Agung Putra

High-grade serous ovarian carcinoma (HGSC) demonstrates poor prognosis with approximately 80% recurrence rates and significant chemotherapy resistance. Conventional checkpoint inhibitors show limited efficacy (10–15%), necessitating alternative immunotherapeutic approaches. Engineered T lymphocytes, particularly CAR-T and TCR-T cells, have emerged as promising strategies for HGSC. This literature review examines the promising role of engineered T lymphocytes in immunotherapy for HGSC. A comprehensive literature search was conducted across PubMed, Scopus, and Cochrane Library databases for peer-reviewed studies published between 2015 and 2025. Search terms included “engineered T lymphocytes,” “CAR-T cells,” “TCR-T cells,” “ovarian cancer immunotherapy”. CAR-T cells demonstrate promising preclinical antitumor activity in HGSC, with high-avidity T-cell clones showing robust efficacy. Engineered T lymphocytes demonstrate promising approaches across disease contexts. In high-grade serous ovarian carcinoma, Engineered T lymphocytes orchestrate tumor cell apoptosis through coordinated granzyme/perforin and Fas/FasL signaling, enabling rapid cytotoxic elimination of multiple tumor targets.

Breast cancer stem cells (bCSCs) exhibit high plasticity, therapeutic resistance and immune evasion, making them critical targets for effective cancer immunotherapy. Pentagamavunone-1 (PGV-1), a curcumin analog, and its derivative, Chemoprevention Curcumin Analog-1.1 (CCA-1.1), possess cytotoxic and reactive oxygen species (ROS)-modulating properties. However, their potential role in modulating immune-related phenotypes in bCSCs remains unclear. In the study, bCSCs derived from the MDA-MB-231 cell line were treated with PGV-1 or CCA-1.1 to evaluate cytotoxicity, apoptosis, cell cycle distribution, stemness-associated markers and immune checkpoint expression. Cell viability was assessed using the CCK-8 assay. Apoptotic, stemness and immune-checkpoint profiles were analyzed using flow cytometry. PGV-1 exhibited stronger cytotoxicity against bCSCs than CCA-1.1, characterized by lower IC50 values (10.70 and 28.78 µM for PGV-1 and CCA-1.1 respectively at 24 h) and greater induction of apoptosis in a dose-dependent manner. Both compounds at concentrations of 2.67 and 7.19 µM significantly (p < 0.001) induced G2/M cell cycle arrest and reduced the CD44+CD24– stem-like population, indicating loss of stemness and enhanced differentiation. Importantly, PGV-1 significantly downregulated PD-L1 while upregulating CD80, suggesting a shift toward immunophenotypic alterations associated with a potentially more immunogenic profile. These dual effects of cytotoxic and preliminary immunophenotypic modulation highlight the ability of PGV-1 to overcome immune resistance in bCSCs. Further investigation using immune cell–based functional assays or in vivo models is required to validate whether the observed immunophenotypic modulation translates into functional immune activation and to assess the potential of PGV-1 in a co-immunotherapy setting.

Incomplete bacterial eradication despite appropriate antimicrobial therapy contributes to the progression of some bacterial infections toward chronic or recurrent disease. Beyond genetically encoded antimicrobial resistance, bacterial persistence may be sustained by phenotypically tolerant subpopulations, including persister cells, together with biofilm‐associated growth. These states arise within heterogeneous microenvironments shaped by antimicrobial exposure, immune pressure, nutrient and oxygen limitation, and tissue injury. Failure of inflammation to resolve effectively may further promote persistent inflammatory signaling, impaired phagocytic function, localized hypoxia, and extracellular matrix disruption, thereby creating conditions that favor bacterial survival and biofilm stability. This review critically examines the mesenchymal stem cell–derived secretome as a potential host‐directed adjunct for persistent and biofilm‐associated bacterial infections. Rather than reiterating its antimicrobial, immunomodulatory, and regenerative properties, we integrate direct antibiofilm and antimicrobial evidence with indirect host‐mediated mechanisms involving NF‐ κ B modulation, proresolving macrophage responses, efferocytosis, and tissue repair. These actions may converge on host–pathogen niches that sustain bacterial persistence. However, direct evidence that MSC‐secretome reduces persister frequency, reverses bacterial dormancy, or eliminates persister populations remains limited. By distinguishing experimentally demonstrated effects from mechanistically inferred actions, this review proposes a host–pathogen ecological framework for evaluating MSC‐secretome in bacterial persistence. Current evidence remains predominantly preclinical. Key priorities include improved product standardization and potency assessment, validation in physiologically relevant chronic infection models, and clearer definition of dosing, delivery, and combination strategies with conventional antimicrobials.

Ischemic stroke is a major global cause of disability and mortality. Inflammation plays a central role in its pathogenesis, characterized by elevated pro-inflammatory cytokines such as IFN-γ and reduced anti-inflammatory cytokines like IL-10. Mesenchymal stem cells (MSCs), especially those derived from the umbilical cord (UC-MSCs), exhibit enhanced immunomodulatory potential when preconditioned under hypoxia. This study aims to evaluate the effect of hypoxic-preconditioned UC-MSCs administration on IFN-γ and IL-10 levels in an ischemic stroke rat model. This in vivo experimental study employed a randomized posttest-only control group design with four groups of male Wistar rats (n=6 each), ranging from healthy controls, untreated group to stroke-induced groups treated with hypoxic UC-MSCs at different doses (1.5x106 and 3x106). IFN-γ and IL-10 levels in brain tissue of each group were measured via ELISA. Significant reduction in IFN-γ and elevation in IL-10 were observed in UC-MSC-treated groups, particularly at the 3×10⁶ cell dose compared to the untreated ischemic group (p<0.05). Hypoxic UC-MSCs reduce post-stroke inflammation by lowering IFN-γ and enhancing IL-10, indicating a promising immunomodulatory potential.

BACKGROUNDType 2 Diabetes Mellitus (T2DM) is characterized by chronic inflammation and insulin resistance. These factors contribute to pancreatic β-cell apoptosis, reducing insulin production and impairing glucose homeostasis. This study aims to evaluate the protective effects of hypoxic mesenchymal stem cell-derived secretome (HMSCS) and alkaline water on inflammation, apoptosis, and insulin resistance in a T2DM rat model. METHODSAn experimental study was conducted involving 24 male Wistar T2DM model rats (aged 6-8 weeks, 200-250g). They were randomized into four groups: T2DM rats only as negative control (K-), T2DM rats with metformin as positive control (K+), HMSCS treatment (P1), and HMSCS plus alkaline water group (P2). Caspase-3 expression was measured to assess apoptosis levels using RT-PCR, while homeostatic model assessment for insulin resistance (HOMA-IR) was measured using ELISA. One way ANOVA followed by a post hoc LSD test were used to analyse the data. RESULTSThe P1 group (3.03 ± 1.26 a.u) and P2 group (2.93 ± 0.52 a.u.) had significantly lower caspase-3 expression compared to K- group (6.66 ± 2.76 a.u.) (p0.05). Additionally, P2 group (6.76 ± 0.96) had a significantly lower HOMA-IR than K- group (18.92 ± 2.63) and K+ group (10.85 ± 1.39) (p<0.05), and similarly the P1 (7.71 ± 0.53) group also showed significant difference from K- and K+ groups (p<0.05). CONCLUSIONHigher doses of HMSCS and alkaline water are associated with reduced pancreatic β-cell apoptosis and improved insulin sensitivity, highlighting its potential as a novel therapeutic approach for T2DM.

Aim to investigate the potential of SG followed by injection of MSCs in type 2 diabetic rats with obesity in improving IR. Methods This study used a pre and post-control group design with 24 rats divided into three groups: Control (C), SG, and SG + MSCs (SG+M). On day 10, the level of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), triglyceride (TG), pancreatic beta cells, and homeostasis model assessment of IR (HOMA-IR) was evaluated using qRT-PCR, ELISA, and immunohistochemistry. Results A significant decrease of TNF-α (1.179 pg/mL), CRP(209 pg/mL), and TG levels (82,83  15,02pg/mL) in all treatment groups on day 10, in which SG + M group showed optimum inhibition was found (p < 0.05). This result was in line with the optimum increase of VEGF (8,1500 ± 2,47397) and pancreatic beta cell(10,1783±0,47) in SG + M group (p < 0.05). Moreover, our study also revealed the optimum decrease of HOMA-IR in SG+M group on day 10 (49,8233 ± 1,07303). Conclusion A combination of SG and MSCs can optimally improve insulin resistance by inhibiting TNF-α, CRP, and TG level and upregulating VEGF and pancreatic beta cell in an obese T2DM rat model

Background Repeated ultraviolet-B (UVB) exposure induces significant collagen degradation, primarily through overproduction of reactive oxygen species, which subsequently drives an inflammatory cascade. Hypoxia-preconditioned mesenchymal stem cells (H-MSCs) constitute a promising therapeutic approach to counteract collagen loss by modulating inflammatory pathways. This study aimed to evaluate the potential of H-MSCs in regulating NF-κB p65 and IL-1β expression in a collagen loss rat model, highlighting their therapeutic efficacy. Methods Twenty-five healthy male Wistar rats were randomly assigned to five groups: K1 (healthy controls), K2 (collagen loss), K3 (collagen loss + hyaluronic acid), K4 (collagen loss + 2.5 × 10⁵ H-MSCs), and K5 (collagen loss + 5 × 10⁵ H-MSCs). Collagen loss was induced by UVB radiation (peak wavelength: 302 nm) for 2 weeks. mRNA expression of NF-κB p65 was quantified by qRT-PCR, while IL-1β levels were assessed using ELISA. The rats were maintained for 14 days before being sacrificed, to allow the H-MSCs to exert their therapeutic effects. Data analysis was by One-way ANOVA with Tukey’s post-hoc test. Results The administration of H-MSCs significantly reduced IL-1β levels in groups K4 (633.14±63.76 pg/mL) and K5 (520.80±123.82 pg/mL) compared to group K2 (931.93±205.80 pg/mL) (p<0.05), with group K5 showing the most substantial reduction. Moreover, H-MSC injection in groups K4 and K5 effectively reduced NF-κB p65 expression levels (1.13±0.50 a.u. and 0.72±0.22 a.u., respectively), compared to group K2 (2.47±0.50 a.u.) (p<0.05), with group K5 providing optimum inhibition. Conclusion This study demonstrated that H-MSCs effectively attenuate UVB-induced inflammation and modulate key inflammatory pathways.

Diabetic foot ulcer (DFU) is a prevalent and severe complication of diabetes mellitus (DM), posing significant economic and psychological challenges for patients. This study aimed to evaluate the therapeutic efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for DFU by conducting a systematic review and meta-analysis of clinical outcomes, including ulcer healing, ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO₂), and Hemoglobin A1c (HbA1c) levels. A comprehensive systematic search was performed across the Cochrane, PubMed, and Scopus databases to identify relevant studies suitable for meta-analysis. Key outcomes assessed included ABI, ulcer healing, TcPO₂, and HbA1c. Dichotomous data were reported as odds ratios (OR) with corresponding 95% confidence intervals (CIs), whereas continuous outcomes were evaluated as standard mean difference (SMD) with 95% CIs. Statistical analyses were conducted using R (version 4.3.2).The meta-analysis included four studies comprising 115 participants (59 cases and 56 controls). UC-MSC therapy demonstrated superior efficacy compared to controls, with significant improvements in complete ulcer closure rates [OR = 48.97 (1.38, 1736.47)], ABI [SMD = 1.34 (0.78, 1.90)], and TcPO₂ [SMD = 1.90 (-0.38, 4.18)], along with a marked reduction in HbA1c levels [SMD = -2.63 (-4.80, -0.45)]. However, the wide confidence intervals for some outcomes (e.g., OR = 48.97 [1.38, 1736.47]) suggest uncertainty and highlight the need for cautious interpretation of these findings. UC-MSC therapy shows promise as a treatment for DFU, with potential benefits in ulcer healing, ABI, TcPO₂, and HbA1c reduction. However, the small number of studies and wide confidence intervals underscore the need for larger, more robust, multi-center, randomized, double-blind, placebo-controlled trials with extended follow-up periods to confirm these findings and optimize UC-MSC therapeutic strategies for DFU.

Prolonged exposure to high-intensity UVB radiation can induce the formation of Reactive Oxygen Species (ROS), inhibit alpha-smooth muscle actin (α-SMA), and collagen type 1 expression, leading to skin hyperpigmentation. This study aimed to investigate the effect of topical application of stink bean peel extract gel on the expression of α-SMA and collagen type 1 genes in the skin tissue of hyperpigmentation rats. Stink bean peel extract gel was prepared by mixing ethanol extract of stink bean peel with a gel base (Catechu) to make 10% and 20% formulations. Hyperpigmentation was induced in rats by exposure to UVB radiation (λ302 nm, 390 mj/cm2/day) three times a week for two weeks. The animals were divided into four groups: K1 (healthy rats), K2 (negative control), K3 (10% extract gel, and K4 (20% extract gel). The effect of stink bean peel extract gel treatment on the expression of α-SMA and collagen type 1 genes was analyzed using Real-Time Quantitative Reverse Transcription polymerase chain reaction (qRT-PCR). qRT-PCR analysis indicated a significant (p < 0.05) increase in the expression of α-SMA gene in group K4 with a mean expression ratio of 3.11±1.08 compared to the negative control (0.67±0.17). Collagen type 1 gene expression also increased significantly in K3 and K4 groups with expression ratios of 2.21±0.68, and 2.12±0.73, respectively compared to the negative control (0.51±0.14). Findings from this study has shown that stink bean peel extract has the potential to be used as a protective and therapeutic agent against UVB-induced skin damage.

Skin aging is marked by decreased elasticity and increased wrinkle formation, often associated with altered expression of key genes such as APAF-1 and Survivin. Exposure to UVB radiation, particularly in tropical regions, accelerates collagen degradation, thereby heightening the risk of premature aging. Mesenchymal stem cell-derived hypoxic exosomes (MSCs-Exosome Hipoksia) have shown potential in suppressing APAF-1 expression and enhancing Survivin levels, although their effects on UVB-induced skin damage have not been fully explored. This study investigated the impact of MSCs-Exosome Hipoksia on APAF-1 and Survivin gene expression in UVB-exposed rat skin. Rats with reduced collagen levels due to UVB exposure were randomly assigned into four groups: normal control (KN; UVB + 0.9% sodium chloride 300 µL), positive control (KP; UVB + hyaluronic acid 200 µL), treatment group 1 (T1; UVB + MSCs-Exosome Hipoksia 200 µL), and treatment group 2 (T2; UVB + MSCs-Exosome Hipoksia 300 µL). The T2 group demonstrated the lowest APAF-1 expression (1.03 ± 0.33 pg/mL) and the highest Survivin expression (4.35 ± 0.73 pg/mL). Both treatment groups (T1 and T2) showed statistically significant reductions in APAF-1 and increases in Survivin expression compared to control groups (p < 0.05). These findings indicate that MSCs-Exosome Hipoksia, particularly at a dose of 300 µL, may effectively modulate molecular markers associated with skin aging and hold therapeutic potential in mitigating UVB-induced dermal damage.