external stimulation to activate skin dendritic cells (DCs) which can release interleukin 23 (IL-23) to interlink the innate and adaptive immunity as well as induce T helper 17 (Th17) cell differentiation leading to elevated production of interleukin 17 (IL-17) for keratinocytes over production. This autoimmune loop in psoriasis pathogenesis is influenced by G protein-coupled receptor (GPCR) signalling transduction, and in particular, function of adhesion molecule GPR97 in psoriasis endures to be utterly addressed. In this research, our team allocated GPR97 depletion (GPR97), GPR97 conditional depletion on dendritic cell (DC-cKO), and keratin 14-conditional knockout (K14-cKO) mice models to explore the function of GPR97 which influences keratinocytes and skin immunity.

Intrinsic ADRB2 inhibition improves CAR-T cell therapy efficacy against prostate cancer.

Chimeric antigen receptor (CAR)-T cell therapy has shown limited success in patients with solid tumors. Recent in vitro and in vivo data have shown that adrenoceptor beta-2 (ADRB2) is a novel checkpoint receptor that inhibits T cell-mediated anti-tumor responses. To inhibit ADRB2-mediated inhibitory signaling, we downregulated ADRB2 in CAR-T (shβ-CAR-T) cells via RNA interference, assessed different parameters, and compared them with conventional second-generation CAR-T cells.

shRNA-mediated gene silencing of HDAC11 empowers CAR-T cells against prostate cancer.

Epigenetic mechanisms are involved in several cellular functions, and their role in the immune system is of prime importance. Histone deacetylases (HDACs) are an important set of enzymes that regulate and catalyze the deacetylation process. HDACs have been proven beneficial targets for improving the efficacy of immunotherapies.

Modulating Cholesterol Metabolism via ACAT1 Knockdown Enhances Anti-B-Cell Lymphoma Activities of CD19-Specific Chimeric Antigen Receptor T Cells by Improving the Cell Activation and Proliferation.

CD19-specific CAR-T immunotherapy has been extensively studied for the treatment of B-cell lymphoma. Recently, cholesterol metabolism has emerged as a modulator of T lymphocyte function and can be exploited in immunotherapy to increase the efficacy of CAR-based systems. Acetyl-CoA acetyltransferase 1 (ACAT1) is the major cholesterol esterification enzyme.

Co-expression of IL-4/IL-15-based inverted cytokine receptor in CAR-T cells overcomes IL-4 signaling in immunosuppressive pancreatic tumor microenvironment.

The efficacy of CAR-T cell therapy has been hindered by several factors that are intrinsic to the tumor microenvironment. Many strategies are being employed to overcome these barriers and improve immunotherapies efficacy. Interleukin (IL)- 4 is a cytokine released by tumor cells inside the tumor microenvironment and it can oppose T cell effector functions via engagement with the IL-4 receptor on the surface of T cells.

β2-Adrenergic Receptor Mediated Inhibition of T Cell Function and Its Implications for CAR-T Cell Therapy.

The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of the tumor microenvironment, nor-adrenaline (NA) is poured in by innervating nerves and tumor tissues itself.

Collaterally Sensitive β-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant (MRSA) Biofilms.

Methicillin-resistant (MRSA) is among the leading causes of nosocomial infections and forms biofilms, which are difficult to eradicate because of their increasing resistance to antimicrobial agents. This is especially true for pre-existing biofilms. The current study focused on evaluating the efficacy of three β-lactam drugs, meropenem, piperacillin, and tazobactam, alone and in combination against the MRSA biofilms.

Hyperglycemia-associated Alzheimer's-like symptoms and other behavioral effects attenuated by L. Extract in alloxan-induced diabetic rats.

Diabetes mellitus is a chronic metabolic complaint with numerous short- and long-term complications that harm a person's physical and psychological health. L. is a traditional medicine used in the treatment of diabetes to reduce complications related to behavior.

An overview of viral mutagenesis and the impact on pathogenesis of SARS-CoV-2 variants.

Viruses are submicroscopic, obligate intracellular parasites that carry either DNA or RNA as their genome, protected by a capsid. Viruses are genetic entities that propagate by using the metabolic and biosynthetic machinery of their hosts and many of them cause sickness in the host. The ability of viruses to adapt to different hosts and settings mainly relies on their ability to create variety in a short interval of time.

Quantification of rosmarinic acid from different plant species of lower Himalayan region and expression analysis of underlying L-Phenylalanine pathway.

This study adopts a very effective high-performance liquid chromatography (HPLC) technique for the quantitative determination of rosmarinic acid (RA) and PCR-based amplification of biosynthetic key regulators in Isodon rugosus, Daphne mucronata, and Viburnum grandiflorum from the lower Himalayan regions. Rosmarinic acid is engaged in a variety of biological processes and has significant industrial significance. In this study, it was identified from crude methanolic extract using thin-layer chromatography with a standard, and its content was quantified using HPLC without interrupting spikes using a mixture of methanol and deionized water containing acetonitrile (70:30 v/v) and acetic acid (0.

Isoprenaline and salbutamol inhibit pyroptosis and promote mitochondrial biogenesis in arthritic chondrocytes by downregulating β-arrestin and GRK2.

Rheumatoid arthritis and osteoarthritis overlap many molecular mechanisms of cartilage destruction. Wear and tear in cartilage is chondrocyte-mediated, where chondrocytes act both as effector and target cells. In current study, role of β2-AR was studied in chondrocytes both and .

Suppression of 4.1R enhances the potency of NKG2D-CAR T cells against pancreatic carcinoma via activating ERK signaling pathway.

Pancreatic carcinoma (PC) is one of the most common malignancies. Chimeric antigen receptor (CAR)-modified T cells has achieved remarkable efficacy in the treatment of hematological malignancies. However, lack of tumor-specific targets and the existence of inhibitory factors limit the function of CAR T cells when treating solid tumors.

Characterization of bio-fabricated silver nanoparticles for distinct anti-fungal activity against sugarcane phytopathogens.

Advanced research, development, and application of silver nanoparticles is proceeding in recent times due to their incredible utilization in various fields. Present study was focused on the production, characterization, and antifungal activities of silver nanoparticles (AgNPs). An environment friendly extracellular biosynthetic approach was adopted to produce the AgNPs by using bacteria, fungi, and sugarcane husk.

CD19-CAR-T Cells Bearing a KIR/PD-1-Based Inhibitory CAR Eradicate CD19HLA-C1 Malignant B Cells While Sparing CD19HLA-C1 Healthy B Cells.

B cell aplasia caused by "on-target off-tumor" toxicity is one of the clinical side effects during CD19-targeted chimeric antigen receptor (CAR) T (CD19-CAR-T) cells treatment for B cell malignancies. Persistent B cell aplasia was observed in all patients with sustained remission, which increased the patients' risk of infection. Some patients even died due to infection.

Co-Expression of IL-7 Improves NKG2D-Based CAR T Cell Therapy on Prostate Cancer by Enhancing the Expansion and Inhibiting the Apoptosis and Exhaustion.

Chimeric antigen receptor (CAR) T-cell therapy is a promising approach in treating solid tumors but the therapeutic effect is limited. Prostate cancer is a typical solid malignancy with invasive property and a highly immunosuppressive microenvironment. Ligands for the NKG2D receptor are primarily expressed on many cancer cells, including prostate cancer.

Multi-stress tolerant PGPR Bacillus xiamenensis PM14 activating sugarcane (Saccharum officinarum L.) red rot disease resistance.

Sustainability in crop production has emerged as one of the most important concerns of present era's agricultural systems. Plant growth promoting bacteria (PGPB) has been characterized as a set of microorganisms used for enhancing plant growth and a tool for biological control of phytopathogens. However, the inconsistent performance of these bacteria from laboratory/greenhouse to field level has emerged due to prevailing abiotic stresses in fields.

Full time occlusion VS part time occlusion in treatment of monocular amblyopia.

Objective: To compare improvement in Best Corrected Visual Acuity (BCVA) by Full Time Occlusion (FTO) or Part Time Occlusion (PTO) technique in children with monocular amblyopia.

Methods: This randomized control trial was conducted at Combined Military Hospital, Gujranwala from April 2018 to June 2019. A total of 52 children, diagnosed with non-pathological ametropic amblyopia were randomly divided in two groups.

Factors affecting the visual outcome in acute central serous chorioretinopathy.

Objective: To determine the visual outcome in patients with acute Central serous chorioretinopathy (CSCR) and to analyze the association of clinical, angiographic and tomographic factors with final visual outcome in Pakistani population.

Methods: This study was conducted at AFIO Rawalpindi and PNS Shifa Naval hospital Karachi from November 2011 to August 2016. Fifty five eyes of 53 patients with acute CSCR were included.

Studies on phytochemical, antioxidant, anti-inflammatory and analgesic activities of Euphorbia dracunculoides.

Background: Plants provide an alternative source to manage various human disorders due to diverse metabolites. Euphorbia dracunculoides of family Euphorbiaceae is used by local practitioners in rheumatism, epilepsy, edema, snake bite, warts and also possesses diuretic and purgative effects. The present study evaluated the antioxidant, anti-inflammatory and analgesic activities of various extracts of E.

Ethnomedicinal plant use value in the Lakki Marwat District of Pakistan.

Aim Of The Study: Medicinal plants are regional treasures for the treatment of many ailments. The present research investigated and documented knowledge of indigenous commonly used medicinal plants, including traditional names, preparations and uses, in the Lakki Marwat District of Pakistan. The information gathered was statistically analyzed using the ICF method to establish baseline data for more comprehensive investigations of bioactive compounds of indigenous medicinal plants.