Enterovirus D68 (EV-D68) is one of hundreds of non-polio enteroviruses that typically cause cold-like respiratory illness. The first EV-D68 outbreak in the United States in 2014 aroused widespread concern among the public and health authorities. The infection was found to be associated with increased surveillance of acute flaccid myelitis, a neurological condition that causes limb paralysis in conjunction with spinal cord inflammation. In vitro studies utilising two-dimensional (2D) and three-dimensional (3D) culture systems have been employed to elucidate the pathogenic mechanism of EV-D68. Various animal models have also been developed to investigate viral tropism and distribution, pathogenesis, and immune responses during EV-D68 infection. EV-D68 infections have primarily been investigated in respiratory, intestinal and neural cell lines/tissues, as well as in small-size immunocompetent rodent models that were limited to a young age. Some studies have implemented strategies to overcome the barriers by using immunodeficient mice or virus adaptation. Although the existing models may not fully recapitulate both respiratory and neurological disease observed in human EV-D68 infection, they have been valuable for studying pathogenesis and evaluating potential vaccine or therapeutic candidates. In this review, we summarise the methodologies and findings from each experimental model and discuss their applications and limitations.

UNASSIGNED: Acne vulgaris (AV) is a common problem with a relatively high incidence rate among Asian people. The potential antimicrobial and anti-inflammatory properties of banana peels have been demonstrated in previous studies but have not been studied in cases of AV. Therefore, this study was aimed at investigating the protective effects of banana (Musa balbisiana) peel extract (MBPE) against AV.
UNASSIGNED: Thirty rats were divided into five groups (n = 6 rats per group): an AV group, AV group treated with 0.15% MBPE, AV group administered 0.30% MBPE, AV group administered 0.60% MBPE, and AV group administered clindamycin (the standard drug treatment). We assessed nodule size, bacterial count, histopathology, and cytokine levels (IL-1α, IFN-γ, tumor necrosis factor (TNF)-α, and IL-8). Enzyme linked immunoassays were used to measure the cytokine levels. In addition, we performed molecular docking studies to determine the interactions between phytochemicals (trigonelline, vanillin, ferulic acid, isovanillic acid, rutin, and salsolinol) via the Toll-like receptor 2 (TLR2) and nuclear factor-kappa B (NF-κB) pathways.
UNASSIGNED: All MBPE treatment groups, compared with the AV group, showed suppression of both bacterial growth and proinflammatory cytokine production, as well as resolved tissue inflammation. The nodule size was significantly suppressed in the groups receiving the two highest doses of MBPE, compared with the AV group. However, the pharmacological action of MBPE remained inferior to that of clindamycin. Docking studies demonstrated that rutin was the phytocompound with the most negative interaction energy with TLR2 or NF-κB.
UNASSIGNED: Our results indicated that MBPE has anti-inflammatory effects against AV, by suppressing nodule formation, inhibiting bacterial growth, and decreasing proinflammatory cytokine production.
UNASSIGNED: حب الشباب الشائع مشكلة شائعة، مع معدل حدوث مرتفع نسبيا بين الآسيويين. بالمناسبة، تم إثبات الخصائص المحتملة المضادة للميكروبات والمضادة للالتهابات لقشور الموز في دراسات سابقة؛ ومع ذلك، لم يتم دراستها في حالة حب الشباب. هدفت الدراسة الحالية إلى معرفة التأثيرات الوقائية لمستخلص قشر الموز (موسى بالبسيانا) بسبب حب الشباب.
UNASSIGNED: تم تقسيم ثلاثين جرذا إلى خمس مجموعات (عدد = 6 فئران في كل مجموعة): مجموعة حب الشباب، مجموعة حب الشباب الشائع المعالجة بـ 0.15 ٪ قشر الموز (موسى بالبيسيانا) ، مجموعة حب الشباب الشائع المعالجة بنسبة 0.30 ٪ قشر الموز (موسى بالبيسيانا)، مجموعة حب الشباب الشائع المعالجة 0.60 ٪ قشر الموز (موسى بالبيسيانا)، وحب الشباب الشائع المجموعة التي تم إعطاؤها الكليندامايسين كدواء قياسي. قمنا بتقييم حجم العقيدات وعدد البكتيريا وعلم الأنسجة ومستويات السيتوكين (انترليوكن-1، وانتر فيرون جاما، وعامل نخر العظم-ألفا، انترليوكن-8). تم استخدام المقايسات المناعية المرتبطة بالإنزيم لقياس مستويات السيتوكين. بالإضافة إلى ذلك، أجرينا دراسات الالتحام الجزيئي لتحديد التفاعلات بين المواد الكيميائية النباتية (تريغونيلين، الفانيلين، حمض الفيروليك، حمض الأيزوفانيليك، الروتين، والسالسولينول) عبر مسارات المستقبل الشبيه بالتول-2 والعامل النووي – كابا ب.
UNASSIGNED: أدت جميع جرعات قشر الموز (موسى بالبيسيانا) إلى تثبيط نمو البكتيريا وإنتاج السيتوكينات المنشطة للالتهابات مقارنة بمجموعة حب الشباب، بالإضافة إلى علاج التهاب الأنسجة. تم قمع حجم العقدة بشكل معنوي بأعلى جرعتين من قشر الموز (موسى بالبيسيانا) مقارنة بمجموعة حب الشباب. ومع ذلك، يظل تأثيره الدوائي أدنى من تأثير الكليندامايسين. أظهرت دراسات الالتحام أن المركب النباتي ذو الطاقة التفاعلية الأكثر سلبية مع المستقبل الشبيه بالتول-2 والعامل النووي – كابا ب كان روتيني.
UNASSIGNED: تشير هذه النتائج إلى أن مستخلص قشر الموز (موسى بالبيسيانا) يعمل كعامل مضاد للالتهابات ضد حب الشباب الشائع، عن طريق قمع تكوينات العقيدات، وتثبيط نمو البكتيريا، وتقليل إنتاج السيتوكينات المسببة للالتهابات.

Liver fibrosis is a common result of liver injury owing to various kinds of chronic liver diseases. A deeper understanding of the pathophysiology of liver fibrosis and identifying potential therapeutic targets of liver fibrosis is important because liver fibrosis may progress to advanced liver diseases, such as cirrhosis and hepatocellular carcinoma. Despite numerous studies, the underlying mechanisms of liver fibrosis remain unclear. Mechanisms of the development and progression of liver fibrosis differ according to etiologies. Therefore, appropriate liver fibrosis models should be selected according to the purpose of the study and the type of underlying disease. Many in vivo animal and in vitro models have been developed to study liver fibrosis. However, there are no perfect preclinical models for liver fibrosis. In this review, we summarize the current in vivo and in vitro models for studying liver fibrosis and highlight emerging in vitro models, including organoids and liver-on-a-chip models. In addition, we discuss the mechanisms and limitations of each model.

UNASSIGNED: The onset of insulin resistant diabetes has been associated with a high-sucrose diet in vertebrates and invertebrates. However, various parts of Spondias mombin reportedly possess antidiabetic potential. However, the antidiabetic efficacy of S. mombin stem bark in high-sucrose diet-induced Drosophila melanogaster model has not been explored. In this study, the antidiabetic and antioxidant effects of the solvent fractions of S. mombin stem bark were evaluated using in vitro, in vivo, and in silico methods.
UNASSIGNED: Successive fractionation of S. mombin stem bark ethanol extract was performed; the resulting fractions were subjected to in vitro antioxidant and antidiabetic assays using standard protocols. The active compounds identified from the high-performance liquid chromatography (HPLC) study of the n-butanol fraction were docked against the active site of Drosophila α-amylase using AutoDoc Vina. The n-butanol and ethyl acetate fractions of the plant were incorporated into the diet of diabetic and nondiabetic flies to study the in vivo antidiabetic and antioxidant properties.
UNASSIGNED: The results obtained revealed that n-butanol and ethyl acetate fractions had the highest in vitro anti-oxidant capacity by inhibiting 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power, and hydroxyl radical followed by significant inhibition of α-amylase. HPLC analysis revealed the identification of eight compounds with quercetin having the highest peak followed by rutin, rhamnetin, chlorogenic acid, zeinoxanthin, lutin, isoquercetin, and rutinose showing the lowest peak. The fractions restored the glucose and antioxidant imbalance in diabetic flies, which is comparable with the standard drug (metformin). The fractions were also able to upregulate the mRNA expression of insulin-like peptide 2, insulin receptor, and ecdysone-inducible gene 2 in diabetic flies. The in silico studies revealed the inhibitory potential of active compounds against α-amylase with isoquercetin, rhamnetin, rutin, quercetin, and chlorogenic acid having higher binding affinity than the standard drug (acarbose).
UNASSIGNED: Overall, the butanol and ethyl acetate fractions of S. mombin stem bark ameliorate type 2 diabetes in Drosophila. However, further studies are needed in other animal models to confirm the antidiabetes effect of the plant.
UNASSIGNED: ارتبط ظهور مرض السكري المقاوم للأنسولين بنظام غذائي عالي السكروز في الفقاريات واللافقاريات. من ناحية أخرى، تم الإبلاغ عن أن جزءا مختلفا من نبات \"سبوندياس مومبين\" يمتلك إمكانات مضادة لمرض السكري. ومع ذلك، لم يتم استكشاف الفعالية المضادة لمرض السكري لحاء جذع \"سبوندياس مومبين\" في نظام غذائي عالي السكروز الناجم عن نموذج ذبابة الفاكهة السوداء البطن. في هذه الدراسة الحالية، تم إجراء التأثيرات المضادة للسكري ومضادات الأكسدة لكسور المذيبات من اللحاء.
UNASSIGNED: تم إجراء تجزئة متتالية لمستخلص الإيثانول لحاء الساق \"سبوندياس مومبين\" وتم إخضاع الكسور الناتجة لمقايسات مضادات الأكسدة ومضادات السكري في المختبر باستخدام البروتوكولات القياسية. تم تثبيت المركبات النشطة التي تم تحديدها باستخدام جهاز الاستشراب السائل الرفيع الإنجاز لدراسة جزء \"بيوتانول\" على الموقع النشط لـ \"ألفا-أميلاز\" في ذبابة الفاكهة باستخدام برنامج \"أوتودوك\" لمحاكاة النمذجة الجزيئية. تم دمج أجزاء \"بيوتانول\" و \" إيثيل الأسيتات\" من النبات في النظام الغذائي لمرض السكري والذباب غير المصاب بالسكري لدراسة الخصائص المضادة لمرض السكري ومضادات الأكسدة في الجسم الحي.
UNASSIGNED: أظهرت النتائج التي تم الحصول عليها أن جزيئات \"ن-بيوتانول\" و \"إيثيل الأسيتات\" تمتلك أعلى قدرة مضادة للأكسدة في المختبر عن طريق تثبيط \"دي.بي.بي.اتش\" و \"اف.آر.أ.بي\" وجذر الهيدروكسيل متبوعا بتثبيط معنوي لـ \"ألفا-أميلاز\". يكشف تحليل الاستشراب السائل الرفيع الإنجاز عن تحديد ثمانية مركبات تحتوي على كيرسيتين ذات أعلى قمة تليها روتين، ورامنيتين، وحمض الكلوروجينيك، وزينوكسانثين، ولوتين، وإيزوكيرسيتين، وروتينوز تظهر أدنى قمة. أعادت الكسور اختلال توازن الجلوكوز ومضادات الأكسدة في داء السكري وهو ما يمكن مقارنته بالعقار القياسي (الميتفورمين). كانت الكسور أيضا قادرة على تنظيم تعبير \"آي.ال.بي-2\" و \"آي.ان.ار\" و \"آي.ام.بي.ال2\" في ذباب السكري. كشفت دراسات السيليكو عن القدرة التثبيطية للمركبات النشطة ضد الأميلاز مع أيزوكيرسيتين، ورامنيتين، وروتين، وكيرسيتين، وحمض الكلوروجينيك التي لها تقارب ارتباط أعلى من الدواء القياسي (أكاربوز).
UNASSIGNED: بشكل عام، تعمل كسور البيوتانول والإيثيل أسيتات من لحاء \"سبوندياس مومبين\" على تحسين مرض السكري من النوع 2 في ذبابة الفاكهة. ومع ذلك، تم اقتراح مزيد من الدراسة المضادة للسكري في نموذج حيواني آخر لتكمل هذه النتيجة.

BACKGROUND: The bulk metallic glass (BMG), Pd79Ag3.5P6Si9.5Ge2, has a high fracture toughness and has been found to accommodate post-yield stress, unlike most other BMG. Moreover, due to its greater noble gas composition it has a intrinsic corrosion resistance, ideal for dental and orthopedic implants.
OBJECTIVE: This present study aimed to evaluate the in vivo application of Pd79Ag3.5P6Si9.5Ge2 in a large translational sheep model to assess its efficacy to be utilized as an endosteal device.
METHODS: Twelve implants in the form of cylindrical rods (3 mm in diameter) were produced through rapid quenching. Each sheep (n = 12) received one osteotomy in the mandibular region using rotary instrumentation, which was filled with Pd79Ag3.5P6Si9.5Ge2. After 6- and 24-weeks the animals were euthanized, and samples collected en bloc to conduct histomorphometric analysis. The degree of osseointegration were assessed through bone-to-implant contact (BIC).
RESULTS: All samples revealed favorable BIC along with with fibrous connective tissue layers at both 6- and 24-weeks. Bone along with interfacial remodeling was observed in proximity with the metallic glass surface at 6 weeks with higher degrees of bone organization being observed at the later healing time, 24 weeks.
CONCLUSIONS: The synthesized BMG, given its unique combination of toughness and strength, revealed potential to serve as an alternative to commonly used Ti alloys.

BACKGROUND: There is minimal literature on the anatomic factors associated with partial distal biceps tendon (DBT) tears. It has been proposed that a larger radial tuberosity size-and, therefore, a smaller radioulnar space during pronation-may cause mechanical impingement of the DBT predisposing to tears. We sought to investigate the anatomic factors that may be associated with partial DBT tears by retrospectively reviewing the DBT anatomy using 3-T magnetic resonance imaging (MRI) scans of elbows with partial DBT tears and a comparison group of normal elbows.
METHODS: Two independent observers retrospectively reviewed 3-T MRI scans of elbows with partial DBT tears and elbows without visible pathology. Basic demographic data were collected, and measurements of radial tuberosity length, radial tuberosity thickness, radioulnar space, and radial tuberosity-ulnar space were made using simultaneous tracker lines and a standardized technique. The ratio of radial tuberosity thickness to radial diameter and the ratio of radioulnar space to radial tuberosity-ulnar space were calculated. The presence or absence of enthesophytes and the presence of a single DBT vs. double DBTs were noted.
RESULTS: This study included twenty-six 3-T MRI scans of 26 elbows with partial DBT tears and thirty 3-T MRI scans of 30 elbows without pathology. Basic demographic data were comparable between the 2 groups. The tear group showed statistically significantly larger mean measurements for radial tuberosity length (24.3 mm vs. 21.3 mm, P = .002) and radial tuberosity thickness (5.5 mm vs. 3.7 mm, P < .0001). The tear group also showed statistically significantly smaller measurements for radioulnar space (8.2 mm vs. 10.0 mm, P = .010) and radial tuberosity-ulnar space (7.2 mm vs. 9.1 mm, P = .013). The ratio of radial tuberosity thickness to radial diameter was statistically significantly larger in the tear group (0.389 vs. 0.267, P < .0001). There was a statistically significant positive correlation between partial DBT tears and the presence of enthesophytes (P = .007), as well as between partial DBT tears and the presence of 2 discrete DBTs rather than a single tendon or 2 DBTs that interdigitated prior to insertion (P < .0001).
CONCLUSIONS: Larger radial tuberosities and smaller radioulnar and radial tuberosity-ulnar spaces are associated with partial DBT tears. Larger tuberosities and a smaller functional space for the DBT may lead to chronic impingement, tendon delamination, and consequent weakness, which ultimately lead to tears. Enthesophytes may be associated with tears for the same reason. The presence of 2 discrete DBTs that do not interdigitate prior to insertion is also associated with partial tears. This study will help clinicians understand the pathogenesis of partial DBT tears.

BACKGROUND: On the basis of the current literature, the optimal surgical technique for distal biceps tendon tears remains controversial. Cadaveric studies have investigated distal biceps anatomy but are limited by cohort size and tissue factors. We sought to investigate distal biceps anatomy in vivo by retrospectively reviewing magnetic resonance imaging (MRI) scans. An improved understanding of the anatomy of the distal biceps tendon will lead to better definition of the optimal anatomic surgical repair.
METHODS: Two independent observers retrospectively reviewed 3-T MRI scans of elbows. Basic demographic data were collected, and measurements of tendon length, footprint width, footprint length, and footprint angle were taken using simultaneous tracker lines and a standardized technique. From the biceps muscle belly distally, the presence of a single tendon or double tendons was recorded and the tendon interdigitation point was measured if relevant.
RESULTS: A total of 106 3-T MRI scans of 106 elbows of 103 patients were included. There were 71 male and 32 female patients, and the mean age was 44.7 years. Most distal biceps tendons exited the biceps muscle belly as separate entities (91%, 96 of 106 elbows) and then coalesced prior to insertion on the radial tuberosity (91%, 87 of 96 elbows). There was a positive correlation between tendon length and footprint length (P < .05), as well as between tendon length and footprint width (P < .05). The mean tendon length was 65.2 mm (95% confidence interval [CI], 63.3-66.8 mm; range, 44.3-86.8 mm), the mean distance from the musculotendinous junction to the interdigitation point was 38.3 mm (95% CI, 35.8-40.9 mm; range, 8.9-64.8 mm), the mean footprint width was 10.3 mm (95% CI, 9.9-10.7 mm; range, 5.9-16.3 mm), the mean footprint length was 16.2 mm (95% CI, 15.6-16.9; range, 7.3-25.4 mm), and the mean footprint angle was 32.1° (95% CI, 29.5°-34.6°; range, 8.5°-84.3°).
CONCLUSIONS: An in vivo, high-resolution study of the anatomy of the distal biceps tendon improves our understanding of its complex morphology and hence our ability to perform an anatomic \"footprint repair.\"

Four series of hypoxia-inducible factor-1 alpha (HIF-1α) functioning derivatives stemming from modifications to the C-29 carboxyl group of celastrol were designed and synthesized, and their anticancer activities were evaluated. To address the structure and activity relationship of each derivative, extensive structural changes were made. HRE luciferase reporter assay demonstrated that 12 modified compounds showed superior HIF-1α inhibitory activity. Among them, compound C6 exhibited the best features: firstly, the strongest HIF-1α inhibitory activity (IC50 = 0.05 μM, 5-fold higher than that of celastrol); secondly, lower cytotoxicity (22-fold lower, C6-16.85 μM vs celastrol-0.76 μM). Thus, the safety factor of C6 was about 112 times higher than that of celastrol. Western blot assay indicated that C6 may inhibit the expression of HIF-1α protein in cells. Additionally, C6 hindered tumor cell cloning, migration and induced cell apoptosis. It is worth mentioning that in the mouse tumor xenograft model, C6 (10 mg/kg) displayed good antitumor activity in vivo, showing a better inhibition rate (74.03%) than the reference compound 5-fluorouracil (inhibition rate, 59.58%). However, the celastrol treatment group experienced collective death after four doses of the drug. Moreover, C6 minimally affected the mouse weight, indicating that its application in vivo has little toxic effect. H&E staining experiments show that it could also exacerbate the degree of tumor cell damage. The results of water solubility experiment show that the solubility of C6 is increased by 1.36 times than that of celastrol. In conclusion, C6 is a promising antitumor agent through HIF-1α pathway.

OBJECTIVE: To evaluate the contact area of the radiocapitellar joint with forearm pronation and supination under axial loading.
METHODS: Six healthy volunteers (2 males and 4 females, mean age: 44.6 years) were included in the study. A computed tomography scan of the extended elbow joints was obtained at 4 positions of forearm: full pronation with or without load and full supination with or without load. Mimics, 3-matic Medical, Geomagic, and Photoshop were used to reconstruct 3-dimensional models. The contact area of the radiocapitellar joint was measured. Shifting of the center of the contact area of the radiocapitellar joint was measured.
RESULTS: The axial load added 8.6% and 10.5% contact area to pronation and supination without load, respectively. From pronation without load, the center of contact area significantly shifted 2.4 ± 1.1 mm anteromedially to supination without load and shifted by 1.0 ± 0.5 mm to the center of the radial head compared with the pronation with load. The center of the contact area significantly shifted 2.4 ± 1.5 mm anteromedially from the pronation to the supination under loading. The contact area of the tuberosity anterior in the radial head significantly increased by 14% (without load) and 8% (with load) from pronation to supination.
CONCLUSIONS: Axial loading increases the contact area of the radiocapitellar joint. The center of the contact area of the radiocapitellar joint changed according to loading and shifted to the anterior tuberosity of the radial head from forearm pronation to supination.

Here, we formulated and investigated the structure-activity relationships of novel N-substituted carbazole sulfonamide derivatives with improved physicochemical properties. Most of these new compounds displayed good aqueous solubility. Certain molecules presented strong in vitro antiproliferative and in vivo antitumor activity. Relative to the control, 50 mg/kg compound 3v substantially reduced human HepG2 xenograft mouse tumor growth by 54.5% and its efficacy was comparable to that of CA-4P. Compound 3h demonstrated anticancer efficacy in both subcutaneous and orthotopic HepG2 xenograft mouse models. We also developed a novel synthetic method for 7-hydroxy-substituted carbazole sulfonamides. Compared with the control, 25 mg/kg compound 4c inhibited human HepG2 xenograft mouse tumor growth by 71.7% and was more potent than 50 mg/kg CA-4P with only 50% tumor shrinkage efficacy. Among the three water-soluble carbazole sulfonamide derivatives formulated in the present study, compound 4c displayed the most effective tumor growth inhibition in vivo and merit further investigation as potential antitumor agents for cancer therapy.