Histopathologic image-based deep learning classifier for predicting platinum-based treatment responses in high-grade serous ovarian cancer.

Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image-based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model's decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.

An exploratory clinical trial of preoperative non-invasive localization before breast-conserving surgery using augmented reality technology.

PURPOSE: This single-center, randomized, prospective, exploratory clinical trial was conducted to assess the clinical efficacy of an augmented reality (AR)-based breast cancer localization imaging solution for patients with breast cancer. METHODS: This clinical trial enrolled 20 women who were diagnosed with invasive breast cancer between the ages of 19 and 80, had a single lesion with a diameter ≥ 5 mm but ≤ 30 mm, had no metastases to other organs, and had not received prior chemotherapy. All patients underwent mammography, ultrasound, computed tomography, and magnetic resonance imaging for preoperative assessment. Patients were randomly assigned to ultrasound-guided skin marking localization (USL) and AR-based localization (ARL) groups (n = 10 in each group). Statistical comparisons between USL and ARL groups were made based on demographics, radiologic features, pathological outcomes, and surgical outcomes using chi-square and Student t-tests. RESULTS: Two surgeons performed breast-conserving surgery on 20 patients. Histopathologic evaluation of all patients confirmed negative margins. Two independent pathologists evaluated the marginal distances, and there were no intergroup differences in the readers' estimates (R1, 6.20 ± 4.37 vs. 5.04 ± 3.47, P = 0.519; R2, 5.10 ± 4.31 vs. 4.10 ± 2.38, P = 0.970) or the readers' average values (5.65 ± 4.19 vs. 4.57 ± 2.84, P = 0.509). In comparing the tumor plane area ratio, there was no statistically significant difference between the two groups in terms of either reader's mean values (R1, 15.90 ± 9.52 vs. 19.38 ± 14.05, P = 0.525; R2, 15.32 ± 9.48 vs. 20.83 ± 12.85, P = 0.290) or the overall mean values of two readers combined (15.56 ± 9.11 vs. 20.09 ± 13.38, P = 0.388). Convenience, safety, satisfaction, and reusability were all superior in the AR localization group (P < 0.001) based on the two surgeons' responses. CONCLUSION: AR localization is an acceptable alternative to ultrasound-guided skin marking with no significant differences in surgical outcomes.

Tuning of chemical interface damping in single gold nanorods through pH-dependent host-guest interactions using cucurbit[6]uril.

Chemical interface damping (CID) in gold nanorods (AuNRs) arises from direct hot electron transfer from Au to adsorbed molecules. Despite recent studies on CID, its tunability in single AuNRs remains challenging. Herein, we present a method for in situ control of CID in single AuNRs using pH-dependent host-guest supramolecular interactions. We employ cucurbit[6]uril (CB[6]), a well-known host molecule capable of encapsulating and releasing guest molecules, along with bis(3-aminopropyl)amine (BAPA) as guest molecules forming a complex with CB[6] (CB[6]-BAPA). CID is induced by attaching the CB[6]-BAPA complex on AuNR surfaces through a strong Au-amine interaction. In addition, in situ tuning of CID is achieved by releasing CB[6] from the complex using a NaOH solution. Successful CB[6]-BAPA complex formation, their attachment onto AuNRs, and CB[6] release from the complex are confirmed through changes in the localized surface plasmon resonance (LSPR) peak and LSPR linewidth, alongside mass analysis. Therefore, this study offers a new method for in situ CID tuning using CB[6]-based pH-sensitive host-guest interactions in individual AuNRs. This study can be further used in CB[6]-based photochemical processes and biosensing studies.

Three cycles of mobile app design to improve HIV self-management: A development and evaluation study.

Objective: Employing three cycles of Design Science Research (DSR) to develop a mobile app 'ESSC (Excellent Self Supervised HIV Care)' to improve self-management among people living with HIV (PLWH). Methods: This study is based on the DSR framework comprising three iterative cycles. In the Relevance cycle, PLWH participated in a survey of mobile health (mHealth) experiences and needs. In the Rigor cycle, the information-motivation-behavioural skills (IMB) model was applied to foundations of the app, and HIV specialists verified the contents. Experts evaluated the heuristic system and the app quality with the Mobile Application Rating Scale (MARS). In the Design cycle, ESSC was built on the findings of the other two cycles, and end-users tested the usability using uMARS. Results: The contents of the app were developed based on user requirements. The IMB model led ESSC to supplement motivational components for self-management, which built five functions: information contents; health life records including mental and sexual health; interactive counselling with healthcare providers; setting health goals after watching videos; and my page for self-reflection. To reduce social stigma and promote acceptance of the information-driven app, we created animated characters with neutral and bright features. The HIV specialists evaluated content validity as highly appropriate. The MARS score by the overall raters was between 3-acceptable and 4-good: functionality, 4.38; information, 4.12; aesthetics, 3.96; engagement, 3.37; and subjective quality, 3.25. Conclusions: The DSR approach is effective for implementing usable and useful mHealth. The ESSC app would be feasible and contribute PLWH to retention in care.

Distinct effects of rosuvastatin and rosuvastatin/ezetimibe on senescence markers of CD8+ T cells in patients with type 2 diabetes mellitus: a randomized controlled trial.

Objectives: Chronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to ß-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin/ezetimibe combination treatment on T cell senescence markers. Methods: In this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication. Results: The fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (Treg) significantly decreased after intervention in the rosuvastatin/ezetimibe group (-4.5 ± 14.1% and -1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, p=0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, p=0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c (p=0.314) or LDL-C (p=0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group (p=0.011), but not in the rosuvastatin group (p=0.339). Conclusions: We observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels.

Initial experience with the enhanced recovery after surgery (ERAS) protocols in gynecologic surgery at an urban academic tertiary medical center.

Background: The enhanced recovery after surgery (ERAS) protocols have been consistently associated with improved patient experience and surgical outcomes. Despite the release of ERAS Society guidelines specific to gynecologic oncology, the adoption of ERAS in gynecology on global level has been disappointingly low and some centers have shown minimal improvement in clinical outcomes after adopting ERAS. The aim of this study is to describe the development and early experience of ERAS protocols in gynecologic surgery at an urban academic tertiary medical center. Methods: This was an observational prospective cohort study. The target patient population included those with low comorbidities who were scheduled to undergo various types of gynecologic surgeries for both benign and malignant diseases between October 2020 and February 2021. Two attending surgeons implemented the protocols for their patients (ERAS cohort) while three attending surgeons maintained the conventional perioperative care for their patients (non-ERAS cohort). Baseline characteristics, surgical outcomes and patients' answers to a 12-question survey were compared. A case-matched comparative analysis was also performed between the ERAS cohort and the historical non-ERAS cohort (those who received the same types of surgical procedures from the two ERAS attending surgeons prior to the implementation of the protocols). Results: A total of 244 patients were evaluated (122 in the ERAS cohort vs. 122 in the non-ERAS cohort). The number of vials of opioid analgesia used during the first two postoperative days was significantly lower whereas the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen was more frequent in the ERAS cohort group. The patients in the ERAS group reported less postoperative pain, feelings of hunger and thirst, and greater amount of exercise postoperatively. These benefits of the ERAS cohort were more pronounced in the patients who underwent laparotomic surgeries than those who underwent laparoscopic surgeries. The case-matched comparative analysis also showed similar results. The length of hospital stay did not differ between those who underwent the ERAS protocols and those who did not. Conclusions: The results of the study demonstrated the safety, clinical feasibility and benefits of the ERAS protocols for patients undergoing gynecologic surgeries for both benign and malignant indications.

Comparative Efficacy of Rosuvastatin Monotherapy and Rosuvastatin/Ezetimibe Combination Therapy on Insulin Sensitivity and Vascular Inflammatory Response in Patients with Type 2 Diabetes Mellitus.

BACKGRUOUND: Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM. METHODS: A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment. RESULTS: The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups. CONCLUSION: Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Does Bladder Cancer Subtype Influence Pathologic Complete Response (pCR) and Pelvic Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Response Evaluation After Neoadjuvant Chemotherapy? Pathological Perspective.

INTRODUCTION: We aimed to provide a pathological perspective on the management of muscle-invasive bladder cancer (MIBC) by correlating the prechemotherapy transurethral resection of bladder tumor findings and postchemotherapy radiologic evaluation with final radical cystectomy (RC) findings. MATERIALS AND METHODS: This retrospective study included 79 MIBC patients treated with neoadjuvant chemotherapy (NAC) and RC. Pelvic diffusion-weighted magnetic resonance imaging (DW-MRI) and pathologic reports were retrieved from our institutional database. All pathology slides were reviewed based on diagnostic criteria with high interobserver reproducibility. RESULTS: Pathologic complete response (pCR) was confirmed in 32 patients (40.5%). The concordance and discordance between MRI and RC findings occurred in 68.3% and 31.7% of cases, respectively. The 21.5% of cases that were clinical CR (cCR) on MRI actually achieved pCR on RC specimens and 46.8% of cases that were non-cCR on MRI were actually non-pCR on RC specimens. In 19.0% of cases, RC findings were pCR, but MRI demonstrated residual tumor and the opposite was 12.7%. The greatest discrepancy between the 2 methods (75%, 3/4) was for the plasmacytoid subtype. Plasmacytoid histology was the most common histological subtype identified in RC specimens after NAC, followed by micropapillary and squamous histologies. CONCLUSIONS: We found that all cases with plasmacytoid and micropapillary subtypes, and squamous differentiation did not show pCR. In particular, the largest discrepancy between MRI findings and RC pathology after NAC was seen in the plasmacytoid subtype. An accurate pathologic diagnosis based on strict criteria to identify histological subtypes of MIBC is necessary for proper treatment.

Soybean Variety Saedanbaek Confers a New Resistance Allele to Phytophthora sojae.

Phytophthora root and stem rot (PRSR) disease results in substantial losses in soybean production worldwide. The occurrence of PRSR caused by Phytophthora sojae Kaufmann & Gerdemann has become increasingly important for soybean production in the Republic of Korea, but domestic soybean-P. sojae interaction has been less studied. The disease has been managed by developing varieties harboring resistance to the Phytophthora sojae (Rps) gene. The present study aimed to identify a major gene locus conferring resistance to new P. sojae isolate 2858 in the recombinant inbred line population derived from a cross between parental lines 'Daepung' (susceptible) and 'Saedanbaek' (resistant). Seventy-three recombination inbred lines (RILs) were evaluated for resistance to P. sojae isolate 2858. A resistance locus was identified in the approximate 3.3-4.3 megabase pair region on chromosome 3 using both single-marker and linkage analyses. The Rps of Saedanbaek (RpsSDB) was located on the well-known Rps gene/allele cluster region, which also partially overlapped with a locus previously identified in the Korean soybean variety, 'Daewon', resistant to another P. sojae isolate 2457 (RpsDW). Approximately 402 kilobase pairs of the interval region overlapped, including six nucleotide-binding site-leucine-rich repeat (NBS-LRR)-coding genes. Additional phenotypic assays revealed that Saedanbaek was susceptible to isolate 2457 and that Daewon was susceptible to isolate 2858, indicating that RpsSDB and RpsDW are different genes or alleles that confer race-specific resistance to the two P. sojae isolates. These results provide information that will be helpful for breeders developing P. sojae-resistant cultivars.

GCSB-5 regulates inflammatory arthritis and pain by modulating the mitogen-activated protein kinase signaling pathway in a murine model of rheumatoid arthritis.

Objectives: This study aimed to determine whether GCSB-5 has anti-inflammatory and antinociceptive effects in mice with collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis (RA), and investigate the influence of GCSB-5 on the mitogen-activated protein kinase (MAPK) pathway. Materials and methods: The experimental animal study was designed to include five groups: CIA mice treated with GCSB-5 (300 mg/kg), GCSB-5 (600 mg/kg), celecoxib (60 mg/kg), or saline for four weeks, and nontreated control mice. The clinical severity of arthritis was scored. Nociceptive thresholds were measured by using a von Frey dynamic plantar analgesimeter. The MAPK pathway was evaluated in mouse synovium. The expression of channels associated with pain signaling was assessed by western blot and immunohistochemical staining. Results: GCSB-5 treatment diminished the severity of clinical arthritis and increased the nociceptive threshold in mice with CIA. Celecoxib, a positive control drug, also showed comparable changes. Clinical arthritis scores were inversely related to mechanical thresholds. GCSB-5 administration decreased the levels of anti-type II collagen antibody and inflammatory cytokines in the sera of mice with CIA. Furthermore, ERK, p38 MAPK, and JNK phosphorylation were downregulated and TRPV1 and ASIC3 expression were decreased in the synovium of GCSB-5-treated mice compared to salinetreated mice. Interleukin-6-induced TRPV1 and ASIC3 upregulation were also inhibited by GCSB-5 in human RA fibroblast-like synoviocytes in vitro. Conclusion: GCSB-5 decreased inflammatory arthritis and pain in a murine model of RA. The results present evidence that GCSB-5 may be beneficial for relieving pain as well as decreasing inflammation in autoimmune arthritis, such as RA.

Anti-Inflammatory Effect of Cinnamomum japonicum Siebold's Leaf through the Inhibition of p38/JNK/AP-1 Signaling.

Cinnamomum japonicum Siebold (CJ) branch bark, commonly known as Japanese cinnamon, has been used for various culinary and medicinal applications for many centuries. Although the efficacy of CJ branch bark's anti-inflammatory and antioxidant activity for the treatment of various diseases has been confirmed, the efficacy of CJ leaves (CJLs) has not been examined. We therefore investigated whether CJL3, an ethyl acetate extract of a 70% ethanol CJL extract, exerts anti-inflammatory effects on lipopolysaccharide (LPS)-activated Kupffer cells, specialized macrophages found in the liver. Liver inflammation can activate Kupffer cells, inducing the release of pro-inflammatory molecules that contribute to tissue damage. We found that CJL3 has high 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) radical-scavenging activity. Among the CJL extracts, CJL3 exhibited the greatest polyphenol content, with protocatechuic acid and 4-hydroxybenzoic acid being the most abundant. In addition, we verified that CJL3, which has strong antioxidant properties, ameliorates LPS-induced pro-inflammatory responses by inhibiting p38/JNK/AP-1 signaling. CJL3 therefore has potential for treating liver disease, including hepatitis.

Invasive urothelial carcinoma with chordoid features or abundant myxoid stroma: A reappraisal of morphologic spectrum and risk stratification based on molecular classification.

Urothelial carcinoma (UC) with myxoid stroma or chordoid features is a rare diagnosis. We retrospectively collected data from 17 cases of diagnosed UC with myxoid stroma, mucin production, or chordoid features. We aimed to investigate the molecular subtypes of this neoplasm and to assess subtype correlations with clinical outcomes. Immunohistochemical (IHC) staining with a panel composed of markers for basal subtypes (CK5/6, CK14, and CD44) and luminal subtypes (GATA3, FOXA1, and CK20) was performed. Morphologically, all cases included an at least partial conventional UC component, with the first histologic pattern, named as "typical", characterized by a small- or medium-sized tumor cell nest. The second histologic pattern, named as "chordoid", was characterized by tumor cells with cording that mimic extra-skeletal myxoid chondrosarcoma or chordoma, and the third histologic pattern, named as "sarcomatoid", was characterized by non-cohesive spindle tumor cells with a mucin-producing or myxoid stroma background. The "typical" cases showed [CK5/6- CK14- CD44-] [GATA3 + FOXA1 + CK20-] IHC results and was classified as lumina subtype. The "chordoid" cases showed [CK5/6 + CK14 + CD44-] [GATA3- FOXA1- CK20-] IHC results and was classified as basal subtype, and the "sarcomatoid" cases showed [CK5/6- CK14- CD44+] [GATA3- FOXA1- CK20-] IHC results and was "not classified". All pT3 cases and all cases with lymph node (LN) metastasis belonged to the "sarcomatoid" pattern. All patients who had metastasis or died showed the "chordoid" or "sarcomatoid" morphology. Our findings suggest that UC with myxoid stroma/chordoid features shows characteristic expression of luminal and basal markers and different prognosis according to the morphologic pattern spectrum.

OR2H2 Activates CAMKKß-AMPK-Autophagy Signaling Axis and Suppresses Senescence in VK2/E6E7 Cells.

Olfactory receptors are expressed in multiple extra-nasal tissues and these ectopic olfactory receptors mediate tissue-specific functions and regulate cellular physiology. Ectopic olfactory receptors may play key roles in tissues constantly exposed to odorants, thus the functionality of these receptors in genital tissues is of particular interest. The functionality of ectopic olfactory receptors expressed in VK2/E6E7 human vaginal epithelial cells was investigated. OR2H2 was the most highly expressed olfactory receptor expressed in VK2/E6E7 cells, and activation of OR2H2 by aldehyde 13-13, a ligand of OR2H2, increased the intracellular calcium and cAMP concentrations. Immunoblotting demonstrated that activation of OR2H2 by aldehyde 13-13 stimulated the CAMKKß-AMPK-mTORC1-autophagy signaling axis, and that these effects were negated by OR2H2 knockdown. AMPK is known to regulate senescence; consequently, we investigated further the effect of aldehyde 13-13 on senescence. In H2O2-induced senescent cells, activation of OR2H2 by aldehyde 13-13 restored proliferation, and reduced the expression of senescence markers, P16 and P19. Additionally, aldehyde 13-13 induced apoptosis of H2O2-induced senescent cells, compared with non-senescent normal cells. In vivo, aldehyde 13-13 increased the lifespan of Caenorhabditis elegans and budding yeast. These findings demonstrate that OR2H2 is a functional receptor in VK2/E6E7 cells, and that activation of OR2H2 activates the AMPK-autophagy axis, and suppresses cellular aging and senescence, which may increase cellular health.

The complete mitochondrial genome of Helicana japonica (Crustacea, Decapoda, Varunidae) from South Korea.

Helicana japonica mainly inhabits burrowed holes in the mudflats and intertidal zones. Specimens from the Republic of Korea were collected and whole genomic DNA from the cheliped muscle tissue was extracted. We determined the complete mitochondrial genome using Illumina HiSeq X Ten. The mitogenome is 16,535 bp in length and consists of 13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes. A phylogenetic tree was reconstructed using the maximum-likelihood of phylogeny methods. H. japonica formed a sister clade with Helicana wuana, which is another Helicana species.

Application of The Paris System in neobladder washing cytology: Comparison between the original diagnosis and correlation with histopathology.

BACKGROUND: In urinary diversion after radical cystectomy, the incidence of recurrent urothelial carcinoma (UC) in upper urinary tract or urethra are reported in 2%-17% of the patients. Urine cytology plays a pivotal role in detecting the recurrence of UC. However, cytologic diagnosis in urinary diversion including neobladder is often challenging due to significant degenerative changes and necro-inflammatory background. Since the proposal of The Paris System (TPS) for reporting cytology, the utility of TPS in urinary diversion specimen has not been studied yet. The objective of this study is to evaluate the diagnostic usefulness of TPS compared with the original diagnosis and correlate with the matched histopathological results. METHODS: Urinary diversion cytology specimens with concurrent or subsequent biopsy or resection at EUMC in recent 16 years (from January 2002 to December 2018) are retrospectively reviewed and reclassified according to TPS criteria. The TPS categories and the original diagnoses were compared and correlated with follow-up histology. RESULTS: Concurrent or subsequent biopsy or resection within a 6-month period was available in 45 cases from 28 patients. When applying TPS, the rate of atypical and suspicious categories decreased by 13.4% and 11.1%. Using TPS increased the value of sensitivity, NPV, and accuracy to 93.75%, 93.75%, and 90.91%, respectively. CONCLUSION: Application of TPS reduced the rate of indeterminate diagnoses and moreover, improved the sensitivity and accuracy of urinary diversion cytology. Therefore, we believe that diversion urine cytology diagnosis according to TPS is useful to screen patients for detection of recurrence in routine clinical practice.

Proliferation-Related Features of the Human Mesenchymal Stem Cells Derived from Palatine Tonsils, Adipose Tissues, and Bone Marrow.

BACKGROUND: Mesenchymal stem cells (MSCs) are widely used in regenerative medicine and cell-based transplantations. However, an in-depth comparison of the different MSC origins is lacking. This study aimed to compare the expression of adipose-derived (AMSCs), bone marrow-derived (BMSCs), and tonsil-derived (TMSCs) and evaluate whether TMSCs are good alternatives for AMSCs or BMSCs. METHODS: We analyzed the expression levels of 47,000 transcripts in AMSCs (n = 4), BMSCs (n = 4), and TMSCs (n = 4) using GeneChip. Microarray data were analyzed using the LIMMA package to compare the TMSCs, AMSCs, and BMSCs. Hub genes were analyzed using STRING and Cytoscape. To ascertain the functional roles of AURKA and AURKB, small interfering RNA (siRNA) molecules specifically targeting AURKA and AURKB mRNA were synthesized and employed to induce knockdown of AURKA and AURKB in TMSC and AMSC. We analyzed the expression level of OCT4, SOX-2, and NANOG genes in TMSC and AMSCs by cell culture and real-time PCR. RESULTS: We identified commonly increased 256 and decreased 160 genes in TMSCs from the differentially expressed genes (DEGs) between the TMSCs, AMSCs, and BMSCs. In the DEG-based protein-protein interaction and gene set enrichment analysis, hub genes (AURKA, AURKB, CDC20, and BUB1) highly expressed in TMSCs were enriched for development- and progression-related oocyte meiosis, the cell cycle, and ubiquitin-mediated proteolysis. In vitro analysis demonstrated that cells with downregulated expression of AURKA and AURKB exhibited a significant reduction in proliferation compared to control cells. However, silencing of the genes did not affect the differentiation capacity in TMSCs and AMSCs. CONCLUSION: Our study compared MSCs of different origins to better understand the similarities and differences among these cell types.

Effect of deferoxamine and ferrostatin-1 on salivary gland dysfunction in ovariectomized rats.

The mechanism underlying xerostomia after menopause has not yet been fully elucidated. This study aimed to investigate the mechanism of xerostomia and the effect of the ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (FER) on salivary gland dysfunction in a postmenopausal animal model. Twenty-four female Sprague-Dawley rats were randomly divided into four groups: a SHAM group (n = 6, sham-operated rats), an OVX group (n = 6, ovariectomized rats), an FER group (n = 6, ovariectomized rats injected intraperitoneally with FER), and a DFO group (n = 6, ovariectomized rats injected intraperitoneally with DFO). GPX4 activity, iron accumulation, lipid peroxidation, inflammation, fibrosis, and salivary gland function were analyzed. Recovery of GPX4 activity and a decrease in iron accumulation and cytosolic MDA + HAE were observed in the DFO group. In addition, collagen I, collagen III, TGF-ß, IL-6, TNF-α, and TGF-ß levels were decreased in the DFO group compared to the OVX group. Recovery of GPX4 activity and the morphology of mitochondria, and reduction of cytosolic MDA + HAE were also observed in the FER group. In addition, decreased expression of inflammatory cytokines and fibrosis markers and increased expression of AQP5 were observed in both the DFO and FER groups. Postmenopausal salivary gland dysfunction is associated with ferroptosis, and DFO and FER may reverse the postmenopausal salivary gland dysfunction after menopause. DFO and FER are hence considered promising treatments for postmenopausal xerostomia.

Synbiotic Fermentation of Undaria pinnatifida and Lactobacillus brevis to Produce Prebiotics and Probiotics.

It has been optimized thermal acid hydrolytic pretreatment and enzymatic saccharification (Es) in flask culture of Undaria pinnatifida seaweed, which is a prebiotic. The optimal hydrolytic conditions were a slurry content of 8% (w/v), 180 mM H2SO4, and 121°C for 30 min. Es using Celluclast 1.5 L at 8 U/mL produced 2.7 g/L glucose with an efficiency of 96.2%. The concentration of fucose (a prebiotic) was 0.48 g/L after pretreatment and saccharification. The fucose concentration decreased slightly during fermentation. Monosodium glutamate (MSG) (3%, w/v) and pyridoxal 5'-phosphate (PLP) (30 µM) were added to enhance gamma-aminobutyric acid (GABA) production. To further improve the consumption of mixed monosaccharides, adaptation of Lactobacillus brevis KCL010 to high concentrations of mannitol improved the synbiotic fermentation efficiency of U. pinnatifida hydrolysates.