Antioxidant Activities in Kenaf (Hibiscus cannabinus) Shoots during Growth Stages and Destination of Chlorogenic Acid and Kaempferol Glycosides.

Apart from being utilized as a commercial fiber at maturity, kenaf shoots have potential as a food and feed source because of their diverse bioactivities. Previous studies have focused on mature stems because of their high biomass, whereas the antioxidant activities (AA) and the destination of AA contributors of kenaf stems and their high-yielding byproduct leaves during the growth stage have rarely been studied. Therefore, we investigated changes in AA and its relative components in kenaf leaves and stems during the four vital growth stages. Higher ABTS radical cation and DPPH radical scavenging abilities and ferric reducing antioxidant power, total phenolic content, total flavonoid content, and total polysaccharide content were observed at all leaf stages and in the late stem stages. Chlorogenic acid (CGA) and kaempferol glycosides, especially kaempferitrin (Kfr), were identified as representative phenolic acids and flavonoids in both kenaf leaves and stems. The content of CGA in both leaves and stems increased corresponding to the plant's growth stage, whereas kaempferol glycosides were enhanced in leaves but declined in stems. The highest correlation was observed between TPC and AA in all organs. Further evaluation of CGA and Kfr verified that CGA was the predominant contributor to AA, surpassing Kfr. These findings suggest that kenaf leaves increase antioxidant levels as they grow and can be a useful source of stem harvesting byproducts.

Evaluating the Association of Obesity and Chronic Rhinosinusitis: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this Meta-analysis and systematic review was to perform a comprehensive assessment of the association of chronic rhinosinusitis (CRS) with overweight/obesity, leptin hormone, and its associated metabolic dysregulation. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, were searched for studies from 1946 to October 2022, using predefined syntax. REVIEW METHODS: Outcome data for the meta-analysis were extracted on odds ratios (OR) of CRS prevalence based on the presence of overweight/obesity and mean serum leptin levels. A Meta-analysis was performed using the DerSimonian-Laird estimator to pool extracted data by the generalized inverse variance approach. Random effect models were utilized due to the small sample size. A qualitative synthesis was performed on articles that did not meet the inclusion criteria for the Meta-analysis. RESULTS: Thirty-six studies met the systematic review inclusion criteria out of 1113 articles screened. A total of 6 studies were included in the pooled Meta-analysis of the various outcome variables. Our pooled meta-analysis observed a positive association between overweight/obesity and the prevalence of CRS (OR = 1.33, 95% confidence interval [CI]: 1.17-1.51). The pooled ratio of the means analysis of the mean serum leptin levels between CRS with nasal polyposis and control patients was 2.21 (95% CI: 1.45; 3.36). CONCLUSION: Our pooled Meta-analysis indicates a positive association between overweight/obesity and CRS. Future prospective studies are needed to explore the association between CRS and obesity with an understanding of potential confounding comorbidities, including studies focused on assessing the underlying immunologic mechanism of this association.

Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that-in the case of the interdependent tumor cell morphology and adapted immune response-reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.

adaPop: Bayesian inference of dependent population dynamics in coalescent models.

The coalescent is a powerful statistical framework that allows us to infer past population dynamics leveraging the ancestral relationships reconstructed from sampled molecular sequence data. In many biomedical applications, such as in the study of infectious diseases, cell development, and tumorgenesis, several distinct populations share evolutionary history and therefore become dependent. The inference of such dependence is a highly important, yet a challenging problem. With advances in sequencing technologies, we are well positioned to exploit the wealth of high-resolution biological data for tackling this problem. Here, we present adaPop, a probabilistic model to estimate past population dynamics of dependent populations and to quantify their degree of dependence. An essential feature of our approach is the ability to track the time-varying association between the populations while making minimal assumptions on their functional shapes via Markov random field priors. We provide nonparametric estimators, extensions of our base model that integrate multiple data sources, and fast scalable inference algorithms. We test our method using simulated data under various dependent population histories and demonstrate the utility of our model in shedding light on evolutionary histories of different variants of SARS-CoV-2.

Revision Rates and Symptom Trends Following Endoscopic Sinus Surgery: Impact of Race on Outcomes.

OBJECTIVE: The purpose of this study is to determine the impact of demographics and sinonasal comorbidities on the revision rate of functional endoscopic sinus surgery (FESS) for chronic rhinosinusitis (CRS). BACKGROUND: Although endoscopic sinus surgery (ESS) is often successful in providing long-term relief for patients suffering from CRS, revision surgery can occur. There is conflicting literature on the impact of race on FESS outcomes. METHODS: A single-center retrospective cohort study of patients that underwent FESS for CRS between January 1, 2015 and June 1, 2021 at a single tertiary care academic center. RESULTS: A total of 682 patients between the ages of 18 and 89 underwent primary ESS between January 1, 2015 and June 1, 2021 and were included in this study. Of these patients, 388 (56.9%) were female, with an average age of 48.6 ± 16.7. Thirty-eight patients (5.6%) underwent revision sinus surgery during the study period. Patients that identified as White had significantly lower rates of revision sinus surgery (4.1%) than non-White patients (10.7%), including those identifying as Asian, Black, multiracial, or other. On multivariate analysis, non-White race (OR 4.933), polyposis (3.175), and high preoperative SNOT-22 scores (OR 1.029) were independently associated with revision sinus surgery. The mean preoperative SNOT-22 for all participants was 39.1 ± 22.0, whereas the mean postoperative SNOT-22 was 20.6 ± 17.5 (p < 0.001). CONCLUSION: Race plays an important role in outcomes following revision sinus surgery that is independent of location and insurance status. More studies are required to assess the reason race plays an important role in outcomes following revision sinus surgery. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 133:2878-2884, 2023.

A case report of uremic tumoral calcinosis in the head and neck and literature review of calcified lesions of the head and neck.

Soft-tissue calcifications in the head and neck are relatively common and are the result of a wide variety of benign and malignant pathologies. They can present a diagnostic challenge given the broad range of underlying etiologies. Uremic tumoral calcinosis (UTC) is a rare complication of end-stage renal disease (ESRD) resulting from metastatic soft tissue calcification. Common sites include periarticular soft tissues of the shoulders, elbows, and hands (Pan and Chen, 2016). UTC can also affect the cervical spine and mimic osteosarcomas (Zhou et al., 2018). We present the case of a 71-year-old female with hypertension, left carotid artery stenosis, mitral valve prolapse, and ESRD secondary to diabetes mellitus type II (DMII) on peritoneal dialysis who was found to have large, heterogeneous, bilateral calcified neck masses. Given her clinical history, laboratory results, and imaging findings, she was diagnosed with UTC. In addition to this case, we provide an overview of tumoral calcinosis (TC) and a differential diagnosis for calcified lesions of the head and neck.

KS10076, a chelator for redox-active metal ions, induces ROS-mediated STAT3 degradation in autophagic cell death and eliminates ALDH1+ stem cells.

Redox-active metal ions are pivotal for rapid metabolism, proliferation, and aggression across cancer types, and this presents metal chelation as an attractive cancer cell-targeting strategy. Here, we identify a metal chelator, KS10076, as a potent anti-cancer drug candidate. A metal-bound KS10076 complex with redox potential for generating hydrogen peroxide and superoxide anions induces intracellular reactive oxygen species (ROS). The elevation of ROS by KS10076 promotes the destabilization of signal transducer and activator of transcription 3, removes aldehyde dehydrogenase isoform 1-positive cancer stem cells, and subsequently induces autophagic cell death. Bioinformatic analysis of KS10076 susceptibility in pan-cancer cells shows that KS10076 potentially targets cancer cells with increased mitochondrial function. Furthermore, patient-derived organoid models demonstrate that KS10076 efficiently represses cancer cells with active KRAS, and fluorouracil resistance, which suggests clinical advantages.

TNIK Inhibition Has Dual Synergistic Effects on Tumor and Associated Immune Cells.

Treatment with checkpoint inhibitors can be extraordinarily effective in a fraction of patients, particularly those whose tumors are pre-infiltrated by T cells. In others, efficacy is considerably lower, which has led to interest in developing strategies for sensitization to immunotherapy. Using various colorectal cancer mouse models, it is shown that the use of Traf2 and Nck-interacting protein kinase inhibitors (TNIKi) unexpectedly increases tumor infiltration by PD-1+ CD8+ T cells, thus contributing to tumor control. This appears to happen by two independent mechanisms, by inducing immunogenic cell death and separately by directly activating CD8. The use of TNIKi achieves complete tumor control in 50% of mice when combined with checkpoint inhibitor targeting PD-1. These findings reveal immunogenic properties of TNIKi and indicate that the proportion of colorectal cancers responding to checkpoint therapy can be increased by combining it with immunogenic kinase inhibitors.

Differentially Expressed Circular RNAs in Degenerative Diseases Related to Low Back Pain: Potential of Circular RNAs as Biomarkers.

Low back pain (LBP) is a major cause of disability worldwide. Nevertheless, given the complex pathophysiology of LBP, its etiological diagnosis remains a challenging process. Thus, identifying appropriate biomarkers and/or therapeutic targets is crucial for LBP research. Recently, circular RNAs (circRNAs) which are both abundant and sphysiologically stable have received a great deal of attention as potential molecular biomarkers. This is part because they can serve as microRNA (miRNA) sponges, inhibit normal miRNA activity. Indeed, it has been reported that circulating and/or tissue-specific circRNAs can be used for diagnosing multiple human diseases, including cancers, neurological diseases, and inflammatory diseases. Since 2015, research on circRNAs involved in LBP-related diseases has been a very active endeavor. Moreover, specific roles for some of the differentially expressed circRNAs have been demonstrated. Thus, the involvement of circRNAs in LBP-related diseases suggests that some of the dysregulated ones may have the potential to serve as therapeutic targets and/or diagnostic biomarkers. This review summarizes the current progress on differentially expressed circRNAs in diseases related to LBP.

Radiologic Analysis of Malar Arch Movement in Reduction Malarplasty Without Bony Resection.

BACKGROUND: Reduction malarplasty has been popular among Asians with a wide facial width. In general, malar setback after bony resection is regarded as the standard objective of reduction malarplasty. However, unnecessary bony resection may lead to various postoperative complications. Therefore, we suggest the use of reduction malarplasty without bony resection to achieve a similar narrowing effect of the facial width, based on radiographic analysis of malar arch movement. PATIENTS AND METHODS: This retrospective study analyzed 48 patients with a wide midface who underwent reduction malarplasty between September 2018 and December 2019. We included 40 cases of advancement repositioning malarplasty (AR) without bony resection and 8 cases of setback reduction malarplasty (SR) with bony resection. The three-dimensional position of the malar arch expressed by coordinates (x, y, and z) on three-dimensional computed tomography scans was used to compare the positional change between the surgical methods. The paired t-test, Wilcoxon text, and independent t-test were used in data analysis, and statistical analysis was performed using SPSS 23.0 software. RESULTS: Medial and superior movement of the freed malar arch segment was significantly different between AR and SR (P < 0.05). Although medialization and superiorization were not significantly different between AR and SR, there was a significant difference in anterior-posterior movement between AR and SR (P < 0.05). CONCLUSION: The radiologic analysis based on malar arch movement between AR and SR showed similar narrowing effects on medialization and superiorization of the malar arch regardless of bony resection. Therefore, the AR can be effectively applied in case of arch dominant type or malar asymmetry. In addition, further comprehensive study including analysis on movement of facial soft tissue following malar bony movement is expected based on this study in near future.

Cadaveric study of deep temporal fascia for autologous rhinoplasty grafts: Dimensions of the temporal compartment in Asians.

BACKGROUND: Due to the anatomical complexity of the deep temporal fascia (DTF), practical guidelines for its safe harvest are lacking. However, since the upper temporal compartment (UTC) contains no vital structures, it may provide safe access for DTF harvest. This study aimed to identify the anatomical structures of the temporal compartment in Asian cadavers and to measure their dimensions to enable safe DTF harvest. METHODS: The anatomical structures surrounding the temporal compartment were identified in 27 hemifaces from 15 Korean cadavers. After dissection, digital images were acquired and craniometric landmarks were placed upon them to identify the boundaries of the temporal compartment. The horizontal and vertical lengths of the temporal compartment were measured and their surface areas were computationally assessed. Subsequently, differences in the results by sex were evaluated. RESULTS: The five-layer anatomical structure of the UTC was clearly visualized. The UTC was bounded by the temporal septa superiorly and inferiorly, the innominate fascia laterally, and the DTF medially. No vital structures were present within the UTC. The vertical and horizontal lengths of the UTC were 6.41±0.67 cm and 10.44±0.83 cm, respectively, and the surface area of the UTC was 48.52±5.65 cm2. No statistically significant differences were observed in any dimensions between male and female patients. CONCLUSIONS: During rhinoplasty, DTF can be harvested as an autologous graft material from the UTC. An anatomical understanding of the UTC will aid in the safe and simple harvest of a sufficient amount of DTF.

Empagliflozin attenuates diabetic tubulopathy by improving mitochondrial fragmentation and autophagy.

We examined the effects of empagliflozin, a selective inhibitor of Na+-glucose cotransporter 2, on mitochondrial quality control and autophagy in renal tubular cells in a diabetic environment in vivo and in vitro. Human renal proximal tubular cells (hRPTCs) were incubated under high-glucose conditions. Diabetes was induced with streptozotocin in male C57BL/6J mice. Improvements in mitochondrial biogenesis and balanced fusion-fission protein expression were noted in hRPTCs after treatment with empagliflozin in high-glucose media. Empagliflozin also increased autophagic activities in renal tubular cells in the high-glucose environment, which was accompanied with mammalian target of rapamycin inhibition. Moreover, reduced mitochondrial reactive oxygen species production and decreased apoptotic and fibrotic protein expression were observed in hRPTCs after treatment with empagliflozin, even in the hyperglycemic circumstance. Importantly, empagliflozin restored AMP-activated protein kinase-α phosphorylation and normalized levels of AMP-to-ATP ratios in hRPTCs subjected to a high-glucose environment, which suggests the way that empagliflozin is involved in mitochondrial quality control. Empagliflozin effectively suppressed Na+-glucose cotransporter 2 expression and ameliorated renal morphological changes in the kidneys of streptozotocin-induced diabetic mice. Electron microscopy analysis showed that mitochondrial fragmentation was decreased and 8-hydroxy-2'-deoxyguanosine content was low in renal tubular cells of empagliflozin treatment groups compared with those of the diabetic control group. We suggest one mechanism related to the renoprotective actions of empagliflozin, which reverse mitochondrial dynamics and autophagy.

Understanding the Anatomy of the Transverse Nasalis Aponeurotic Fibers and Its Importance in Asian Rhinoplasty.

BACKGROUND: A complete release of the transverse nasalis aponeurotic fibers (TNAFs) during Asian rhinoplasty is critical for accurate positioning of the nasal implant and lengthening of the short nose. The objectives of this article are to clarify the anatomy of the TNAFs using cadaveric dissections and to present the clinical results after complete TNAF release in Asian rhinoplasty. METHODS: An anatomical dissection was performed in 8 cadavers to study the TNAFs, specifically the origin, insertion, and boundary of the TNAFs and the effect of the TNAF release on nasal length. Between January 2012 and December 2014, 2314 open implant augmentation rhinoplasties (1777 primary and 537 secondary) were performed by the senior author (J.J.). The records of these patients were retrospectively reviewed for results of TNAF release. A separately designed prospective clinical study was performed to document the nasal envelope extension after TNAF release in 52 consecutive patients. RESULTS: In the cadaver study, the anatomy and the boundaries of the TNAFs were clearly visualized and documented. With accurate release of the TNAFs, the ideal pocket for nasal implant can be defined, and the effect of the release of the TNAFs recorded. Release of the TNAFs also allows extension of the nasal envelope. However, measurements of the nasal envelope were not studied in the cadaver because the skin was degloved.From the clinical study with a follow-up ranging from 6 months to 1.5 years, the overall complication of open rhinoplasty using silicone implants incorporating TNAF release was 6%. In this group, 3.4% of patients required revision rhinoplasty. Releasing the TNAFs ensures an accurate implant pocket reducing the risk of implant deviation and implant visibility and increases the nasal length by 2.1 mm. CONCLUSIONS: Complete release of the TNAFs is especially important in Asian rhinoplasty to facilitate accurate pocket dissection, allowing the extension of the nasal envelope in order to correct short nose or secondary contracted nose.

Eccrine Spiradenoma of the Scalp.

Eccrine spiradenoma is an uncommon benign adnexal tumor originating from the eccrine sweat gland. We diagnosed a eccrine spiradenoma on a 55-year-old man with histopathologic confirmation upon biopsy followed by complete resection, who had visited our clinic with a chief complain of occipital scalp mass. The solitary eccrine spiradenoma occurring in the scalp is rarely to be seen and should be considered as a differential diagnosis for a solitary cystic mass of the scalp.

Reduction of the Isolated Anterior Wall of the Maxillary Sinus Fracture with Double Urinary Balloon Catheters and Fibrin Glue.

BACKGROUND: Conservative treatment is performed for isolated anterior wall of the maxillary sinus fractures, in many cases when the fracture is clinically not severe and asymptomatic. Despite the absence of symptoms, complications such as sinusitis, rhinitis, and chronic purulent secretion may develop; therefore, successful reduction is required. We attempted to reduce the risk of complications using an alternative technique: reduction of the fracture with two urinary balloon catheters inserted through the maxillary ostium and fixation using fibrin glue, which minimizes the damage to the bony fragments and sinus mucosa. METHODS: In this study, 38 patients who were diagnosed with an isolated anterior wall of the maxillary sinus fracture at our hospital between January 2014 and January 2017 were enrolled. The fracture site was exposed via the Caldwell-Luc approach followed by reduction through the insertion of two urinary balloon catheters using a nasal endoscope and fixation with fibrin glue. The sex, cause of fracture, physical examination, and presence of complications were examined and patient's medical records and facial bone computed tomography scans were analyzed. RESULTS: Radiological evaluation showed that there was no evidence of collapsed reduction fragments. Although some patients had remaining symptoms of hypoesthesia (15%; 3 patients), there were no complications such as infection, rhinitis, sinusitis, and chronic purulent secretion at the surgical site. CONCLUSION: In this study, we present an alternative surgical technique using two urinary balloon catheters and fibrin glue for the successful reconstruction of an isolated anterior wall of the maxillary sinus fracture. This technique enables precise restoration with a reduced risk of complications.

Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction.

TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

Sustained overexpression of Redd1 leads to Akt activation involved in cell survival.

Herein, we show that the constitutive overexpression of Redd1, a negative regulator of mTORC1, induces Akt activation in lung cancer cells. Akt phosphorylation was reduced to basal levels by Rictor siRNA, suggesting the involvement of mTORC2 in this process. Perifosine and PP242, selective inhibitors of Akt and mTORC1/2, respectively, efficiently suppressed the Akt phosphorylation that was induced by the sustained overexpression of Redd1 and increased the sensitivity of the cells to cisplatin. Therefore, the sustained overexpression of Redd1 leads to mTORC1 inhibition and to consequent Akt activation that is involved in cell survival. This finding highlights the importance of Akt activation as a therapeutic target to overcome resistance to chemotherapy.

Inhibition of S6K1 enhances glucose deprivation-induced cell death via downregulation of anti-apoptotic proteins in MCF-7 breast cancer cells.

Nutrient-limiting conditions are frequently encountered by tumor cells in poorly vascularized microenvironments. These stress conditions may facilitate the selection of tumor cells with an inherent ability to decrease apoptotic potential. Therefore, selective targeting of tumor cells under glucose deprivation conditions may provide an effective alternative strategy for cancer therapy. In the present study, we investigated the effects of S6 kinase 1 (S6K1) inhibition on glucose deprivation-induced cell death and the underlying mechanisms in MCF-7 breast cancer cells. PF4708671, a selective inhibitor of S6K1, and knockdown of S6K1 with specific siRNA enhanced cell death induced under glucose deprivation conditions. Moreover, inhibition of S6K1 led to apoptosis in glucose-starved MCF-7 cells via downregulation of the anti-apoptotic proteins, Mcl-1 and survivin. Further experiments revealed that sorafenib, shown to be involved in Mcl-1 and survivin downregulation via mTOR/S6K1 inhibition significantly promotes cell death under glucose deprivation conditions. These findings collectively suggest that S6K1 plays an important role in tumor cell survival under stress conditions, and thus inhibition of S6K1 may be an effective strategy for sensitizing cells to glucose deprivation.

Activin A stimulates mouse macrophages to express APRIL via the Smad3 and ERK/CREB pathways.

A proliferation-inducing ligand (APRIL) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we investigated the role and signaling mechanisms of activin A in APRIL expression by mouse macrophages. Activin A markedly enhanced APRIL expression in mouse macrophages at both the transcriptional and protein levels. Overexpression of dominant-negative (DN)-Smad3 and SB431542 abrogated activin-induced APRIL transcription. Furthermore, activin A induced Smad3 phosphorylation. These results indicate that activin A enhances APRIL expression through both activin receptor-like kinase 4 (ALK4) and Smad3. In a subsequent analysis of activin A signaling, it was found that PD98059, an extracellular signal-related kinase (ERK) inhibitor, eliminated activin A-induced APRIL expression. On the other hand, overexpression of cAMP responsive element-binding protein (CREB), a molecule downstream of ERK, augmented activin A-induced APRIL expression, and this effect could be abolished by PD98059. This finding that activin A induces ERK and CREB phosphorylation suggests that ERK and CREB act as intermediates in APRIL expression. Taken together, these results demonstrate that activin A can enhance APRIL expression through two different pathways, Smad3 and ERK/CREB.