Non-thermal atmospheric pressure plasma-conditioned root dentin promotes attraction and attachment of primary human dental pulp stem cells in real-time Ex Vivo

This study investigated if non-thermal atmospheric pressure plasma (NTAPP) treatment of root dentin surfaces promotes human dental pulp stem cell (hDPSCs) adhesion. Freshly extracted human single-rooted teeth (n = 36) were decoronated and cut (first vertically, then horizontally) into root dentin slices (3 mm thick). Primary hDPSCs cultures were seeded onto slices randomly assigned to pretreatment groups (n = 9/group): NaOCl (1.5%), EDTA (17%) then NTAPP (Group I); NaOCl then NTAPP (Group II); NaOCl then EDTA (Group III); and NaOCl alone (Group IV). Cell viability and proliferation were measured using MTT assay with log-linear statistical analysis. Cell attachment and spreading morphologies on dentin slices (n = 3/group) were examined through scanning electron microscopy. Early cell adhesion events and subcellular activities were observed in real time by live-cell imaging through holotomographic microscopy. Cell viability and proliferation were significantly higher on NTAPP-treated dentin (p \u3c 0.05), without interactions with EDTA (p \u3e 0.05). The attachment, spreading, extensions and multiple layers of hDPSCs were heightened on NTAPP-treated dentin. Cell adhesion, spreading, and dentinal tubule penetration were hastened on NTAPP-treated dentin surfaces in real-time, with elevated subcellular activities and intracellular lipid droplet formation. NTAPP-treated root dentin surfaces support enhanced cellular responses, potentially promoting pulp-dentin regeneration

TGF-beta has paradoxical and context dependent effects on proliferation and anoikis in human colorectal cancer cell lines.

Transforming growth factor-beta (TGF-beta) is a pluripotent cytokine that can have both tumor suppressing and tumor promoting effects on epithelial cells. It is unclear what determines when TGF-beta and its signaling pathway act predominantly as a tumor suppressor pathway or as a tumor-promoter pathway and whether TGF-beta can have both classes of effects concurrently on a cell. We investigated the effect of TGF-beta on anoikis in colorectal cancer cell lines sensitive to TGF-beta-mediated growth inhibition to determine if the context of the cells could be one of the factors that would affect whether TGF-beta exerts tumor suppressor or oncogene activity on colon cancer cells. We observed variable effects of TGF-beta on anoikis in these cell lines, even though they all are growth-inhibited by TGF-beta. Thus, we show that TGF-beta has variable effects on anoikis in colon cancer cell lines that likely reflects the effects of concurrent gene mutations in the cancer cells and the activation state of the signaling pathways controlled by these genes

Geriatric Medicine in South Korea: A Stagnant Reality amidst an Aging Population

In the face of an ever-increasing wave of an aging population, this paper provides an update on the current status of geriatric medicine in Korea, comparing it with global initiatives and suggesting future directions. Older adults require a multifaceted approach, addressing not only comorbidity management but also unmet complex medical needs, nutrition, and exercise to prevent functional decline. In this regard, the World Health Organization's Integrated Care for Older People guidelines underscore the importance of patient-centered primary care in preventing a decline in intrinsic capacity. Despite these societal needs and the ongoing aging process, the healthcare system in Korea has yet to show significant movement or a shift toward geriatric medicine, further complicated by the absence of a primary care system. We further explore global efforts in establishing age-integrative patient-centered medical systems in Singapore, Australia, Canada, the United Kingdom, and Japan. Additionally, we review the unmet needs and social issues that Korean society is currently facing, and local efforts by both government and a private tertiary hospital in Korea. In conclusion, considering the current situation, we propose that the framework of geriatric medicine should form the foundation of the future healthcare system

APE1 Promotes Pancreatic Cancer Proliferation through GFRα1/Src/ERK Axis-Cascade Signaling in Response to GDNF

Pancreatic cancer is the worst exocrine gastrointestinal cancer leading to the highest mortality. Recent studies reported that aberrant expression of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is involved in uncontrolled cell growth. However, the molecular mechanism of APE1 biological role remains unrevealed in pancreatic cancer progression. Here, we demonstrate that APE1 accelerates pancreatic cancer cell proliferation through glial cell line-derived neurotrophic factor (GDNF)/glial factor receptor α1 (GFRα1)/Src/ERK axis-cascade signaling. The proliferation of endogenous APE1 expressed-MIA PaCa-2, a human pancreatic carcinoma cell line, was increased by treatment with GDNF, a ligand of GFRα1. Either of downregulated APE1 or GFRα1 expression using small interference RNA (siRNA) inhibited GDNF-induced cancer cell proliferation. The MEK-1 inhibitor PD98059 decreased GDNF-induced MIA PaCa-2 cell proliferation. Src inactivation by either its siRNA or Src inhibitor decreased ERK-phosphorylation in response to GDNF in MIA PaCa-2 cells. Overexpression of GFRα1 in APE1-deficient MIA PaCa-2 cells activated the phosphorylation of Src and ERK. The expression of both APE1 and GFRα1 was gradually increased as progressing pancreatic cancer grades. Our results highlight a critical role for APE1 in GDNF-induced pancreatic cancer cell proliferation through APE1/GFRα1/Src/ERK axis-cascade signaling and provide evidence for future potential therapeutic drug targets for the treatment of pancreatic cancer

Effect of donor–recipient size mismatch on long-term graft survival in pediatric kidney transplantation: a multicenter cohort study

Background Donor–recipient size mismatching is commonly occurs in pediatric kidney transplantation (KT). However, its effect on graft survival remains unknown. This study aimed to determine the effect of donor–recipient size mismatch on the long-term survival rate of transplant kidneys in pediatric KT. Methods A total of 241 pediatric patients who received KT were enrolled. The medical records of all patients were retrospectively reviewed, and the correlation between donor–recipient size mismatch and graft function and long-term graft outcome was analyzed according to donor–recipient size mismatch. Results Recipients and donors’ mean body weight at the time of KT were 34.31 ± 16.85 and 56.53 ± 16.73 kg, respectively. The mean follow-up duration was 96.49 ± 52.98 months. A significant positive correlation was observed between donor–recipient body weight ratio (DRBWR) or donor–recipient body surface area ratio (DRBSR) and graft function until 1 year after KT. However, this correlation could not be confirmed at the last follow-up. The results of long-term survival analysis using Fine and Gray’s subdistribution hazard model showed no significant difference of the survival rate of the transplant kidney according to DRBWR or DRBSR. Conclusion Donor–recipient size mismatch in pediatric KT is not an important factor in determining the long-term prognosis of transplant kidneys

The Clinical Frailty Scale as a Risk Assessment Tool for Dysphagia in Older Inpatients: A Cross-Sectional Study

Background Dysphagia is a common problem with potentially serious consequences including malnutrition, dehydration, pneumonia, and death. However, there are challenges in screening for dysphagia in older adults. We assessed the feasibility of using the Clinical Frailty Scale (CFS) as a risk assessment tool for dysphagia. Methods This cross-sectional study was conducted at a tertiary teaching hospital from November 2021 to May 2022 and included 131 older patients (age ≥65 years) admitted to acute wards. We used the Eating Assessment Tool-10 (EAT-10), which is a simple measure for identifying individuals at risk of dysphagia, to assess the relationship between EAT-10 score and frailty status as measured using the CFS. Results The mean age of the participants was 74.3±6.7 years, and 44.3% were male. Twenty-nine (22.1%) participants had an EAT-10 score ≥3. The CFS was significantly associated with an EAT-10 score ≥3 after adjusting for age and sex (odds ratio=1.48; 95% confidence interval [CI], 1.09–2.02). The CFS was able to classify the presence of an EAT-10 score ≥3 (area under the receiver operating characteristic [ROC] curve=0.650; 95% CI, 0. 544–0.756). The cutoff point for predicting an EAT-10 score ≥3 was a CFS of 5 according to the highest Youden index, with a sensitivity of 82.8% and a specificity of 46.1%. The positive and negative predictive values were 30.4% and 90.4%, respectively. Conclusion The CFS can be used as a tool to screen for the risk of swallowing difficulty in older inpatients to determine clinical management encompassing drug administration routes, nutritional support, prevention of dehydration, and further evaluation of dysphagia

Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes

<p>Abstract</p> <p>Background</p> <p>Phosphatidylcholine (PPC) formulation is used for lipolytic injection, even though its mechanism of action is not well understood.</p> <p>Methods</p> <p>The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD), and a PPC formulation. Western blot analysis was performed to examine PPC-induced signaling pathways.</p> <p>Results</p> <p>PPC, SD, and PPC formulation significantly decreased 3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not cytotoxic to CCD-25Sk human fibroblasts at concentrations <1 mg/ml, whereas SD and PPC formulation were cytotoxic. Western blot analysis demonstrated that PPC alone led to the phosphorylation of the stress signaling proteins, such as p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and activated caspase-9, -8, -3 as well as cleavage of poly(ADP-ribose) polymerase. However, SD did not activate the apoptotic pathways. Instead, SD and PPC formulation induced cell membrane lysis, which may lead to necrosis of cells.</p> <p>Conclusions</p> <p>PPC results in apoptosis of 3T3-L1 cells.</p

Development of a Spirometry \u3cem\u3eT\u3c/em\u3e-score in the General Population

Background and objective: Spirometry values may be expressed as T-scores in standard deviation units relative to a reference in a young, normal population as an analogy to the T-score for bone mineral density. This study was performed to develop the spirometry T-score. Methods: T-scores were calculated from lambda-mu-sigma-derived Z-scores using a young, normal age reference. Three outcomes of all-cause death, respiratory death, and COPD death were evaluated in 9,101 US subjects followed for 10 years; an outcome of COPD-related health care utilization (COPD utilization) was evaluated in 1,894 Korean subjects followed for 4 years. Results: The probability of all-cause death appeared to remain nearly zero until -1 of forced expiratory volume in 1 second (FEV1) T-score but increased steeply where FEV1 T-score reached below -2.5. Survival curves for all-cause death, respiratory death, COPD death, and COPD utilization differed significantly among the groups when stratified by FEV1 T-score (P \u3c 0.001). The adjusted hazard ratios of the FEV1 T-score for the four outcomes were 0.54 (95% confidence interval, 0.48–0.60), 0.43 (95% CI: 0.37–0.50), 0.30 (95% CI: 0.24–0.37), and 0.69 (95% CI: 0.59–0.81), respectively, adjusting for covariates (P \u3c 0.001). Conclusion: The spirometry T-score could predict all-cause death, respiratory death, COPD death, and COPD utilization

Clinical risk factors associated with the development of wheezing in children less than 2 years of age who required hospitalization for viral lower respiratory tract infections

PurposeWheezing following viral lower respiratory tract infections (LRTIs) in children <2 years of age is an important risk factor for the development of asthma later in life; however, not all children with viral LRTIs develop wheezing. This study investigated risk factors for the development of wheezing during viral LRTIs requiring hospitalization.MethodsThe study included 142 children <2 years of age hospitalized for LRTIs with at least one virus identified as the cause and classified them into children diagnosed with LRTIs with wheezing (n=70) and those diagnosed with LRTIs without wheezing (n=72).ResultsThere were no significant differences in the viruses detected between the two groups. Multivariate logistic regression analysis showed that, after adjusting for potentially confounding variables including sex and age, the development of wheezing was strongly associated with parental history of allergic diseases (adjusted odds ratio [aOR], 20.19; 95% confidence interval [CI], 3.22-126.48), past history of allergic diseases (aOR, 13.95; 95% CI, 1.34-145.06), past history of hospitalization for respiratory illnesses (aOR, 21.36; 95% CI, 3.77-120.88), exposure to secondhand smoke at home (aOR, 14.45; 95% CI, 4.74-44.07), and total eosinophil count (aOR, 1.01; 95% CI, 1.01-1.02).ConclusionPast and parental history of allergic diseases, past history of hospitalization for respiratory illnesses, exposure to secondhand smoke at home, and total eosinophil count were closely associated with the development of wheezing in children <2 years of age who required hospitalization for viral LRTIs. Clinicians should take these factors into consideration when treating, counseling, and monitoring young children admitted for viral LRTIs