Single-Center Experience of Parathyroidectomy Using Intraoperative Parathyroid Hormone Monitoring.

Background and Objectives: Hyperparathyroidism (HPT) is a rare endocrine disease associated with the elevated metabolism of calcium, vitamin D, and phosphate by the hyperfunctioning of the parathyroid glands. Here, we report our experience of parathyroidectomy using intraoperative parathyroid hormone (IOPTH) monitoring in a single tertiary hospital. Materials and Methods: From October 2018 to January 2022, a total of 47 patients underwent parathyroidectomy for HPT. We classified the patients into two groups-primary HPT (PHPT, n = 37) and renal HPT (RHPT, n = 10)-and then reviewed the patients' data, including their general characteristics, laboratory results, and perioperative complications. Results: Thirty-five of the thirty-seven patients in the PHPT group underwent focused parathyroidectomy, while all ten patients in the RHPT group underwent subtotal parathyroidectomy. IOPTH monitoring based on the Milan criteria was used in all cases. Preoperative and 2-week, 6-month, and 12-month postoperative parathyroid hormone (PTH) levels were within the normal range in the PHPT group, whereas they were higher than normal in the RHPT group. Transient hypocalcemia occurred only in the RHPT group, with calcium levels returning to normal levels 12 months after surgery. Conclusions: Parathyroidectomy with IOPTH monitoring in our hospital showed favorable clinical outcomes. However, owing to the small number of patients due to the low frequency of parathyroid disease, long-term, prospective studies are needed in the future.

Non-invasive stem cell tracking in hindlimb ischemia animal model using bio-orthogonal copper-free click chemistry.

Labeling of stem cells aims to distinguish transplanted cells from host cells, understand in vivo fate of transplanted cells, particularly important in stem cell therapy. Adipose-derived mesenchymal stem cells (ASCs) are considered as an emerging therapeutic option for tissue regeneration, but much remains to be understood regarding the in vivo evidence. In this study, a simple and efficient cell labeling method for labeling and tracking of stem cells was developed based on bio-orthogonal copper-free click chemistry, and it was applied in a mouse hindlimb ischemia model. The human ASCs were treated with tetra-acetylated N-azidoacetyl-d-mannosamine (Ac4ManNAz) to generate glycoprotein with unnatural azide groups on the cell surface, and the generated azide groups were fluorescently labeled by specific binding of dibenzylcyclooctyne-conjugated Cy5 (DBCO-Cy5). The safe and long-term labeling of the hASCs by this method was first investigated in vitro. Then the DBCO-Cy5-hASCs were transplanted into the hindlimb ischemia mice model, and we could monitor and track in vivo fate of the cells using optical imaging system. We could clearly observe the migration potent of the hASCs toward the ischemic lesion. This approach to design and tailor new method for labeling of stem cells may be useful to provide better understanding on the therapeutic effects of transplanted stem cells into the target diseases.

Testing the Reliability and Validity of the Korean Version of the Pittsburgh Sleep Quality Index Using Fitbit Devices: A Cross-Sectional Analysis.

Background: Sleep disorders and insomnia are prevalent worldwide, with negative health outcomes. The Pittsburgh Sleep Quality Index (PSQI) is a widely used self-report assessment tool for evaluating sleep quality, comprising seven subdomains. The Korean version of the PSQI (PSQI-K) has been tested for reliability and validity in small sample sizes but lacks large-scale validation using objective measures. Methods: This study was conducted with 268 Korean adults attending health check programs. Participants completed the PSQI-K questionnaire and wore Fitbit devices (Fitbit Inc., USA) to ascertain sleep parameters. Reliability was analyzed using the Cronbach's α coefficient, and construct validity was determined through factor analysis. Criteria validity was assessed by correlating their index scores with Fitbit sleep parameters. We identified the optimal cutoff for detecting sleep disorders. Results: The Cronbach's α coefficient was 0.61, indicating adequate internal consistency. Factor analysis revealed three factors, explaining 48.2% of sleep quality variance. The index scores were negatively correlated with Fitbit sleep efficiency, total sleep time, and number of awakenings (P<0.05). The optimal cutoff point for identifying sleep disorder groups was ≥6. Conclusion: The PSQI-K demonstrated good reliability and validity when correlated with Fitbit sleep parameters, offering a practical screening tool for identifying sleep disorders among Korean adults. Cutoff scores can help identify patients for sleep interventions. However, further large-scale studies are required to validate these findings.

Preparation of niacinamide imprinted starch-based biomaterials for treating of hyperpigmentation.

The aim of this study was to prepare niacinamide (NA) imprinted biomaterials for treating hyperpigmentation using mungbean starch (MS), PVA, and plasticizers (glycerol (GL) and citric acid (CA)). Biomaterials and NA were characterized by FE-SEM, FT-IR, and 1H NMR. To evaluate the applicability of the NA imprinted biomaterials for a transdermal drug delivery system (TDDS), NA release experiment was conducted in different pH and temperature conditions. Results of NA release properties indicated that NA was released about 99 % rapidly in the initial 10 min. NA release in low pH and high temperature was also higher than that in high pH and low temperature. The determination of experimental conditions and the analysis of NA release results were achieved using response surface methodology (RSM). Results of NA release using artificial skin indicated that NA release from NA imprinted biomaterials was increased at a relatively steady rate for 90 min. To verify for treating hyperpigmentation of the prepared biomaterials, tyrosinase inhibitory and antioxidant inhibitory were performed. Results indicated that NA imprinted biomaterials with the addition of CA exhibited 55.8 % of tyrosinase inhibitory and 73.0 % of antioxidant inhibitory. In addition, their ability to inhibit melanin synthesis in B16F10 cells was evaluated.

Translational Models in Glioma Immunotherapy Research.

Immunotherapy is a promising therapeutic domain for the treatment of gliomas. However, clinical trials of various immunotherapeutic modalities have not yielded significant improvements in patient survival. Preclinical models for glioma research should faithfully represent clinically observed features regarding glioma behavior, mutational load, tumor interactions with stromal cells, and immunosuppressive mechanisms. In this review, we dive into the common preclinical models used in glioma immunology, discuss their advantages and disadvantages, and highlight examples of their utilization in translational research.

The Pellino1-PKCθ Signaling Axis Is an Essential Target for Improving Antitumor CD8+ T-lymphocyte Function.

CD8+ T cells play an important role in the elimination of tumors. However, the underlying mechanisms involved in eliciting and maintaining effector responses in CD8+ T cells remain to be elucidated. Pellino1 (Peli1) is a receptor signal-responsive ubiquitin E3 ligase, which acts as a critical mediator for innate immunity. Here, we found that the risk of developing tumors was dependent on Peli1 expression. Peli1 was upregulated in CD8+ T cells among tumor-infiltrating lymphocytes (TIL). In contrast, a deficit of Peli1 enhanced the maintenance and effector function of CD8+ TILs. The development of Peli1-deficient CD8+ TILs prevented T-cell exhaustion and retained the hyperactivated states of T cells to eliminate tumors. We also found that Peli1 directly interacted with protein kinase C-theta (PKCθ), a central kinase in T-cell receptor downstream signal transduction, but whose role in tumor immunology remains unknown. Peli1 inhibited the PKCθ pathway by lysine 48-mediated ubiquitination degradation in CD8+ TILs. In summary, the Peli1-PKCθ signaling axis is a common inhibitory mechanism that prevents antitumor CD8+ T-cell function, and thus targeting Peli1 may be a useful therapeutic strategy for improving cytotoxic T-cell activity.

Enantioselective Acyloin Rearrangement of Acyclic Aldehydes Catalyzed by Chiral Oxazaborolidinium Ion.

A catalytic enantioselective acyloin rearrangement of acyclic aldehydes to synthesize highly optically active acyloin derivatives is described. In the presence of a chiral oxazaborolidinium ion catalyst, the reaction provided chiral α-hydroxy aryl ketones in high yield (up to 95%) and enantioselectivity (up to 98% ee). In addition, the enantioselective acyloin rearrangement of α,α-dialkyl-α-siloxy aldehydes produced chiral α-siloxy alkyl ketones in high yield (up to 92%) with good enantioselectivity (up to 89% ee).

Lactobacillus plantarum HAC01 Supplementation Improves Glycemic Control in Prediabetic Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial.

A recent animal study demonstrated that administration of Lactobacillus plantarum HAC01 isolated from Korean kimchi improved glycemic control in type 2 diabetic mice. In the present study, we evaluated Lactobacillus plantarum HAC01's effects on metabolic parameters of prediabetic human subjects. Forty subjects with isolated impaired glucose tolerance were randomly assigned to receive a daily placebo (n = 20) or a dose of Lactobacillus plantarum HAC01 (n = 20) over eight weeks. The primary endpoint was a change in 2 h postprandial glucose (2h-PPG) levels and the secondary endpoints were assessment of other glucose metabolism parameters, including HbA1c, gut microbiota composition, and fecal short-chain fatty acids (SCFAs). The group with a diet supplemented with Lactobacillus plantarum HAC01 saw a significant reduction in 2h-PPG and HbA1c levels compared to the placebo group. Fasting plasma glucose, insulin, HOMA-IR, QUICKI, microbiota composition, and fecal SCFAs, however, were not significantly altered. No serious adverse effects were reported. This is the first clinical trial to show a beneficial effect of single-strain probiotic supplementation administered over eight weeks on HbA1c levels in prediabetic subjects.

Pellino1 promotes chronic inflammatory skin disease via keratinocyte hyperproliferation and induction of the T helper 17 response.

Psoriasis is one of the most common immune-mediated chronic inflammatory skin diseases. However, little is known about the molecular mechanism underlying the immunological circuits that maintain innate and adaptive immune responses in established psoriasis. In this study, we found that the Pellino1 (Peli1) ubiquitin E3 ligase is activated by innate pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs), and is highly upregulated in human psoriatic skin lesions and murine psoriasis-like models. Increased Peli1 expression is strongly correlated with the immunopathogenesis of psoriasis by activating hyperproliferation of keratinocytes in the S and G2/M phases of the cell cycle and promoting chronic skin inflammation. Furthermore, Peli1-induced psoriasis-like lesions showed significant changes in the expression levels of several T helper 17 (Th17)-related cytokines, such as IL-17a, IL-21, IL-22, IL-23, and IL-24, indicating that overexpression of Peli1 resulted in the sequential engagement of the Th17 cell response. However, the overexpression of Peli1 in T cells was insufficient to trigger psoriasis, while T cells were indispensable for disease manifestation. In summary, our findings demonstrate that Peli1 is a critical cell cycle activator of innate immunity, which subsequently links Th17 cell immune responses to the psoriatic microenvironment.

Preparation and release properties of arbutin imprinted inulin/polyvinyl alcohol biomaterials.

The main objective of this work was to prepare inulin (INL)/polyvinyl alcohol (PVA) biomaterials imprinted with arbutin (AR) as the target drug. INL from Jerusalem artichoke flour was extracted with hot water extraction method. INL/PVA biomaterials were synthesized with a casting method and a UV curing. The optimal UV curing time and sodium benzoate content were about 10 min and 0.1 wt%, respectively. The biomaterials were characterized by SEM and FT-IR analysis. Mechanical properties of prepared AR imprinted biomaterials were also investigated. AR release was examined with changes of pH at 36.5 °C. The AR release ratio was also investigated using artificial skin. It was found that AR was released constantly for 40 min. Results of drug release mechanism indicated that AR release followed the Fickian diffusion behavior, whereas drug release using artificial skin followed the non-Fickian diffusion behavior. Tyrosinase inhibitory (%) for AR imprinted biomaterials with/without the addition of GL were 58.8% and 79.2%, respectively.

Mechanism of action of the trastuzumab biosimilar CT-P6.

Objectives: Therapeutic monoclonal antibody biosimilars are expected to help reduce the sizeable economic burden of targeted treatments. Trastuzumab (Herceptin®), a recombinant humanized monoclonal antibody that binds to the extracellular domain of HER2, is approved for use in HER2-overexpressing breast cancer (in both the adjuvant and metastatic settings) and HER2-positive gastric cancer. CT-P6 (Herzuma®) is a biosimilar of trastuzumab, designed to bind with high affinity and specificity to the same HER2 epitope as the reference product. We investigated whether CT-P6 exerts its effects through the same mechanism of action as trastuzumab. Methods: The mechanism of action of CT-P6 and trastuzumab, both as monotherapy and in combination with paclitaxel or pertuzumab, was compared in HER2-overexpressing breast cancer and gastric cancer cell models. Results: We confirmed that CT-P6 functions in a manner similar to trastuzumab by binding to the HER2 receptor, which is central to the effects of trastuzumab in all indications. Conclusions: Collectively, the results of this study show that the mechanisms of action of CT-P6 and trastuzumab are similar in HER2-positive breast cancer and gastric cancer models and, therefore, CT-P6 can be expected to perform similarly in the clinical setting.