Impact of Anti-PEG IgM Induced via the Topical Application of a Cosmetic Product Containing PEG Derivatives on the Antitumor Effects of PEGylated Liposomal Antitumor Drug Formulations in Mice.

Poly(ethylene glycol) (PEG) is used in many common products, such as cosmetics. PEG, however, is also used to covalently conjugate drug molecules, proteins, or nanocarriers, which is termed PEGylation, to serve as a shield against the natural immune system of the human body. Repeated administration of some PEGylated products, however, is known to induce anti-PEG antibodies. In addition, preexisting anti-PEG antibodies are now being detected in healthy individuals who have never received PEGylated therapeutics. Both treatment-induced and preexisting anti-PEG antibodies alter the pharmacokinetic properties, which can result in a subsequent reduction in the therapeutic efficacy of administered PEGylated therapeutics through the so-called accelerated blood clearance (ABC) phenomenon. Moreover, these anti-PEG antibodies are widely reported to be related to severe hypersensitivity reactions following the administration of PEGylated therapeutics, including COVID-19 vaccines. We recently reported that the topical application of a cosmetic product containing PEG derivatives induced anti-PEG immunoglobulin M (IgM) in a mouse model. Our finding indicates that the PEG derivatives in cosmetic products could be a major cause of the preexistence of anti-PEG antibodies in healthy individuals. In this study, therefore, the pharmacokinetics and therapeutic effects of Doxil (doxorubicin hydrochloride-loaded PEGylated liposomes) and oxaliplatin-loaded PEGylated liposomes (Liposomal l-OHP) were studied in mice. The anti-PEG IgM antibodies induced by the topical application of cosmetic products obviously accelerated the blood clearance of both PEGylated liposomal formulations. Moreover, in C26 tumor-bearing mice, the tumor growth suppressive effects of both Doxil and Liposomal l-OHP were significantly attenuated in the presence of anti-PEG IgM antibodies induced by the topical application of cosmetic products. These results confirm that the topical application of a cosmetic product containing PEG derivatives could produce preexisting anti-PEG antibodies that then affect the therapeutic efficacy of subsequent doses of PEGylated therapeutics.

Association of local steroid injection as a risk factor for electrocoagulation syndrome after esophageal endoscopic submucosal dissection.

BACKGROUND: Postendoscopic submucosal dissection electrocoagulation syndrome (PEECS) is commonly observed after performing endoscopic submucosal dissection (ESD) for esophageal neoplasia. However, data on the incidence and risk factors for PEECS in the esophagus are lacking due to an unclear definition of PEECS and varied clinical settings. Therefore, we aimed to determine the risk factors for PEECS in patients undergoing ESD for esophageal neoplasia. METHODS: We retrospectively reviewed data of relevant clinical and endoscopy-specific parameters from 202 consecutive patients with esophageal neoplasias (139 carcinomas and 63 dysplasias) who underwent ESD under general anesthesia. Esophageal PEECS was defined by satisfying at least two of the following criteria: fever ≥ 37.8 °C, leukocytosis ≥ 10,800/mm3, and localized chest pain ≥ 5/10 points as assessed on a numeric rating scale within 24 h after ESD. Significant factors associated with PEECS were determined by regression analysis. RESULTS: PEECS was recorded in 98 of 202 (48.5%) patients. Patients with PEECS exhibited a larger tumor size (25.0 vs. 17.0 mm, P = 0.002), longer procedure (40.0 vs. 29.5 min, P = 0.021) and hemostasis times (5.0 vs. 3.5 min, P = 0.004), required greater submucosal injection volume (60.0 mL vs. 50.0 mL, P = 0.030), and had a lower rate of local steroid injection (4.1% vs. 12.5%, P = 0.029) than those without PEECS. Multivariate regression analysis revealed tumor size ≥ 17 mm (P = 0.047), procedure time ≥ 33 min (P = 0.027), and hemostasis time ≥ 5 min (P = 0.007) as risk factors for PEECS. In addition, local steroid injection was a significant negatively associated factor (P = 0.001). CONCLUSIONS: Patients with a large tumor, prolonged procedure and hemostasis times are at a high risk of PEECS occurrence. Further, local steroid injection is a negatively associated factor.

Individual characteristics and environmental factors influencing preschoolers' emotional eating.

Emotional eating, which refers to eating in response to emotional states, is prevalent in early childhood. Executive function (EF) and sleep problems are related to preschoolers' self-regulatory abilities during the day and night and have been reported to be associated with their emotional eating. These associations can be stronger in emotionally stressful situations, such as controlling feeding practices. This study explored the role of preschoolers' EF and sleep problems as child characteristics, as well as maternal feeding practices as environmental factors influencing emotional eating during the preschool period. Participants included 363 Korean mothers with preschoolers aged 3- to 5-years old (190 boys, 173 girls). Mothers reported on their own feeding practices, and preschoolers' EF, sleep problems, and emotional eating. Results indicated that preschoolers' EF was negatively associated with emotional over- and undereating, and this association was stronger when mothers applied more pressure to eat. Maternal monitoring had a similar effect, with emotional overeating exerting a greater impact with low levels of maternal monitoring. Finally, maternal pressure to eat moderated the influence of preschoolers' sleep problems on emotional overeating, with higher pressure to eat predicting a stronger relationship between sleep problems and emotional overeating. These findings suggest that maternal feeding practices, which are relatively modifiable, should be considered an important element in intervention programs aimed at preventing emotional eating in preschool children.

Factors associated with age-related changes in oral diadochokinesis and masticatory function in healthy old adults.

BACKGROUND: This cross-sectional study aimed to identify factors associated with age-related changes in masticatory performance (MP) and oral diadochokinesis (ODK) and to provide normal values in healthy old adults for the diagnosis of oral frailty. METHODS: A total of 385 participants were divided into three age groups (Gr1-3): 20-64 years, 65-74 years, and ≥ 75 years. To investigate tongue-lip motor function, ODK was assessed as the number of repetitions of the monosyllables /pa/ta/ka/. Four questionnaires were used to assess subjective masticatory ability, cognitive ability, and psychological status. MP, bite force, and occlusal area were tested to assess dynamic objective masticatory function, and the number of remaining teeth and functional tooth pairs were determined to assess static objective masticatory function. Handgrip strength (HG), oral dryness, and tongue pressure (TP) were assessed to identify influencing factors. Intergroup differences were evaluated by ANOVA and the Kruskal‒Wallis test, and correlations between ODK and orofacial factors were evaluated. RESULTS: This study revealed significant age-related declines in TP, HG, and ODK, especially after 65 years of age. Factors affecting MP were posterior teeth, the Eichner index, bite force, occluding area, the Korean Mini-Mental State Examination (KMMSE) score, and ODK. Each ODK syllable was associated with different factors, but common factors associated with ODK were MP, HG, and PHQ-9 score. For the syllables /pa/ta/, the Eichner Index, TP, and oral dryness were also associated. For the syllable /ka/ in Gr3, MP, TP, HG, oral dryness, and the KMMSE score were associated. CONCLUSIONS: These results could provide practical guidelines for oral rehabilitation in old adults and contribute to improving the understanding of age-related changes in oral function and the multidimensional nature of masticatory dynamics.

Synergistic Therapy for Graves' Ophthalmopathy-Associated Eyelid Retraction: Steroid, 5-FU, and Botulinum Neurotoxin a Combination.

Background: Graves' ophthalmopathy (GO) is characterized by upper eyelid retraction (UER), the most prevalent clinical sign. We aimed to assess the clinical efficacy of a multimodal combination of steroids, 5-fluorouracil (5-FU), and botulinum neurotoxin A (BoNT-A) injections in managing UER with GO and analyze the clinical factors in relation to the injection response. Methods: A total of 37 eyes from 23 patients were enrolled for UER with GO. At the endocrinology clinic, the patients were referred to the ophthalmology clinic after taking antithyroid medication for an average of 5.76 months (13 patients), while 10 patients were initially diagnosed with GO and referred to the endocrinology clinic for management of the thyroid hormone function. They performed an orbital computed tomography (CT) scan and measured the cross-sectional area of the orbit, orbital fat, and each extra ocular muscle (EOM) except for the inferior oblique muscle 4 mm behind the eyeball. Each of the EOMs and orbital fat were calculated as a ratio to the total orbit area. A total of 0.1 cc of triamcinolone (40 mg/mL), dexamethasone (5 mg/mL), 5-FU, and BoNT-A (2.5 units) was injected transconjunctivally. Medical records were examined and photographs were utilized to assess MRD1, inferior palpebral fissure (IPF), and lid lag during down gaze before and after the injection. The patients were divided into two groups: responders (more than 1 mm decrease in MRD1 after injection) and non-responders. During the follow-up period (11.0 ± 11.6 months), any potential adverse effects were monitored. Results: CAS decreased from 3.0 ± 0.8 to 1.4 ± 0.5 after the injection, and MRD1 decreased from 5.0 ± 0.9 mm to 4.5 ± 1.3 mm. Sixty percent of the patients were responders. Before and after the injection, the difference between IPF and MRD1 in responders was 0.60 ± 1.10 mm and 0.90 ± 0.90 mm, respectively, whereas, in non-responders, it was -0.57 ± 0.88 mm and -0.15 ± 0.75 mm, respectively. In the responders, pre-injection IPF and FT4 were significantly higher (p < 0.05). Responders had a larger EOM cross-sectional area (153.5 ± 18.0 mm2), including a larger lateral rectus muscle cross-sectional area (37.6 ± 9.7 mm2) than non-responders (132.0 ± 27.9 mm2; 29.1 ± 8.1 mm2). In responders, the treatment effect on IPF and MRD1 remained consistent at 1.2 ± 3.4 mm and 1.2 ± 1.6 mm, respectively, during the latest follow-up assessment. Conclusions: The combination injection of corticosteroids, 5-FU, and BoNT-A would be effective, especially, in patients with hyperthyroidism and an elongated IPF. Additionally, an increase in EOM cross-sectional area on CT, up to 150 mm2, may serve as an additional positive indicator for the use of multimodal injections in UER with GO.

Sex differences in inflammation correlated with estrogen and estrogen receptor-ß levels in azoxymethane/dextran sodium sulfate-induced colitis-associated colorectal cancer mice.

Colorectal cancer (CRC) is a type of cancer that develops in the colon or rectum and is the second leading cause of cancer-related death worldwide. Several epidemiology studies have identified a significant sexual dimorphism in CRC, with women exhibiting a lower incidence rate and delayed onset compared to men. This study aims to investigate the sexual dimorphism in the inflammatory response in colitis-associated CRC and its relationship with estrogen and estrogen receptors. An azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model was used to induce colitis-associated CRC. Five-week-old male and female mice were randomly assigned into either the control group or the AOM/DSS CRC group, with 10 mice in each group. Colitis-associated CRC was induced by injecting AOM (10 mg/kg) and administering two-cycles of DSS treatment in the drinking water. The results revealed a significant decrease in colon length exclusively in the female group, indicating more severe colonic inflammation (P < 0.01). A significant interaction was identified between sex and AOM/DSS treatment in the female AOM/DSS group, with higher visceral fat weight compared to their male counterparts (P < 0.05). The female AOM/DSS group also exhibited elevated production of M1 macrophage-related pro-inflammatory cytokines, suggesting increased tumor-associated macrophage activity. Surprisingly, the male AOM/DSS group showed a marked increase in serum estradiol levels, while the female AOM/DSS group exhibited a decrease compared to the normal control group. Additionally, a notable upregulation of both estrogen receptor α and estrogen receptor ß expression was observed in the colon tissues of the AOM/DSS groups compared to the normal control groups, with estrogen receptor ß expression being particularly pronounced in females. Taken together, our findings suggest that a decline in endogenous estrogen and increased estrogen receptors potentially contribute to the pro-inflammatory response in early CRC by augmenting cytokine expressions associated with M1 macrophage polarization in females.

Long-term nivolumab treatment possibly associated with aseptic meningitis.

Nivolumab is a programmed death-1 receptor blocker within the family of medications called immune checkpoint inhibitors (ICIs). Although generally well tolerated, cases of immune-related adverse events (irAEs) have been reported. We present a case of a man being treated with nivolumab for renal cell carcinoma who presented to the emergency department with problems of headache, fever and disorientation. After extensive evaluation, a diagnosis of immunotherapy-induced aseptic meningitis was considered more probable than infectious. Due to stable clinical status, no treatment was initiated, and the patient's condition improved spontaneously. The patient was discharged home. To date, only a handful of prior cases of nivolumab-induced meningitis have been reported. Our case demonstrates that irAEs can occur years after the initiation of ICIs. This was a milder presentation of a neurological irAE that resolved spontaneously with watchful waiting, showing that irAEs are likely an evolving spectrum of disease for which clinicians should be aware.

Analysis of volatile compounds, betaine, and antioxidant effect in goji berry (Lycium barbarum L.) powder extracted by various drying methods and extraction solvents.

Goji berry (Lycium barbarum L.), a deciduous solanaceous shrub, were subjected to extraction using five solvents (water, 50% and 70% ethanol, and 50% and 70% methanol) and dried using two methods: freeze drying (FD) and spray drying (SD). To investigate the chemical properties of these various goji berry powders, an examination was conducted on the content of volatile compounds, betaine, antioxidant effect, total phenolic content (TPC), and total flavonoid compounds (TFC) (p < 0.05). The total volatile compound content was highest in SD powder with 50% ethanol extract, showing a 66.7% increase over the control. The betaine content was in the range of 9.25-31.9 mg/g dry weight, and it exhibited a significant increase with higher water concentration in the extraction solvent. Betaine, total phenolic compounds and total flavonoid compounds showed a significant increase in the sequence of SD followed by FD (p < 0.05). Overall, the SD sample showed superior benefits when evaluating volatile compounds, betaine, and antioxidant effect. SD was more suitable for drying goji berry, as it retains its appearance and biological activity.

A combination of myokines and genistein suppresses cancer stemness in MCF-7 human breast cancer cells.

BACKGROUND/OBJECTIVES: Breast cancer is considered a serious health issue worldwide and is influenced by risk factors, including physical inactivity and unhealthy diet. Myokines secreted by muscles during physical activity play a crucial role in cancer development and the immune system. Genistein (Gen), an isoflavone primarily in legumes, induces anti-cancer activity by regulating cancer stem cells (CSCs). Therefore, this study investigated the potential anti-cancer effect of a combination of myokine and Gen on the human breast cancer MCF-7 cells. MATERIALS/METHODS: MCF-7, a human breast cancer cell line, was used for in vitro study. The cell viability of MCF-7 cells was evaluated in response to treatment with myokines, irisin (Iri), oncostatin M (OSM), and Gen using the MTT assay. Clonogenic and sphere formation assays were used to evaluate the self-renewal capacity of breast CSCs. The mRNA expression levels of stem cell markers were analyzed in MCF-7 breast cancer cells. RESULTS: Administering Iri or OSM with Gen significantly inhibited the self-renewal capacity of MCF-7 cells. In addition, mRNA expression of breast CSC markers SOX2 and OCT4, which are characteristic of CSCs, was suppressed by both myokine and Gen. However, combining Iri or OSM with Gen was the most effective treatment. CONCLUSION: These results suggested that combining Iri or OSM with Gen has an additive effect on breast CSCs by regulating self-renewal capacity and expression of CSCs markers. Therefore, the combination of myokines and Gen may have the therapeutic potential for treating breast cancer and improving the quality of life of cancer patients.

Combination of oxaliplatin and ß-carotene suppresses colorectal cancer by regulating cell cycle, apoptosis, and cancer stemness in vitro.

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide with a high recurrence rate. Oxaliplatin (OXA) resistance is one of the major reasons hindering CRC therapy. ß-Carotene (BC) is a provitamin A and is known to have antioxidant and anticancer effects. However, the combined effect of OXA and BC has not been investigated. Therefore, this study investigated the anticancer effects and mechanism of the combination of OXA and BC on CRC. MATERIALS/METHODS: In the present study, the effects of the combination of OXA and BC on cell viability, cell cycle arrest, and cancer stemness were investigated using HCT116, HT29, OXA-resistant cells, and human CRC organoids. RESULTS: The combination of OXA and BC enhanced apoptosis, G2/M phase cell cycle arrest, and inhibited cancer cell survival in human CRC resistant cells and CRC organoids without toxicity in normal organoids. Cancer stem cell marker expression and self-replicating capacity were suppressed by combined treatment with OXA and BC. Moreover, this combined treatment upregulated apoptosis and the stem cell-related JAK/STAT signaling pathway. CONCLUSIONS: Our results suggest a novel potential role of BC in reducing resistance to OXA, thereby enhances the anticancer effects of OXA. This enhancement is achieved through the regulation of cell cycle, apoptosis, and stemness in CRC.

Diffuse-Type Tenosynovial Giant Cell Tumor: What Are the Important Findings on the Initial and Follow-Up MRI?

Tenosynovial giant cell tumor (TSGCT) is a rare soft tissue tumor that involves the synovial lining of joints, bursae, and tendon sheaths, primarily affecting young patients (usually in the fourth decade of life). The tumor comprises two subtypes: the localized type (L-TSGCT) and the diffuse type (D-TSGCT). Although these subtypes share histological and genetic similarities, they present a different prognosis. D-TSGCT tends to exhibit local aggressiveness and a higher recurrence rate compared to L-TSGCT. Magnetic resonance imaging (MRI) is the preferred diagnostic tool for both the initial diagnosis and for treatment planning. When interpreting the initial MRI of a suspected TSGCT, it is essential to consider: (i) the characteristic findings of TSGCT-evident as low to intermediate signal intensity on both T1- and T2-weighted images, with a blooming artifact on gradient-echo sequences due to hemosiderin deposition; (ii) the possibility of D-TSGCT-extensive involvement of the synovial membrane with infiltrative margin; and (iii) the resectability and extent-if resectable, synovectomy is performed; if not, a novel systemic therapy involving colony-stimulating factor 1 receptor inhibitors is administered. In the interpretation of follow-up MRIs of D-TSGCTs after treatment, it is crucial to consider both tumor recurrence and potential complications such as osteoarthritis after surgery as well as the treatment response after systemic treatment. Given its prevalence in young adult patents and significant impact on patients' quality of life, clinical trials exploring new agents targeting D-TSGCT are currently underway. Consequently, understanding the characteristic MRI findings of D-TSGCT before and after treatment is imperative.

A study on the consumer behavior and attitude toward low-sodium convenience store foods.

BACKGROUND/OBJECTIVES: This study aims to explore the potential of convenience stores as platforms for healthy food consumption, including low-sodium options, in response to the increasing trend of meal behaviors at convenience stores and the growing demand for healthy eating. SUBJECTS/METHODS: In the study, 627 Korean participants aged 10 to 39 were involved. A self-reported questionnaire survey was used and questions were regarding purchase patterns, consumption behaviors, perceptions and selection attributes of convenience store foods, and consumer perception factors for low-sodium options. Data analysis was conducted using SPSS 26.0 (SPSS, Version 26.0 for Windows, SPSS Inc., Chicago, IL, USA). RESULTS: The study uncovered significant disparities in the consumption behavior and perception of convenience store foods, as well as variations in the importance and satisfaction levels with convenience store food attributes, including consumer perception factors for low-sodium options, based on sex and age. Furthermore, it was observed that awareness of the need for low-sodium options significantly influenced purchase intentions. CONCLUSION: This study analyzed consumer attitude toward low-sodium convenience store foods to assess the potentiality for promoting healthy eating in convenience stores. These findings indicate the important role that convenience stores can play as platforms for healthy food sales.

Exercise affects high-fat diet-stimulated breast cancer metastasis through irisin secretion by altering cancer stem cell properties.

Background: Regular physical activities reduce the growth of breast cancer, but research on the effects of steady exercise on metastasis and its mechanisms is limited. In this study, the effects of steady exercise on breast cancer metastasis and its possible mechanism were demonstrated. Methods: Experimental metastasis was induced after 8 weeks of steady exercise using a mouse model. Furthermore, one of the myokines, irisin, was studied to elucidate the effects of metastasis-regulating protein expression, and colony and sphere formation, which are cancer stem cell properties. Results: Low- and moderate-intensity exercise significantly reduced the number and volume of metastasized tumors. Among myokines, only irisin was significantly increased by steady exercise but decreased by a high-fat diet. In vitro studies, irisin significantly decreased the number of colonies and sphere formation. Irisin also inhibited cell migration and invasion and suppressed the malignancy of breast cancer cells by reducing the expression of vimentin, MMP-2, MMP-9, and HIF-1 and by increasing the expression of TIMP-1 and TIMP-2. Conclusion: Steady exercise modulates myokine secretions and among them, irisin suppresses breast cancer metastasis by decreasing self-renewal properties and invasion regulating protein expressions. Thus, regular exercise may be beneficial in the prevention of breast tumor metastasis.

3D Printing of Materials and Printing Parameters with Animal Resources: A Review.

3D printing technology enables the production of creative and personalized food products that meet consumer needs, such as an attractive visual appearance, fortification of specific nutrients, and modified textures. To popularize and diversify 3D-printed foods, an evaluation of the printing feasibility of various food pastes, including materials that cannot be printed natively, is necessary. Most animal resources, such as meat, milk, and eggs, are not inherently printable; therefore, the rheological properties governing printability should be improved through pre-/post-processing or adding appropriate additives. This review provides the latest progress in extrusion-based 3D printing of animal resource-based inks. In addition, this review discusses the effects of ink composition, printing conditions, and post-processing on the printing performance and characteristics of printed constructs. Further research is required to enhance the sensory quality and nutritional and textural properties of animal resource-based printed foods.

Sweet-bitter taste interactions in binary mixtures of sweeteners: Relationship between taste receptor activities and sensory perception.

This study investigated the effects of various binary sweetener mixtures on sweetness enhancement and their interactions with sweet or bitter taste receptors, focusing on sensory perception and receptor activity. Acesulfame K or saccharin was mixed with allulose, aspartame, erythritol, fructose, glucose, or sucrose to match a target sucrose sweetness. The effects of the mixtures on sweet and bitter taste receptors (in the human embryonic kidney -293 cells) and sensory taste intensities were evaluated. Sweetness enhancement at the sweet taste receptor level was observed in some cases, with several monosaccharides reducing the acesulfame K- or saccharin-induced bitter taste receptor activity. Combining acesulfame K or saccharin with any of the six sweeteners perceptually enhanced sweetness (60% âˆ¼ 100% in 50:50 ratio), correlating with a reduction in inherent bitterness (-35% âˆ¼ -63% in 50:50 ratio). This finding suggests that sweetness perception likely increased because the monosaccharides mitigate the activation of bitter receptors caused by high-potency sweeteners.

Umami taste receptor suppresses cancer cachexia by regulating skeletal muscle atrophy in vivo and in vitro.

BACKGROUND/OBJECTIVES: The umami taste receptor (TAS1R1/TAS1R3) is endogenously expressed in skeletal muscle and is involved in myogenesis; however, there is a lack of evidence about whether the expression of the umami taste receptor is involved in muscular diseases. This study aimed to elucidate the effects of the umami taste receptor and its mechanism on muscle wasting in cancer cachexia using in vivo and in vitro models. MATERIALS/METHODS: The Lewis lung carcinoma-induced cancer cachexia model was used in vivo and in vitro, and the expressions of umami taste receptor and muscle atrophy-related markers, muscle atrophy F-box protein, and muscle RING-finger protein-1 were analyzed. RESULTS: Results showed that TAS1R1 was significantly downregulated in vivo and in vitro under the muscle wasting condition. Moreover, overexpression of TAS1R1 in vitro in the human primary cell model protected the cells from muscle atrophy, and knockdown of TAS1R1 using siRNA exacerbated muscle atrophy. CONCLUSION: Taken together, the umami taste receptor exerts protective effects on muscle-wasting conditions by restoring dysregulated muscle atrophy in cancer cachexia. In conclusion, this result provided evidence that the umami taste receptor exerts a therapeutic anti-cancer cachexia effect by restoring muscle atrophy.

Effect of Sugar-Free Jelly on Glycemic Metabolism and Its Potential Health Benefits in Non-Diabetic Adults.

Excessive sugar consumption provides energy but has little nutritional value, contributing to the prevalence of obesity. Hence, "sugar-free" products using artificial or natural sweeteners, including sugar alcohols, have become popular. Accordingly, safety concerns and curiosity have arisen. Therefore, this study used a double-blind, crossover design to compare the effects of commercial sugar-free and sugar jellies (control) on the glycemic response in 16 adults without diabetes. Blood samples were collected to measure blood glucose, insulin, glucagon, ghrelin, C-peptide, glycated hemoglobin, and glycated albumin levels, and an oral glucose tolerance test was performed. Questionnaires on satiety and intestinal health were also administered. Sugar-free jellies resulted in significantly lower glucose and insulin levels and a reduced area under the curve while showing higher glucagon levels than the controls. Moreover, the sugar-free jelly initially resulted in the greater secretion of ghrelin; however, after 2 h, the control jelly resulted in higher ghrelin. No significant differences were observed in gut quotient, C-peptide, glycated hemoglobin, and glycated albumin levels. In conclusion, substituting sugar jelly with sugar-free jelly may induce lower blood glucose and insulin levels and higher glucagon levels, indicating a better ability to control glucose metabolism. Appetite was not stimulated by sugar-free jelly consumption.

Benidipine impairs innate immunity converting sublethal to lethal infections in a murine model of spotted fever rickettsiosis.

Spotted fever group rickettsiae are tick-borne obligate intracellular bacteria that infect microvascular endothelial cells. Humans and mammalian infection results in endothelial cell barrier dysfunction and increased vascular permeability. We previously demonstrated that treatment of Rickettsia parkeri-infected cells with the calcium channel blocker benidipine significantly delayed vascular barrier permeability. Thus, we hypothesized that benidipine, known to be safe and effective for other clinical processes, could reduce rickettsia-induced vascular permeability in vivo in an animal model of spotted fever rickettsiosis. Based on liver, lung and brain vascular FITC-dextran extravasation studies, benidipine did not reliably impact vascular permeability. However, it precipitated a deleterious effect on responses to control sublethal R. parkeri infection. Animals treated with benidipine alone had no clinical signs or changes in histopathology and splenic immune cell distributions. Benidipine-treated infected animals had marked increases in tissue and blood bacterial loads, more extensive inflammatory histopathologic injury, and changes in splenic architecture and immune cell distributions potentially reflecting diminished Ca2+ signaling, reduced innate immune cell activation, and loss of rickettsial propagation control. Impaired T cell activation by R. parkeri antigen in the presence of benidipine was confirmed in vitro with the use of NKT cell hybridomas. The unexpected findings stand in stark contrast to recent discussions of the benefits of calcium channel blockers for viral infections and chronic infectious or inflammatory diseases. A role for calcium channel blockers in exacerbation of human rickettsiosis and acute inflammatory infections should be evaluated by a retrospective review of patient's outcomes and medications.

Clinical and radiological features of malformed mesiodens in the nasopalatine canal: an observational study.

OBJECTIVES: The purpose of this study is to investigate the morphological changes that occur when mesiodens is located within the nasopalatine canal, as well as clinical characteristics. METHODS: Clinical records and CT images of patients who had mesiodens in the nasopalatine canal were retrospectively analysed. In addition to demographic information, clinical symptoms and complications associated with extraction of mesiodens were recorded. Using CT images, number, location, size, and tooth morphology were evaluated. RESULTS: This study included 32 patients and 38 mesiodens within the nasopalatine canal. Supernumerary teeth exhibited a characteristic feature of thin and elongated shape in the canal (narrow width and elongation were observed in 96.6% and 53.3% of the patients, respectively). Fusion was found in 4 patients and dilaceration in 12. A complication occurred in 2 patients, which was tooth remnant, not a neurologic complication. Only 5 mesiodens could be detected in the nasopalatine canal on panoramic images. CONCLUSIONS: Morphological abnormalities in mesiodens within the nasopalatine canal were frequently detected, and these could be effectively diagnosed through 3D imaging analysis.

A combination of rebaudioside A and neohesperidin dihydrochalcone suppressed weight gain by regulating visceral fat and hepatic lipid metabolism in ob/ob mice.

Rebaudioside A (Reb A) and neohesperidin dihydrochalcone (NHDC) are known as intense sweeteners. This study aimed to examine the anti-obesity effects of Reb A and NHDC. C57BL/6 J-ob/ob mice were supplemented with Reb A (50 mg/kg body weight [b.w.]), NHDC (100 mg/kg b.w.), or their combination (COMB) for 4 weeks. COMB-supplemented mice showed significant reduction in b.w. gain, food efficiency ratio, and fat mass. Additionally, mice in the COMB group showed suppressed levels of genes related to adipogenesis, lipogenesis, and lipolysis in the perirenal fat and the levels of hepatic triglyceride, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase. The lipogenesis and pro-inflammatory gene expressions were also downregulated in the liver, whereas ß-oxidation related genes were upregulated in the COMB group. In addition, mice that received COMB showed distinct gut microbiota structure, enriched in Blautia and Parabacteroides, and depleted in Faecalibaculum and Mucispirillum, in relation to the control group. These results suggest that supplementation with Reb A and NHDC may be an effective treatment for obesity-related metabolic disorders. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01391-1.