Promotion of Bone Formation in a Rat Osteoporotic Vertebral Body Defect Model via Suppression of Osteoclastogenesis by Ectopic Embryonic Calvaria Derived Mesenchymal Stem Cells.

Osteoporotic vertebral compression fractures (OVCFs) are the most prevalent fractures among patients with osteoporosis, leading to severe pain, deformities, and even death. This study explored the use of ectopic embryonic calvaria derived mesenchymal stem cells (EE-cMSCs), which are known for their superior differentiation and proliferation capabilities, as a potential treatment for bone regeneration in OVCFs. We evaluated the impact of EE-cMSCs on osteoclastogenesis in a RAW264.7 cell environment, which was induced by the receptor activator of nuclear factor kappa-beta ligand (RANKL), using cytochemical staining and quantitative real-time PCR. The osteogenic potential of EE-cMSCs was evaluated under various hydrogel conditions. An osteoporotic vertebral body bone defect model was established by inducing osteoporosis in rats through bilateral ovariectomy and creating defects in their coccygeal vertebral bodies. The effects of EE-cMSCs were examined using micro-computed tomography (µCT) and histology, including immunohistochemical analyses. In vitro, EE-cMSCs inhibited osteoclast differentiation and promoted osteogenesis in a 3D cell culture environment using fibrin hydrogel. Moreover, µCT and histological staining demonstrated increased new bone formation in the group treated with EE-cMSCs and fibrin. Immunostaining showed reduced osteoclast activity and bone resorption, alongside increased angiogenesis. Thus, EE-cMSCs can effectively promote bone regeneration and may represent a promising therapeutic approach for treating OVCFs.

Morphogenetic Designs, and Disease Models in Central Nervous System Organoids.

Since the emergence of the first cerebral organoid (CO) in 2013, advancements have transformed central nervous system (CNS) research. Initial efforts focused on studying the morphogenesis of COs and creating reproducible models. Numerous methodologies have been proposed, enabling the design of the brain organoid to represent specific regions and spinal cord structures. CNS organoids now facilitate the study of a wide range of CNS diseases, from infections to tumors, which were previously difficult to investigate. We summarize the major advancements in CNS organoids, concerning morphogenetic designs and disease models. We examine the development of fabrication procedures and how these advancements have enabled the generation of region-specific brain organoids and spinal cord models. We highlight the application of these organoids in studying various CNS diseases, demonstrating the versatility and potential of organoid models in advancing our understanding of complex conditions. We discuss the current challenges in the field, including issues related to reproducibility, scalability, and the accurate recapitulation of the in vivo environment. We provide an outlook on prospective studies and future directions. This review aims to provide a comprehensive overview of the state-of-the-art CNS organoid research, highlighting key developments, current challenges, and prospects in the field.

Prognostic Effect of Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated Gastric Carcinomas Measured by Digital Image Analysis.

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is characterized by prominent tumor-infiltrating lymphocytes (TILs) and has a favorable prognosis. Tertiary lymphoid structures (TLS), characterized by ectopic aggregated lymphocytes with high-endothelial venules (HEV), are associated with favorable outcomes in various solid tumors. We hypothesized that EBVaGC, characterized by intense TILs, may be closely associated with TLS or HEV. To test this hypothesis, we digitally analyzed the TLS, HEV, and TILs in 73 surgically resected advanced EBVaGCs. For HEV, dual MECA-79 and CD31 dual immunohistochemistry were performed, and the ectopic expression of MECA-79 in tumor cells was measured. In 73 patients with EBVaGC, a high-TLS ratio was found in 29 (39.7%) cases, high-tumor-associated HEV density in 44 (60.3%) cases, and high-CD8+ TIL density in 38 (52.1%) cases. Ectopic tumor expression of MECA-79 was observed in 36 patients (49.3%) cases. A low-TLS ratio and tumor-associated HEV density were significantly associated with lymph node metastasis (P = .005 and .042, respectively). Ectopic MECA-79 expression was significantly associated with lymph node metastasis (P = .003). Patients with a low-TLS ratio (P = .038), low-HEV density (P = .042), and ectopic tumor MECA-79 expression (P = .032) had significantly worse prognoses. In conclusion, TLS ratio and HEV density affect the survival of patients with EBVaGC and may be related to the immune response that interrupts lymph node metastasis.

Data pipeline for real-time energy consumption data management and prediction.

With the increasing utilization of data in various industries and applications, constructing an efficient data pipeline has become crucial. In this study, we propose a machine learning operations-centric data pipeline specifically designed for an energy consumption management system. This pipeline seamlessly integrates the machine learning model with real-time data management and prediction capabilities. The overall architecture of our proposed pipeline comprises several key components, including Kafka, InfluxDB, Telegraf, Zookeeper, and Grafana. To enable accurate energy consumption predictions, we adopt two time-series prediction models, long short-term memory (LSTM), and seasonal autoregressive integrated moving average (SARIMA). Our analysis reveals a clear trade-off between speed and accuracy, where SARIMA exhibits faster model learning time while LSTM outperforms SARIMA in prediction accuracy. To validate the effectiveness of our pipeline, we measure the overall processing time by optimizing the configuration of Telegraf, which directly impacts the load in the pipeline. The results are promising, as our pipeline achieves an average end-to-end processing time of only 0.39 s for handling 10,000 data records and an impressive 1.26 s when scaling up to 100,000 records. This indicates 30.69-90.88 times faster processing compared to the existing Python-based approach. Additionally, when the number of records increases by ten times, the increased overhead is reduced by 3.07 times. This verifies that the proposed pipeline exhibits an efficient and scalable structure suitable for real-time environments.

Synergistic Renoprotective Effects of Green Tea Extract and Gemigliptin against Tacrolimus-Induced Nephrotoxicity in Mice / Efectos Renoprotectores Sinérgicos del Extracto de Té Verde y Gemigliptina contra la Nefrotoxicidad Inducida por Tacrolimus en Ratones

SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.

Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.

Structurally Aligned Multifunctional Neural Probe (SAMP) Using Forest-Drawn CNT Sheet onto Thermally Drawn Polymer Fiber for Long-Term In Vivo Operation.

Neural probe engineering is a dynamic field, driving innovation in neuroscience and addressing scientific and medical demands. Recent advancements involve integrating nanomaterials to improve performance, aiming for sustained in vivo functionality. However, challenges persist due to size, stiffness, complexity, and manufacturing intricacies. To address these issues, a neural interface utilizing freestanding CNT-sheets drawn from CNT-forests integrated onto thermally drawn functional polymer fibers is proposed. This approach yields a device with structural alignment, resulting in exceptional electrical, mechanical, and electrochemical properties while retaining biocompatibility for prolonged periods of implantation. This Structurally Aligned Multifunctional neural Probe (SAMP) employing forest-drawn CNT sheets demonstrates in vivo capabilities in neural recording, neurotransmitter detection, and brain/spinal cord circuit manipulation via optogenetics, maintaining functionality for over a year post-implantation. The straightforward fabrication method's versatility, coupled with the device's functional reliability, underscores the significance of this technique in the next-generation carbon-based implants. Moreover, the device's longevity and multifunctionality position it as a promising platform for long-term neuroscience research.

Extended-Spectrum Beta-Lactamase Escherichia coli-Associated Acute Cholangitis: Uncommon Patient Characteristics and Clinical Implications.

Acute cholangitis is a potentially life-threatening condition caused by an infection of the biliary tract resulting from biliary obstruction. This case report highlights an unusual presentation of acute cholangitis in an elderly patient characterized by the presence of extended-spectrum beta-lactamase-producing Escherichia coli. We aim to emphasize the significance of recognizing diverse clinical manifestations in the elderly population to enhance timely diagnosis and appropriate management. The case highlights the importance of better understanding patient risk factors for potential causative organisms and their susceptibility to selecting proper antibiotics and improving clinical outcomes.

Suicidal ideation and attempt among young people living in gosiwons in South Korea.

INTRODUCTION: Young people living in gosiwons could be at high risk for suicide owing to inadequate living conditions and the social stigma towards them. However, this topic has not received adequate academic attention. Gosiwon is a type of small residence consisting of several tiny rooms densely packed together and usually does not meet minimum housing standards. However, gosiwons are favored by low-income groups, especially young people, because they are cheaper than other residences. This study aimed to examine the factors that increase the risk of suicidal ideation and attempt among young people living in gosiwons. METHODS: A sample of 300 young people aged 19-34 years living in gosiwons for over 6 months was analyzed. A set of multinomial logistic regression was conducted to examine the factors that differentiate the suicidal ideation and attempt group from the no-suicidal risk group. RESULTS: Approximately 30% of the study participants experienced suicidal ideation or attempted suicide. Among several risk factors, social exclusion and depressive symptoms distinguished the group with suicidal ideation from the no-risk group. Depressive symptoms were the only factor that differentiated the group with suicide attempts history from the no-risk group. CONCLUSION: The results emphasize the need to focus on social exclusion and depressive symptoms among young people living in poor housing conditions. Interventions to address social exclusion and depressive symptoms may help prevent suicide risk among young people exposed to housing exclusion.

Angiogenesis-on-a-chip coupled with single-cell RNA sequencing reveals spatially differential activations of autophagy along angiogenic sprouts.

Several functions of autophagy associated with proliferation, differentiation, and migration of endothelial cells have been reported. Due to lack of models recapitulating angiogenic sprouting, functional heterogeneity of autophagy in endothelial cells along angiogenic sprouts remains elusive. Here, we apply an angiogenesis-on-a-chip to reconstruct 3D sprouts with clear endpoints. We perform single-cell RNA sequencing of sprouting endothelial cells from our chip to reveal high activation of autophagy in two endothelial cell populations- proliferating endothelial cells in sprout basements and stalk-like endothelial cells near sprout endpoints- and further the reciprocal expression pattern of autophagy-related genes between stalk- and tip-like endothelial cells near sprout endpoints, implying an association of autophagy with tip-stalk cell specification. Our results suggest a model describing spatially differential roles of autophagy: quality control of proliferating endothelial cells in sprout basements for sprout elongation and tip-stalk cell specification near sprout endpoints, which may change strategies for developing autophagy-based anti-angiogenic therapeutics.

Hemorrhagic Complications Following Ultrasound-Guided Breast Biopsy: A Prospective Patient-Centered Study.

OBJECTIVE: We aimed to evaluate the clinical and imaging factors associated with hemorrhagic complications and patient discomfort following ultrasound (US)-guided breast biopsy. MATERIALS AND METHODS: We prospectively enrolled 94 patients who were referred to our hospital between June 2022 and December 2022 for US-guided breast biopsy. After obtaining informed consent, two breast radiologists independently performed US-guided breast biopsy and evaluated the imaging findings. A hemorrhagic complication was defined as the presence of bleeding or hematoma on US. The patients rated symptoms of pain, febrile sensation, swelling at the biopsy site, and dyspnea immediately, 20 minutes, and 2 weeks after the procedure on a visual analog scale, with 0 for none and 10 for the most severe symptoms. Additional details recorded included those of nausea, vomiting, bleeding, bruising, and overall satisfaction score. We compared the clinical symptoms, imaging characteristics, and procedural features between patients with and those without hemorrhagic complications. RESULTS: Of 94 patients, 7 (7%) developed hemorrhagic complications, while 87 (93%) did not. The complication resolved with 20 minutes of manual compression, and no further intervention was required. Vascularity on Doppler examination (P = 0.008), needle type (P = 0.043), and lesion location (P < 0.001) were significantly different between the groups. Patients with hemorrhagic complications reported more frequent nausea or vomiting than those without hemorrhagic complications (29% [2/7] vs. 2% [2/87], respectively; P = 0.027). The overall satisfaction scores did not differ between the two groups (P = 0.396). After 2 weeks, all symptoms subsided, except bruising (50% 2/4 in the complication group and 25% [16/65] in the no-complication group). CONCLUSION: US-guided breast biopsy is a safe procedure with a low complication rate. Radiologists should be aware of hemorrhagic complications, patient discomfort, and overall satisfaction related to this procedure.

Nanoscale Magneto-mechanical-genetics of Deep Brain Neurons Reversing Motor Deficits in Parkinsonian Mice.

Here, we introduce the magneto-mechanical-genetic (MMG)-driven wireless deep brain stimulation (DBS) using magnetic nanostructures for therapeutic benefits in the mouse model of Parkinson's disease (PD). Electrical DBS of the subthalamic nucleus (STN) is an effective therapy for mitigating Parkinson's motor symptoms. However, its broader application is hampered by the requirement for implanted electrodes and the lack of anatomical and cellular specificity. Using the nanoscale magnetic force actuators (m-Torquer), which deliver torque force under rotating magnetic fields to activate pre-encoded Piezo1 ion channels on target neurons, our system enables wireless and STN-specific DBS without implants, addressing key unmet challenges in the DBS field. In both late- and early-stage PD mice, MMG-DBS significantly improved locomotor activity and motor balance by 2-fold compared to untreated PD mice. Moreover, MMG-DBS enabled sustained therapeutic effects. This approach provides a non-invasive and implant-free DBS with cellular targeting capability for the effective treatment of Parkinsonian symptoms.

Association between Neck Circumference and Chronic Kidney Disease in Korean Adults in the 2019-2021 Korea National Health and Nutrition Examination Survey.

Chronic kidney disease (CKD) is a major public health problem and a leading cause of cardiovascular disease and death. Early recognition and management of CKD risk factors are necessary to prevent its onset and progression. Neck circumference (NC) is a non-invasive and easily accessible anthropometric measure associated with central obesity and subcutaneous fat accumulation in the upper body. Our study aimed to explore the relationship between NC and the prevalence of CKD using data from the nationally representative Korea National Health and Nutrition Examination Survey (2019-2021). We analyzed data from 10,219 subjects (age > 19 years, no missing values). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Logistic regression analysis was performed, which revealed a significant association between NC and CKD prevalence even after adjusting for confounding factors, both when NC was considered a continuous variable (OR [95% CI], 1.11 [1.03-1.19]) and in quartiles (Q1 as reference; Q2 OR [95% CI], 1.23 [0.91-1.67]; Q3 OR [95% CI], 1.59 [1.16-2.18]; Q4 OR [95% CI], 1.70 [1.16-2.50]). Our findings suggest that NC could be a simple and effective anthropometric measurement for identifying individuals at risk for CKD.

The CLAMP GA-binding transcription factor regulates heat stress-induced transcriptional repression by associating with 3D loop anchors.

In order to survive when exposed to heat stress (HS), organisms activate stress response genes and repress constitutive gene expression to prevent the accumulation of potentially toxic RNA and protein products. Although many studies have elucidated the mechanisms that drive HS-induced activation of stress response genes across species, little is known about repression mechanisms or how genes are targeted for activation versus repression context-specifically. The mechanisms of heat stress-regulated activation have been well-studied in Drosophila, in which the GA-binding transcription factor GAF is important for activating genes upon heat stress. Here, we show that a functionally distinct GA-binding transcription factor (TF) protein, CLAMP (Chromatin-linked adaptor for MSL complex proteins), is essential for repressing constitutive genes upon heat stress but not activation of the canonical heat stress pathway. HS induces loss of CLAMP-associated 3D chromatin loop anchors associated with different combinations of GA-binding TFs prior to HS if a gene becomes repressed versus activated. Overall, we demonstrate that CLAMP promotes repression of constitutive genes upon HS, and repression and activation are associated with the loss of CLAMP-associated 3D chromatin loops bound by different combinations of GA-binding TFs.

Drug-Eluting Bead Transarterial Chemoembolization Versus Radiofrequency Ablation as an Initial Treatment of Single Small (≤ 3 cm) Hepatocellular Carcinoma.

BACKGROUND: In this study, we aimed to compare the long-term therapeutic outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) with those of radiofrequency ablation (RFA) for the initial treatment of a single small (≤ 3 cm) hepatocellular carcinoma (HCC). METHODS: From January 2010 to December 2021, 259 consecutive patients who underwent DEB-TACE (67 patients) or RFA (192 patients) as a first-line treatment for a single small HCC were enrolled in this retrospective study. The therapeutic outcomes, including cumulative intrahepatic local tumor progression (LTP), progression-free survival (PFS), and long-term overall survival (OS) rates, were compared between the two groups before and after propensity score (PS) matching. Multivariate Cox proportional hazard models were used to evaluate the prognostic factors and differences in OS and PFS between the two groups for all 92 patients after PS matching. RESULTS: After PS matching, the 1-, 2-, 3-, and 5-year LTP rates were lower in the RFA group than those in the DEB-TACE group (P < 0.001), and the 1-, 2-, 3-, and 5-year PFS rates in the RFA group were higher than those in the DEB-TACE group (P = 0.007). However, the 1-, 2-, 3-, and 5-year OS rates were not significantly different between the RFA and DEB-TACE groups (P = 0.584). Moreover, the OS was not significantly different between the RFA and DEB-TACE groups in the univariate and multivariate analyses, with a hazard ratio (HR) of 0.81. The PFS was significantly higher in the RFA group than that in the DEB-TACE group in the univariate analyses, with a HR of 0.44 (P = 0.009). Multivariate Cox regression analysis showed that albumin (P = 0.019) was an independent prognostic factor for OS. Additionally, the major complication rates were not significantly different between the DEB-TACE and RFA groups (P = 1.000). CONCLUSION: The LTP and PFS rates of RFA were superior to those of DEB-TACE in the initial treatment of single small HCC after PS matching. However, the OS rates were not significantly different between RFA and DEB-TACE. Therefore, DEB-TACE may be considered an efficient substitute for RFA in some patients with a single small HCC who are ineligible for RFA.

Liquefied Lung Cancer: An Uncommon Form of Squamous Cell Carcinoma of the Lung.

Lung cancer is a significant global health concern, with high incidence and mortality rates. This case report presents the atypical presentation of a 71-year-old female with a history of lung cancer who initially presented with symptoms suggestive of infection secondary to a liquefied lung malignancy and later developed bronchial obstruction. Diagnosis of lung cancer requires a high level of clinical suspicion, and imaging techniques, such as PET and CT scans, provide additional evidence. However, necrotic lesions do not have specific findings on radiology. Treatment options depend on the cancer stage, with surgical resection being the primary approach. Chemotherapy and radiation are used for unresectable cases. Liquefied lung cancer is associated with poor outcomes. Post-obstructive pneumonia with necrotic lesions, particularly in cases without an underlying organism, is a relatively rare phenomenon in lung cancer that requires further investigation. Large-scale studies are needed to explore this aspect further and enhance our understanding of lung cancer complications.

Phenotypic and molecular basis of SIX1 variants linked to non-syndromic deafness and atypical branchio-otic syndrome in South Korea.

Branchio-oto-renal (BOR)/branchio-otic (BO) syndrome is a rare disorder and exhibits clinically heterogenous phenotypes, marked by abnormalities in the ear, branchial arch, and renal system. Sporadic cases of atypical BOR/BO syndrome have been recently reported; however, evidence on genotype-phenotype correlations and molecular mechanisms of those cases is lacking. We herein identified five SIX1 heterozygous variants (c.307dupC:p.Leu103Profs*51, c.373G>A:p.Glu125Lys, c.386_391del:p.Tyr129_Cys130del, c.397_399del:p.Glu133del, and c.501G>C:p.Gln167His), including three novel variants, through whole-exome sequencing in five unrelated Korean families. All eight affected individuals with SIX1 variants displayed non-syndromic hearing loss (DFNA23) or atypical BO syndrome. The prevalence of major and minor criteria for BOR/BO syndrome was significantly reduced among individuals with SIX1 variants, compared to 15 BOR/BO syndrome families with EYA1 variants. All SIX1 variants interacted with the EYA1 wild-type; their complexes were localized in the nucleus except for the p.Leu103Profs*51 variant. All mutants also showed obvious but varying degrees of reduction in DNA binding affinity, leading to a significant decrease in transcriptional activity. This study presents the first report of SIX1 variants in South Korea, expanding the genotypic and phenotypic spectrum of SIX1 variants, characterized by DFNA23 or atypical BO syndrome, and refines the diverse molecular aspects of SIX1 variants according to the EYA1-SIX1-DNA complex theory.

Phase intensity nanoscope (PINE) opens long-time investigation windows of living matter.

Fundamental to all living organisms and living soft matter are emergent processes in which the reorganization of individual constituents at the nanoscale drives group-level movements and shape changes at the macroscale over time. However, light-induced degradation of fluorophores, photobleaching, is a significant problem in extended bioimaging in life science. Here, we report opening a long-time investigation window by nonbleaching phase intensity nanoscope: PINE. We accomplish phase-intensity separation such that nanoprobe distributions are distinguished by an integrated phase-intensity multilayer thin film (polyvinyl alcohol/liquid crystal). We overcame a physical limit to resolve sub-10 nm cellular architectures, and achieve the first dynamic imaging of nanoscopic reorganization over 250 h using PINE. We discover nanoscopic rearrangements synchronized with the emergence of group-level movements and shape changes at the macroscale according to a set of interaction rules with importance in cellular and soft matter reorganization, self-organization, and pattern formation.

Novel Therapies for Celiac Disease: A Clinical Review Article.

Celiac disease is emerging as an autoimmune disorder with increasing prevalence and incidence. The mean age of presentation is also increasing with the passage of time. The delay in diagnosis is partly attributable to the asymptomatic state in which most patients present. The diagnosis of the disease is primarily based on biopsy, but serology can also be included for possible screening purposes. Although the primary management strategy is to eliminate gluten from the diet of such patients; however, compliance with the diet and follow-up to detect healing might be difficult to maintain. Therefore, there is a need to investigate further management therapies that can be easily administered and monitored. The aim of the review is to discuss the epidemiology, clinical presentation, and novel therapies being investigated for celiac disease.

Lidocaine-loaded dissolving microneedle for safe local anesthesia on oral mucosa for dental procedure.

BACKGROUND: Lidocaine has been widely used as a short-acting local anesthetic agent to reduce the pain caused by needle insertion. Dissolving microneedles (DMNs), which are minimally invasive, can effectively deliver drugs by overcoming the oral mucosal barrier and relieving patient discomfort. METHODS: Lidocaine solution prepared by mixing lidocaine-HCl and hyaluronic acid was used to fabricate oral lidocaine HCl-encapsulated DMNs (oral Li-DMNs) via centrifugal lithography. The dissolution, penetration ability, and local transmucosal drug delivery of oral Li-DMNs into the oral mucosa were evaluated in porcine jaws. Pharmacokinetic analysis and safety assessment were performed using rabbits. RESULTS: The insertion depth of the oral Li-DMNs satisfies the safety standard. The oral Li-DMNs were completely dissolved after 3 min of application. The local transmucosal drug delivery, pharmacokinetic, and safety evaluations showed that the oral Li-DMNs can obtain a local anesthesia effect at a relatively lower dose, and there was no oral mucosal irritation in rabbits. CONCLUSIONS: A novel and safe oral Li-DMNs have potential applications in large animals and clinical trials and would possibly enter the anesthesia market.