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Endometrial receptivity is essential for successful embryo implantation and pregnancy initiation and is regulated via various signaling pathways. Adiponectin, an important adipokine, may be a potential regulator of reproductive system functions. The aim of the present study was to elucidate the regulatory role of adiponectin receptor 1 (ADIPOR1) in endometrial receptivity. The endometrial receptivity between RL95-2 and AN3CA cell lines was confirmed using an in vitro JAr spheroid attachment model. 293T cells were transfected with control or short hairpin (sh)ADIPOR1 vectors and RL95-2 cells were transduced with lentiviral particles targeting ADIPOR1. Reverse transcription-quantitative PCR and immunoblot assays were also performed. ADIPOR1 was consistently upregulated in the endometrium during the mid-secretory phase compared with that in the proliferative phase and in receptive RL95-2 cells compared with that in non-receptive AN3CA cells. Stable cell lines with diminished ADIPOR1 expression caused by shRNA showed reduced E-cadherin expression and attenuated in vitro endometrial receptivity. ADIPOR1 regulated AMP-activated protein kinase (AMPK) activity in endometrial epithelial cells. Regulation of AMPK activity via dorsomorphin and 5-aminoimidazole-4-carboxamide ribonucleotide affected E-cadherin expression and in vitro endometrial receptivity. The ADIPOR1/AMPK/E-cadherin axis is vital to endometrial receptivity. These findings can help improve fertility treatments and outcomes. [ABSTRACT FROM AUTHOR]

Problem: Intravenous immunoglobulin G (IVIG) is an emerging regimen for women with reproductive failures (RF) during‐ or pre‐pregnancy who have aberrant cellular immune reactions. Studies investigating teratogenicity of IVIG have been limited. Herein, we evaluated the fetal teratogenicity of IVIG and IVIG‐related obstetric complications. Method of study: Women who used IVIG during pregnancy due to RF with cellular immune aberrances were enrolled from four medical centers in Korea. The pregnancy outcomes were collected. Results: A total of 370 RF women who used IVIG during their pregnancy were enrolled. Most of the patients started the IVIG therapy before 12 weeks of gestation and 229 women continued IVIG treatment beyond 12 weeks of gestation. The mean age of the subjects was 34.8 years and the mean total dosage of IVIG was 125.3 g. A total of 307 women had livebirths and six of them were twins. Of 301 singleton livebirths, obstetric complications were developed as follows: preterm births (12.0%), gestational diabetes (7.0%), preeclampsia (4.0%), placental abruption (1.3%), placenta previa (4.3%), and placenta accrete (1.7%). Total six cases (1.99%) had major fetal anomalies in livebirths. The incidence of birth defects is similar to those of the general population in Korea and the previous report in infertile women. No IVIG ‐related viral contamination was noted. Conclusion: IVIG use during pregnancy did not increase obstetric complications and fetal teratogenicity. This study can be an evidence of maternal and fetal safety of IVIG administration during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Certain cancers present challenges for treatment because they are resistant to immune checkpoint blockade (ICB), attributed to low tumor mutational burden and the absence of T cell-inflamed features. Among these, glioblastoma (GBM) is notoriously resistant to ICB. To overcome this resistance, the identification of T cells with heightened stemness marked by T-cell factor 1 (TCF1) expression has gained attention. Several studies have explored ways to preserve stem-like T cells and prevent terminal exhaustion. In this study, we investigate a target that triggers stem-like properties in CD8 T cells to enhance the response to ICB in a murine GBM model., Methods: Using Fcgr2b -/- mice and a murine GL261 GBM model, we confirmed the efficacy of anti-programmed cell death protein-1 (PD-1) immunotherapy, observing improved survival. Analysis of immune cells using fluorescence-activated cell sorting and single-cell RNA sequencing delineated distinct subsets of tumor-infiltrating CD8 T cells in Fcgr2b -/- mice. The crucial role of the stem-like feature in the response to anti-PD-1 treatment for reinvigorating CD8 T cells was analyzed. Adoptive transfer of OT-I cells into OVA-expressing GL261 models and CD8 T cell depletion in Fcgr2b -/- mice confirmed the significance of Fcgr2b -/- CD8 T cells in enhancing the antitumor response. Last, S1P 1 inhibitor treatment confirmed that the main source of tumor antigen-specific Fcgr2b -/- CD8 T cells is the tumor-draining lymph nodes (TdLNs)., Results: In a murine GBM model, anti-PD-1 monotherapy and single-Fc fragment of IgG receptor IIb (FcγRIIB) deletion exhibit limited efficacy. However, their combination substantially improves survival by enhancing cytotoxicity and proliferative capacity in tumor-infiltrating Fcgr2b -/- CD8 T cells. The improved response to anti-PD-1 treatment is associated with the tumor-specific memory T cells (Ttsms) exhibiting high stemness characteristics within the tumor microenvironment (TME). Ttsms in the TdLN thrives in a protective environment, maintaining stem-like characteristics and serving as a secure source for tumor infiltration. This underscores the significance of FcγRIIB ablation in triggering Ttsms and enhancing ICB therapy against GBM., Conclusions: Deletion of FcγRIIB on CD8 T cells leads to the generation of a Ttsms, which is localized in TdLN and protected from the immunosuppressive TME. Incorporating these highly stemness-equipped Ttsms enhances the response to anti-PD-1 therapy in immune-suppressed brain tumors., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although the incidence of Mycobacterium abscessus infection has recently increased significantly, treatment is difficult because this bacterium is resistant to most anti-tuberculosis drugs. In particular, M. abscessus is often resistant to available macrolide antibiotics, so therapeutic options are extremely limited. Hence, there is a pressing demand to create effective drugs or therapeutic regimens for M. abscessus infections. The aim of the investigation was to assess the capability of isoegomaketone (iEMK) as a therapeutic option for treating M. abscessus infections. We determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of iEMK for both reference and clinically isolated M. abscessus strains. In addition to time-kill and biofilm formation assays, we evaluated iEMK's capability to inhibit M. abscessus growth in macrophages using an intracellular colony counting assay. iEMK inhibited the growth of reference and clinically isolated M. abscessus strains in macrophages and demonstrated effectiveness at lower concentrations against macrophage-infected M. abscessus than when used to treat the bacteria directly. Importantly, iEMK also exhibited anti-biofilm properties and the potential to mitigate macrolide-inducible resistance, underscoring its promise as a standalone or adjunctive therapeutic agent. Overall, our results suggest that further development of iEMK as a clinical drug candidate is promising for inhibiting M. abscessus growth, especially considering its dual action against both planktonic bacteria and biofilms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Lee, Yu, Yoon, Kang, Lee, Park, Lee, Whang and Kim.)

This study investigated the possible improvement in the antioxidative status and quality characteristics of ready-to-eat (RTE) Samgyetang after adding various black garlic (BG) extracts. The antioxidant activity, total phenolic content (TPC), total flavonoid content (TFC), meat quality indexes, and lipid oxidation rates were measured after receiving one of five different treatments consisting of conventional Samgyetang broth as a negative control, raw garlic (RG) extract as a positive control, BG, oven-dried BG, and maltodextrin-encapsulated BG extract as treatments. Employing retort cooking, fat trimmed carcasses were added to the initially prepared broth together with a phenolic extract that was set at 5% (w/w). A significant intensification of red and yellow color was observed in breast and thigh meat treated with BG extracts, regardless of pretreatment, compared to the negative control and RG. The moisture percentage was affected by the addition of BG extracts, where the encapsulation group retained the highest water content after retorting. In terms of antioxidative status, maltodextrin-encapsulated BG extract was as effective as an oven-dried extract to scavenge free radicals and showed the highest score among samples (p<0.01). The concentration of TFC was found to be the highest and did not differ between encapsulation and oven-dried groups, followed by BG, RG, and the negative control. However, the addition of encapsulated BG extract was the most effective in delaying the formation of malondialdehyde among the samples. Therefore, pre-treatment of BG extract through encapsulation is recommended to develop a higher antioxidative status and quality characteristics of Samgyetang., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)