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Purpose: Lymphoma, the most predominant neoplastic disorder, is divided into Hodgkin and Non-Hodgkin Lymphoma classifications. Immunotherapeutic modalities have emerged as essential methodologies in combating lymphoid malignancies. Chimeric Antigen Receptor (CAR) T cells exhibit promising responses in chemotherapy-resistant B-cell non-Hodgkin lymphoma cases. Methods: This comprehensive review delineates the advancement of CAR-T cell therapy as an immunotherapeutic instrument, the selection of lymphoma antigens for CAR-T cell targeting, and the conceptualization, synthesis, and deployment of CAR-T cells. Furthermore, it encompasses the advantages and disadvantages of CAR-T cell therapy and the prospective horizons of CAR-T cells from a computational research perspective. In order to improve the design and functionality of artificial CARs, there is a need for TCR recognition investigation, followed by the implementation of a quality surveillance methodology. Results: Various lymphoma antigens are amenable to CAR-T cell targeting, such as CD19, CD20, CD22, CD30, the kappa light chain, and ROR1. A notable merit of CAR-T cell therapy is the augmentation of the immune system's capacity to generate tumoricidal activity in patients exhibiting chemotherapy-resistant lymphoma. Nevertheless, it also introduces manufacturing impediments that are laborious, technologically demanding, and financially burdensome. Physical, physicochemical, and physiological limitations further exacerbate the challenge of treating solid neoplasms with CAR-T cells. Conclusion: While the efficacy and safety of CAR-T cell immunotherapy remain subjects of fervent investigation, the promise of this cutting-edge technology offers valuable insights for the future evolution of lymphoma treatment management approaches. Moreover, CAR-T cell therapies potentially benefit patients, motivating regulatory bodies to foster international collaboration.

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PURPOSE: Breast cancer is a common malignancy in women, and its metastasis is a leading cause of cancer-related deaths. Single-cell RNA sequencing (scRNA-seq) can distinguish the molecular characteristics of metastasis and identify predictor genes for patient prognosis. This article explores gene expression in primary breast cancer tumor tissue against metastatic cells in the lymph node and liver using scRNA-seq. METHODS: Breast cancer scRNA-seq data from the Gene Expression Omnibus were used. The data were processed using R and the Seurat package. The cells were clustered and identified using Metascape. InferCNV is used to analyze the variation in copy number. Differential expression analysis was conducted for the cancer cells using Seurat and was enriched using Metascape. RESULTS: We identified 18 distinct cell clusters, 6 of which were epithelial. CNV analysis identified significant alterations with duplication of chromosomes 1, 8, and 19. Differential gene analysis resulted in 17 upregulated and 171 downregulated genes for the primary tumor in the primary tumor vs. liver metastasis comparison and 43 upregulated and 4 downregulated genes in the primary tumor in the primary tumor vs lymph node metastasis comparison. Several enriched terms include Ribosome biogenesis, NTP synthesis, Epithelial dedifferentiation, Autophagy, and genes associated with epithelial-to-mesenchymal transitions. CONCLUSION: No single gene or pathway can clearly explain the mechanisms behind tumor metastasis. Several mechanisms contribute to lymph node and liver metastasis, such as the loss of differentiation, epithelial-to-mesenchymal transition, and autophagy. These findings necessitate further study of metastatic tissue for effective drug development.

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BACKGROUND: Molecules and cytokines can be targeted in cancer therapy. Transforming growth factor-beta (TGF-ß) is a cytokine that acts on protein kinase receptors in the plasma membrane. The signaling pathway of TGF-ß can trigger the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, a signal transduction pathway important in cancer growth and development. However, this PI3K/AKT cascade can be inhibited by phosphatase and tensin homolog (PTEN) tumor suppressor genes. AIM: To determine the inhibitory effect of Holothuria scabra methanol extract (HSE) on breast cancer growth through the TGF-ß/PI3K pathways and PTEN tumor suppressor gene on a breast cancer (BC) mice model. MATERIALS AND METHODS: Female C57BL6 mice were subcutaneously injected with carcinogen DMBA 1 mg/kg body weight (BW) and fed a high-fat diet (HFD). Mice were randomly divided into five groups (n = 6): negative control (NC) administered with a standard diet, positive control (PC) administered with DMBA and HFD, and three treatment groups (T1, T2, and T3) treated with HSE doses of 0.33, 0.66, and 0.99 g/kg BW for 12 weeks. TGF-ß concentration in the blood serum of mice was assessed by ELISA and the PIK3CA and PTEN gene expression by qRT-PCR. RESULTS: The treatment with HSE resulted in a significant decrease in TGF-ß concentrations in the blood sera of treatment groups T1 (35.31 ± 17.33), T2 (43.31 ± 17.42), and T3 (48.67 ± 20.94) pg/mL compared to the PC group (162.09 ± 11.60) pg/mL (p < 0.001). However, only HSE at a dose of 0.99 g/kg BW decreased the PIK3CA gene expression (p = 0.026), and at a dose of 0.66 g/kg BW increased the PTEN expression up to 4.93-fold. CONCLUSION: HSE is capable of inhibiting the TGF-ß/PIK3CA pathway and increasing the PTEN gene expression.

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Melasma is a persistent condition characterized by excessive melanin production in the skin. The management of melasma necessitates a protracted treatment duration, which is associated with diminished levels of patient satisfaction. One effective strategy for mitigating occurrence of melasma is consumption of nutricosmetics with depigmentation properties. The present review aimed to investigate the potential of red fruit as a depigmentation agent. Carotenoids serve a crucial role in human nutrition as a precursor to vitamin A. Carotenoids serve as scavengers of reactive oxygen species generated by ultraviolet radiation. Carotenoids promote skin health. Red fruit, a fruit originating from Papua (Indonesia) has anti-pigmentation properties associated with its ability to block melanogenesis through various protein pathways such as PKA, ERK, and AKT signaling pathways. The consumption of food rich in carotenoids, such as red fruit, has advantageous properties to reduce hyperpigmentation and skin brightening.

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Oxidative stress and inflammation have a role in the development of various diseases. Oxidative stress and inflammation are associated with many proteins, including Kelch ECH associating protein 1 (KEAP1) and inducible nitric oxide synthase (iNOS) proteins. The active compounds contained in Holothuria scabra have antioxidant and anti-inflammatory properties. This study aimed to evaluate the antioxidant and anti-inflammatory activity of sea cucumber's active compounds by targeting KEAP1 and iNOS proteins. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging activity of H. scabra extract were measured spectrophotometrically. The 3-dimensional (3D) structures of sea cucumber's active compounds and proteins were obtained from the PubChem and Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) databases. Molecular docking was performed using AutoDock Vina software. Molecular dynamics simulations were carried out using Yet Another Scientific Artificial Reality Application (YASARA) software with environmental parameters according to the cell's physiological conditions. The membrane permeability test was performed using the PerMM web server. The methanol extract of H. scabra had a weak antioxidant activity against DPPH and strong activity against NO radical. Scabraside and holothurinoside G had the most negative binding affinity values when interacting with the active site of KEAP1 and iNOS proteins. Molecular dynamics simulations also showed that both compounds were stable when interacting with KEAP1 and iNOS. However, scabraside and holothurinoside G were difficult to penetrate the cell plasma membrane, which is seen from the high energy transfer value in the lipid acyl chain region of phospholipids. Scabraside and holothurinoside G are predicted to act as antioxidants and anti-inflammations, but in their implementation to in vitro and in vivo study, it is necessary to have liposomes or nanoparticles, or other delivery methods to help these 2 compounds enter the cell.

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Cancer is a major health problem worldwide and the leading cause of death in many countries. It remains challenging to find anticancer treatments that work efficiently for varying types of cancer cells. Several studies revealed that nuclear factor kappa B (NF-κB) is a family of dimeric transcription factors that induce tumor promotion, progression, and therapeutic resistance, providing evidence that NF-kB may be a promising target for cancer drugs. Some research has found that sea cucumber biocompounds have anticancer properties, but further research is essential to confirm anticancer targets. This manuscript discusses the mechanisms of anticancer targeting the NF-κB signaling pathway induced by sea cucumber-derived compounds. Additional database analysis showed the protein targeted by the compounds involved in several pathways related to the NF-κB network. Moreover, SwissADME predicted druglikeliness properties of the active compounds of sea cucumber. The discussion is expected to provide new insight into the promising potential of these marine natural products for the treatment of many different types of cancers.

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Breast cancer is the most common type of cancer in women globally. The overexpressed proteins, including EGFR, PI3K, AKT1, and CDK4, have a role in the growth of breast cancer cells. The 3D peptide structure of sea cucumber Cucumaria frondosa was modeled and then docked with EGFR, PI3K, AKT1, and CDK4 proteins using AutoDock Vina software. The docking result, which has the best binding affinity value, is continued with molecular dynamics simulation. The docking results showed that all peptides bind to the active sites of the four proteins. WPPNYQW and YDWRF peptides bind to proteins with lower binding affinity values than positive controls. The four proteins were in a stable state when complexed with the WPPNYQW peptide, which was seen from the RMSD and RMSF value. PI3K-YDWRF and AKT1-YDWRF complexes are stable, characterized by high RMSD values and increased volatility in several amino acids. WPPNYQW peptide has high potential as an antibreast cancer agent because it binds to the active sites of the four proteins with low binding affinity values and stable interactions. Meanwhile, the YDWRF peptide interacts with the four proteins with low binding affinity values, but the interaction is only stable on PI3K and AKT1 proteins.

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Information about the role of moderate acute treadmill training in modulating autophagy and mitochondrial markers that might be correlated with alteration of muscle fibre gene expression in rat cardiac muscles is very limited. In this present study, the researchers divided twenty male Wistar rats into four groups: sedentary control, 3, 6 and 15 days and subjected them to treadmill training with moderate intensity (20 m/min), 30 min each day. RNA was extracted from cardiac muscles and stored in temperature of -80°C. Specific primers were utilized for semi-quantitative PCR. Treadmill training decreased autophagy-related gene expression (LC3, p62) and upper stream signalling of autophagy (PIK3CA, Akt and mTOR) in 3 and 6 d, but stimulated gene expression of mitochondrial markers (PGC1α, Cox1, Cox2 and Cox4) in 15 days. αMHC gene expression increased while ßMHC gene expression decreased in 15 days. In line with this, autophagy-related genes increased in 3 and 6 days and returned to baseline in 15 days. The increment in mitochondrial gene expression might be correlated with shifting gene expression of αMHC and ßMHC in 15 days. Taken together, acute adaptation in cardiac muscles is stimulated by genetic modulation of autophagy, mitochondrial marker and muscle fibre that may explain physiological cardiac adaptation after training. This study can be used as a reference for optimizing performance in period of cardiac muscle adaptation stimulated by treadmill training.

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OBJECTIVES: Many studies have reported that tea consumption decreases cardiovascular risk, but the mechanisms remain unclear. Green tea is known to have potent antioxidant and free radical scavenging activities. This study aimed to investigate whether green tea extract (GTE) can protect endothelial progenitors cells (EPCs) against oxidative stress through antioxidant mechanisms. MATERIALS AND METHODS: Mononuclear cells (MNCs) were isolated from peripheral blood by density gradient centrifugation with Ficoll. The cells were then plated on fibronectin-coated culture dishes. After 7 days of culture, EPCs were characterized as adherent cells double positive for DiI-ac-LDL uptake and lectin binding. EPCs were further identified by assessing the expression of CD34/45, CD133, and KDR. EPCs were then treated with hydrogen peroxide (H2O2) at doses of 50, 100, 200 µM and incubated with or without GTE (25 µg/ml). The intracellular reactive oxygen species (ROS) levels were detected by flow cytometry using a 2',7'-dichlorofluorescein diacetate (DCF-DA) fluorescent probe. RESULTS: GTE ameliorated the cell viability of EPCs induced by H2O2 at doses of 50, 100, 200 µM for about 25.47, 22.52, and 11.96% higher than controls, respectively. GTE also decreased the intracellular ROS levels of EPCs induced by H2O2 at doses of 50, 100, 200 µM for about 84.24, 92.27, and 93.72% compared to controls, respectively. CONCLUSION: GTE improves cell viability by reducing the intracellular ROS accumulation in H2O2-induced EPCs.

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OBJECTIVE: Patients with ankylosing spondylitis (AS) can suffer concurrently from inflammatory bowel disease (IBD), as ulcerative colitis (UC) or Crohn's disease (CD). Serological markers have been described to diagnose IBD. We investigated IBD serological markers in AS patients without IBD and whether these antibodies enable differentiating patients with AS and IBD from those without IBD. METHODS: Frequencies of perinuclear antineutrophil cytoplasmic antibodies (pANCA), antibodies to the cell-wall mannan of Saccharomyces cerevisiae (ASCA), and antibodies to porin protein C of Escherichia coli (OmpC) were evaluated in 179 patients: 52 with AS, 50 with UC, 51 with CD, and 26 with IBD and AS. Patient groups were matched for age and sex. All AS patients fulfilled the 1984 modified New York criteria. IBD was ascertained by clinical, endoscopic, and microscopic findings. RESULTS: In 55% of the AS patients without manifest IBD at least one antibody associated with IBD was observed. pANCA, ASCA (IgA and/or IgG), and OmpC antibodies were found in 21%, 30%, and 19% of the AS patients, respectively. pANCA was more frequently present in AS with concurrent UC than in AS alone (OR 8.2, 95% CI 1.2-55.6), thus being an indicator for UC in AS patients. CONCLUSION: Antibodies associated with IBD are detectable in more than half of AS patients without symptoms or signs of IBD. A relatively recent marker in this setting, OmpC antibodies, does not contribute to the differentiation between AS and type of IBD. Presence of pANCA, however, is significantly increased in AS patients who also have UC, and is an indicator to perform endoscopy. These results corroborate a pathophysiological link between AS and IBD.

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