Adjunctive recombinant human parathyroid hormone agents for the treatment of medication-related osteonecrosis of the jaw: a report of three cases.

Teriparatide has been effective in treating people diagnosed with medication-related osteonecrosis of the jaw (MRONJ). However, its efficacy is not well established to be accepted as a standard of care. The objective of this paper was to investigate the efficacy of recombinant human parathyroid hormone for the treatment of MRONJ. We report three cases of MRONJ patients with osteoporosis as the primary disease who were treated with a teriparatide agent along with other adjunctive measures. Each patient was administered a teriparatide injection subcutaneously for 16 weeks, 36 weeks, or 60 weeks. Surgical intervention including partial resection, sequestrectomy, decortication, and saucerization took place during the teriparatide administration. Complete lesion resolution was identified clinically and radiographically in all three patients. In patients diagnosed with MRONJ, teriparatide therapy is an efficacious and safe therapeutic option to improve healing of bone lesions. These findings demonstrate that teriparatide in combination with another therapy, especially bone morphogenetic protein, platelet-rich fibrin, or antibiotic therapy, can be an effective protocol for MRONJ.

Protective effect of Tat fused HPCA protein on neuronal cell death caused by ischemic injury.

Background: Bain ischemia is a disease that occurs for various reasons, induces reactive oxygen species (ROS), and causes fatal damage to the nervous system. Protective effect of HPCA on ischemic injury has not been extensively studied despite its significance in regulating calcium homeostasis and promoting neuronal survival in CA1 region of the brain. Objective: We investigate the role of HPCA in ischemic injury using a cell-permeable Tat peptide fused HPCA protein (Tat-HPCA). Methods: Western blot analysis determined the penetration of Tat-HPCA into HT-22 cells and apoptotic signaling pathways. 5-CFDA, AM, DCF-DA, and TUNEL staining confirmed intracellular ROS production and DNA damage. The intracellular Ca2+ was measured in primary cultured neurons treated with H2O2. Protective effects were examined using immunohistochemistry and cognitive function tests by passive avoidance test and 8-arm radial maze test. Results: Tat-HPCA effectively penetrated into HT-22 cells and inhibited H2O2-induced apoptosis, oxidative stress, and DNA fragmentation. It also effectively inhibited phosphorylation of JNK and regulated the activation of Caspase, Bax, Bcl-2, and PARP, leading to inhibition of apoptosis. Moreover, Ca2+ concentration decreased in cells treated with Tat-HPCA in primary cultured neurons. In an animal model of ischemia, Tat-HPCA effectively penetrated the hippocampus, inhibited cell death, and regulated activities of astrocytes and microglia. Additionally, Cognitive function tests show that Tat-HPCA improves neurobehavioral outcomes after cerebral ischemic injury. Conclusion: These results suggest that Tat-HPCA might have potential as a therapeutic agent for treating oxidative stress-related diseases induced by ischemic injury, including ischemia.

2D-Material-Assisted GaN Growth on GaN Template by MOCVD and Its Exfoliation Strategy.

The production of freestanding membranes using two-dimensional (2D) materials often involves techniques such as van der Waals (vdW) epitaxy, quasi-vdW epitaxy, and remote epitaxy. However, a challenge arises when attempting to manufacture freestanding GaN by using these 2D-material-assisted growth techniques. The issue lies in securing stability, as high-temperature growth conditions under metal-organic chemical vapor deposition (MOCVD) can cause damage to the 2D materials due to GaN decomposition of the substrate. Even when GaN is successfully grown using this method, damage to the 2D material leads to direct bonding with the substrate, making the exfoliation of the grown GaN nearly impossible. This study introduces an approach for GaN growth and exfoliation on 2D material/GaN templates. First, graphene and hexagonal boron nitride (h-BN) were transferred onto the GaN template, creating stable conditions under high temperatures and various gases in MOCVD. GaN was grown in a two-step process at 750 and 900 °C, ensuring exfoliation in cases where the 2D materials remained intact. Essentially, while it is challenging to grow GaN on 2D material/GaN using only MOCVD, this study demonstrates that with effective protection of the 2D material, the grown GaN can endure high temperatures and still be exfoliated. Furthermore, these results support that vdW epitaxy and remote epitaxy principle are not only possible with specific equipment but also applicable generally.

Tat-CIAPIN1 Prevents Pancreatic ß-Cell Death in hIAPP-Induced RINm5F Cells and T2DM Animal Model.

It is well known that the cytokine-induced apoptosis inhibitor 1 (CIAPIN1) protein plays an important role in biological progresses as an anti-apoptotic protein. Human islet amyloid peptide (hIAPP), known as amylin, is caused to pancreatic ß-cell death in type 2 diabetes mellitus (T2DM). However, the function of CIAPIN1 protein on T2DM is not yet well studied. Therefore, we investigated the effects of CIAPIN1 protein on a hIAPP-induced RINm5F cell and T2DM animal model induced by a high-fat diet (HFD) and streptozotocin (STZ). The Tat-CIAPIN1 protein reduced the activation of mitogen-activated protein kinase (MAPK) and regulated the apoptosis-related protein expression levels including COX-2, iNOS, Bcl-2, Bax, and Caspase-3 in hIAPP-induced RINm5F cells. In a T2DM mice model, the Tat-CIAPIN1 protein ameliorated the pathological changes of pancreatic ß-cells and reduced the fasting blood glucose, body weight and hemoglobin Alc (HbAlc) levels. In conclusion, the Tat-CIAPIN1 protein showed protective effects against T2DM by protection of ß-cells via inhibition of hIAPP toxicity and by regulation of a MAPK signal pathway, suggesting CIAPIN1 protein can be a therapeutic protein drug candidate by beneficial regulation of T2DM.

Synergistic apoptosis by combination of metformin and an O-GlcNAcylation inhibitor in colon cancer cells.

BACKGROUND: Although autophagy is an important mediator of metformin antitumor activity, the role of metformin in the crosstalk between autophagy and apoptosis remains unclear. The aim was to confirm the anticancer effect by inducing apoptosis by co-treatment with metformin and OSMI-1, an inhibitor of O-GlcNAcylation, in colon cancer cells. METHODS: Cell viability was measured by MTT in colon cancer cell lines HCT116 and SW620 cells. Co-treatment with metformin and OSMI-1 induced autophagy and apoptosis, which was analyzed using western blot, reverse transcription-polymerase chain reaction (RT-PCR) analysis, and fluorescence-activated cell sorting (FACS). Combined treatment with metformin and OSMI-1 synergistically inhibit the growth of HCT116 was confirmed by xenograft tumors. RESULTS: We showed that metformin inhibited mammalian target of rapamycin (mTOR) activity by inducing high levels of C/EBP homologous protein (CHOP) expression through endoplasmic reticulum (ER) stress and activating adenosine monophosphate-activated protein kinase (AMPK) to induce autophagy in HCT116 cells. Interestingly, metformin increased O-GlcNAcylation and glutamine:fructose-6-phosphate amidotransferase (GFAT) levels in HCT116 cells. Thus, metformin also blocks autophagy by enhancing O-GlcNAcylation, whereas OSMI-1 increases autophagy via ER stress. In contrast, combined metformin and OSMI-1 treatment resulted in continuous induction of autophagy and disruption of O-GlcNAcylation homeostasis, resulting in excessive autophagic flux, which synergistically induced apoptosis. Downregulation of Bcl2 promoted apoptosis via the activation of c-Jun N-terminal kinase (JNK) and CHOP overexpression, synergistically inducing apoptosis. The activation of IRE1α/JNK signaling by OSMI-1 and PERK/CHOP signaling by metformin combined to inhibit Bcl2 activity, ultimately leading to the upregulation of cytochrome c release and activation of caspase-3. CONCLUSIONS: In conclusion, combinatorial treatment of HCT116 cells with metformin and OSMI-1 resulted in more synergistic apoptosis being induced by enhancement of signal activation through ER stress-induced signaling rather than the cell protective autophagy function. These results in HCT116 cells were also confirmed in xenograft models, suggesting that this combination strategy could be utilized for colon cancer treatment.

Intestinal Production of Alpha-Glucosidase Inhibitor by Bacillus coagulans Spores.

This study examines the possibility of directly producing and utilizing useful substances in the intestines of animals using anaerobic bacteria that can grow in the intestines of animals. A facultative anaerobe producing a large amount of α-glucosidase inhibitor was isolated from hay and identified and named Bacillus coagulans CC. The main compound of α-glucosidase inhibitor produced by Bacillus coagulans CC was identified as 1-deoxynojirimycin. α-glucosidase inhibitor activity was confirmed in the intestinal contents and feces of mice orally administered with spores of this strain, and it was confirmed that this strain could efficiently reach the intestines, proliferate, and produce α-glucosidase inhibitors. As a result of administering Bacillus coagulans CC to mice at 109 cells per 1 kg body weight of spores for 8 weeks, the high-carbohydrate diet and the high-fat diet showed a 5% lower weight gain compared to the non-administrated group. At this point, in the spore-administered group, a decrease was observed in both the visceral and subcutaneous fat layers of the abdomen and thorax in both high-carbohydrate and high-fat diet groups compared to the non-administered group on computed tomography. The results of this study show that α-glucosidase inhibitors produced in the intestine by specific strains can work efficiently.

Tat-RAN attenuates brain ischemic injury in hippocampal HT-22 cells and ischemia animal model.

Oxidative stress plays a key role in the pathogenesis of neuronal injury, including ischemia. Ras-related nuclear protein (RAN), a member of the Ras superfamily, involves in a variety of biological roles, such as cell division, proliferation, and signal transduction. Although RAN reveals antioxidant effect, its precise neuroprotective mechanisms are still unclear. Therefore, we investigated the effects of RAN on HT-22 cell which were exposed to H2O2-induced oxidative stress and ischemia animal model by using the cell permeable Tat-RAN fusion protein. We showed that Tat-RAN transduced into HT-22 cells, and markedly inhibited cell death, DNA fragmentation, and reactive oxygen species (ROS) generation under oxidative stress. This fusion protein also controlled cellular signaling pathways, including mitogen-activated protein kinases (MAPKs), NF-κB, and apoptosis (Caspase-3, p53, Bax and Bcl-2). In the cerebral forebrain ischemia animal model, Tat-RAN significantly inhibited both neuronal cell death, and astrocyte and microglia activation. These results indicate that RAN significantly protects against hippocampal neuronal cell death, suggesting Tat-RAN will help to develop the therapies for neuronal brain diseases including ischemic injury.

Protective effects of cell permeable Tat-PIM2 protein on oxidative stress induced dopaminergic neuronal cell death.

Background: Oxidative stress is considered as one of the main causes of Parkinson's disease (PD), however the exact etiology of PD is still unknown. Although it is known that Proviral Integration Moloney-2 (PIM2) promotes cell survival by its ability to inhibit formation of reactive oxygen species (ROS) in the brain, the precise functional role of PIM2 in PD has not been fully studied yet. Objective: We investigated the protective effect of PIM2 against apoptosis of dopaminergic neuronal cells caused by oxidative stress-induced ROS damage by using the cell permeable Tat-PIM2 fusion protein in vitro and in vivo. Methods: Transduction of Tat-PIM2 into SH-SY5Y cells and apoptotic signaling pathways were determined by Western blot analysis. Intracellular ROS production and DNA damage was confirmed by DCF-DA and TUNEL staining. Cell viability was determined by MTT assay. PD animal model was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and protective effects were examined using immunohistochemistry. Results: Transduced Tat-PIM2 inhibited the apoptotic caspase signaling and reduced the production of ROS induced by 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells. Furthermore, we confirmed that Tat-PIM2 transduced into the substantia nigra (SN) region through the blood-brain barrier and this protein protected the Tyrosine hydroxylase-positive cells by observation of immunohistostaining. Tat-PIM2 also regulated antioxidant biomolecules such as SOD1, catalase, 4-HNE, and 8-OHdG which reduce the formation of ROS in the MPTP-induced PD mouse model. Conclusion: These results indicated that Tat-PIM2 markedly inhibited the loss of dopaminergic neurons by reducing ROS damage, suggesting that Tat-PIM2 might be a suitable therapeutic agent for PD.

Six-month stability following extensive alveolar bone augmentation by sausage technique.

BACKGROUND: Resorption of alveolar bone is a common sequela of tooth loss and presents a clinical problem, especially in the esthetic zone. When ridge resorption occurs, adequate bone augmentation is essential to obtain satisfactory esthetic results. The purpose of this study was to determine the increase and retention rate of bone height or width in patients who received extensive bone augmentation and to analyze factors affecting its prognosis and stability. METHODS: This study was performed on patients who received extensive bone augmentation by sausage technique at the Department of Oral and Maxillofacial Surgery at Ewha Womans University Mok-dong Hospital from January 1, 2018, to February 28, 2022. CBCT images were taken before and 6 months after surgery to compare the amount of increase in bone height or width at the graft site. They were measured using reliable points such as adjacent implants or cephalometric landmarks, inferior alveolar nerve canals as reference points. RESULTS: A total of 8 patients underwent extensive bone grafting during the given period (mean age was 53.75 years, 2 males and 6 females). Four patients received horizontal augmentation, and 4 received vertical augmentation. When divided by surgical site, 4 patients are in maxilla and 4 in mandible. The average amount of increase in bone width or bone height was 5.38 mm, and the retention rate was about 79.9% after 6 months. The retention rate of horizontal augmentation was 88.8%, which was higher than that of vertical augmentation, which was 74.5%. The maxillary area accounted for 92.2%, and the amount of bone resorption was lower than that of the mandibular area, which was 72.6%. The average stitch out period was about 2.4 weeks, and postoperative dehiscence was observed about 37.5% of the total, more frequently in the mandible (50.0%) than in the maxilla (25.0%). CONCLUSION: In conclusion, extensive bone augmentation achieved significant horizontal or vertical bone height or width increase, and the retention rate after 6 months was also high. In addition, surgery in the maxillary region showed a more successful bone augmentation than in the mandible, with a higher maintenance rate and fewer cases of dehiscence.

Tat-GSTpi Inhibits Dopaminergic Cells against MPP+-Induced Cellular Damage via the Reduction of Oxidative Stress and MAPK Activation.

Glutathione S-transferase pi (GSTpi) is a member of the GST family and plays many critical roles in cellular processes, including anti-oxidative and signal transduction. However, the role of anti-oxidant enzyme GSTpi against dopaminergic neuronal cell death has not been fully investigated. In the present study, we investigated the roles of cell permeable Tat-GSTpi fusion protein in a SH-SY5Y cell and a Parkinson's disease (PD) mouse model. In the 1-methyl-4-phenylpyridinium (MPP+)-exposed cells, Tat-GSTpi protein decreased DNA damage and reactive oxygen species (ROS) generation. Furthermore, this fusion protein increased cell viability by regulating MAPKs, Bcl-2, and Bax signaling. In addition, Tat-GSTpi protein delivered into the substantia nigra (SN) of mice brains protected dopaminergic neuronal cell death in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD animal model. Our results indicate that the Tat-GSTpi protein inhibited cell death from MPP+- and MPTP-induced damage, suggesting that it plays a protective role during the loss of dopaminergic neurons in PD and that it could help to identify the mechanism responsible for neurodegenerative diseases, including PD.

Protective Effects of PEP-1-GSTA2 Protein in Hippocampal Neuronal Cell Damage Induced by Oxidative Stress.

Glutathione S-transferase alpha 2 (GSTA2), a member of the glutathione S-transferase family, plays the role of cellular detoxification against oxidative stress. Although oxidative stress is related to ischemic injury, the role of GSTA2 against ischemia has not been elucidated. Thus, we studied whether GSTA2 prevents ischemic injury by using the PEP-1-GSTA2 protein which has a cell-permeable protein transduction domain. We revealed that cell-permeable PEP-1-GSTA2 transduced into HT-22 cells and markedly protected cell death via the inhibition of reactive oxygen species (ROS) production and DNA damage induced by oxidative stress. Additionally, transduced PEP-1-GSTA2 promoted mitogen-activated protein kinase (MAPK), and nuclear factor-kappaB (NF-κB) activation. Furthermore, PEP-1-GSTA2 regulated Bcl-2, Bax, cleaved Caspase-3 and -9 expression protein levels. An in vivo ischemic animal model, PEP-1-GSTA2, markedly prevented the loss of hippocampal neurons and reduced the activation of microglia and astrocytes. These findings indicate that PEP-1-GSTA2 suppresses hippocampal cell death by regulating the MAPK and apoptotic signaling pathways. Therefore, we suggest that PEP-1-GSTA2 will help to develop the therapies for oxidative-stress-induced ischemic injury.

RADIOGRAPHIC MEASUREMENT OF VERTEBRAL HEART SCALE IN KOREAN WILD RACCOON DOGS (NYCTEREUTES PROCYONOIDES KOREENSIS).

Raccoon dogs (Nyctereutes procyonoides koreensis), which belong to the Canidae family, are the second most injured wildlife animals rescued by the Gangwon Wildlife Medical Rescue Center. Various imaging evaluation methods including echocardiography have been developed, but thoracic radiography remains essential for the diagnosis and management of heart disease in dogs. In particular, vertebral heart scale (VHS) measurement is usually used to evaluate the dimensions of the heart silhouette on thoracic radiographs and can measure cardiomegaly more objectively. The VHS of 50 raccoon dogs without cardiac diseases were measured using thoracic radiography in right lateral (RL) and ventrodorsal (VD) recumbent positions. The VHS in the RL view of 50 raccoon dogs was 9.03 ± 0.52 vertebrae (v), which was slightly smaller than the VHS measured in the VD view of 46 raccoon dogs (9.79 ± 0.84 v). In addition, the thoracic morphology of raccoon dogs was determined to be intermediate (thoracic depth-to-width ratio, 0.75-1.25), and thoracic morphology, gender, and weight were not significantly correlated with VHS. The VHS of raccoon dogs in this study will help veterinarians diagnose potential cardiac diseases in raccoon dogs.

Protective effect of GK2 fused BLVRA protein against oxidative stress-induced dopaminergic neuronal cell damage.

It is well known that oxidative stress is highly associated with Parkinson's disease (PD), and biliverdin reductase A (BLVRA) is known to have antioxidant properties against oxidative stress. In this study, we developed a novel N-acetylgalactosamine kinase (GK2) protein transduction domain (PTD) derived from adenosine A2A and fused with BLVRA to determine whether the GK2-BLVRA fusion protein could protect dopaminergic neuronal cells (SH-SY5Y) from oxidative stress in vitro and in vivo using a PD animal model. GK2-BLVRA was transduced into various cells, including SH-SY5Y cells, without cytotoxic effects, and this fusion protein protected SH-SY5Y cells and reduced reactive oxygen species production and DNA damage after 1-methyl-4-phenylpyridinium (MPP+ ) exposure. GK2-BLVRA suppressed mitogen-activated protein kinase (MAPK) activation and modulated apoptosis-related protein (Bcl-2, Bax, cleaved Caspase-3 and -9) expression levels. In the PD animal model, GK2-BLVRA transduced into the substantia nigra crossed the blood-brain barrier and markedly reduced dopaminergic neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animals. These results indicate that our novel PTD GK-2 is useful for the transduction of protein, and GK2-BLVRA exhibits a beneficial effect against dopaminergic neuronal cell death in vitro and in vivo, suggesting that BLVRA can be used as a therapeutic agent for PD.

Tat-Thioredoxin-like protein 1 attenuates ischemic brain injury by regulation of MAPKs and apoptosis signaling.

Thioredoxin-like protein 1 (TXNL1), one of the thioredoxin superfamily known as redox-regulator, plays an essential in maintaining cell survival via various antioxidant and anti-apoptotic mechanisms. It is well known that relationship between ischemia and oxidative stress, however, the role of TXNL1 protein in ischemic damage has not been fully investigated. In the present study, we aimed to determine the protective role of TXNL1 against on ischemic injury in vitro and in vivo using cell permeable Tat-TXNL1 fusion protein. Transduced Tat-TXNL1 inhibited ROS production and cell death in H2O2-exposed hippocampal neuronal (HT-22) cells and modulated MAPKs and Akt activation, and pro-apoptotic protein expression levels in the cells. In an ischemia animal model, Tat-TXNL1 markedly decreased hippocampal neuronal cell death and the activation of astrocytes and microglia. These findings indicate that cell permeable Tat-TXNL1 protects against oxidative stress in vitro and in vivo ischemic animal model. Therefore, we suggest Tat-TXNL1 can be a potential therapeutic protein for ischemic injury. [BMB Reports 2023; 56(4): 234-239].

Association between oral cavity cancer and metabolic syndrome.

PURPOSE: Few studies have been conducted on the association between oral cavity cancer and metabolic diseases. This study aimed to investigate the relationship between oral cavity cancer and metabolic diseases. METHODS: This cohort study used the database of the Korean National Health Insurance Service, which contains medical data of 97% of the Korean population. Oral cavity cancer occurred in a total of 2718 patients. Metabolic syndrome was defined according to IDF criteria. The Cox proportional hazard regression model was used. RESULTS: The HR for oral cavity cancer in patients with metabolic syndrome was 1.113(95% CI 1.006-1.232), which was significantly higher than that in normal patients, especially in males (p = 0.0386). When the number of metabolic syndrome factors was ≥ 3, the HR of oral cavity cancer was 1.191(95% CI 1.026-1.383), which was significantly higher than that of 0 metabolic syndrome factors, especially in males (p = 0.0218). When the number of metabolic syndrome factors was ≥ 3, the HR for oral cavity cancer was 1.439(95% CI 1.066-1.942), which was significantly higher than that of 0 metabolic syndrome factors, especially in males aged < 50 years (p = 0.0173). CONCLUSION: Metabolic syndrome increases the risk of oral cavity cancer only in males. In addition, the incidence of oral cavity cancer increased as the number of factors constituting metabolic syndrome increased, only in young males aged < 50 years. Thus, metabolic syndrome is an important risk factor for oral cavity cancer, particularly in young males.

Therapeutic Administration of Oxcarbazepine Saves Cerebellar Purkinje Cells from Ischemia and Reperfusion Injury Induced by Cardiac Arrest through Attenuation of Oxidative Stress.

Research reports using animal models of ischemic insults have demonstrated that oxcarbazepine (a carbamazepine analog: one of the anticonvulsant compounds) extends neuroprotective effects against cerebral or forebrain injury induced by ischemia and reperfusion. However, research on protective effects against ischemia and reperfusion cerebellar injury induced by cardiac arrest (CA) and the return of spontaneous circulation has been poor. Rats were assigned to four groups as follows: (Groups 1 and 2) sham asphyxial CA and vehicle- or oxcarbazepine-treated, and (Groups 3 and 4) CA and vehicle- or oxcarbazepine-treated. Vehicle (0.3% dimethyl sulfoxide/saline) or oxcarbazepine (200 mg/kg) was administered intravenously ten minutes after the return of spontaneous circulation. In this study, CA was induced by asphyxia using vecuronium bromide (2 mg/kg). We conducted immunohistochemistry for calbindin D-28kDa and Fluoro-Jade B histofluorescence to examine Purkinje cell death induced by CA. In addition, immunohistochemistry for 4-hydroxy-2-nonenal (4HNE) was carried out to investigate CA-induced oxidative stress, and immunohistochemistry for Cu, Zn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) was performed to examine changes in endogenous antioxidant enzymes. Oxcarbazepine treatment after CA significantly increased the survival rate and improved neurological deficit when compared with vehicle-treated rats with CA (survival rates ≥ 63.6 versus 6.5%), showing that oxcarbazepine treatment dramatically protected cerebellar Purkinje cells from ischemia and reperfusion injury induced by CA. The salvation of the Purkinje cells from ischemic injury by oxcarbazepine treatment paralleled a dramatic reduction in 4HNE (an end-product of lipid peroxidation) and increased or maintained the endogenous antioxidant enzymes (SOD1 and SOD2). In brief, this study shows that therapeutic treatment with oxcarbazepine after CA apparently saved cerebellar neurons (Purkinje cells) from CA-induced neuronal death by attenuating oxidative stress and suggests that oxcarbazepine can be utilized as a therapeutic medicine for ischemia and reperfusion brain (cerebellar) injury induced by CA.

The Impact of the COVID-19 Pandemic on Otitis Media.

Otitis media is one of the most common diseases in children, with 80% of children experiencing it by the age of three years. Therefore, the resulting social burden is enormous. In addition, many countries still suffer from complications due to otitis media. Meanwhile, COVID-19 has affected many diseases, with otitis media being one of the most strongly affected. This review aims to find out how COVID-19 has affected otitis media and its significance. A series of measures brought about by COVID-19, including emphasis on personal hygiene and social distancing, had many unexpected positive effects on otitis media. These can be broadly classified into four categories: first, the incidence of otitis media was drastically reduced. Second, antibiotic prescriptions for otitis media decreased. Third, the incidence of complications of otitis media was reduced. Fourth, the number of patients visiting the emergency room due to otitis media decreased. The quarantine measures put in place due to COVID-19 suppressed the onset and exacerbation of otitis media. This has great implications for the treatment and prevention of otitis media.

Protective Effects of Topical Administration of Laminarin in Oxazolone-Induced Atopic Dermatitis-like Skin Lesions.

Laminarin is a polysaccharide isolated from brown marine algae and has a wide range of bioactivities, including immunoregulatory and anti-inflammatory properties. However, the effects of laminarin on atopic dermatitis have not been demonstrated. This study investigated the potential effects of topical administration of laminarin using a Balb/c mouse model of oxazolone-induced atopic dermatitis-like skin lesions. Our results showed that topical administration of laminarin to the ear of the mice improved the severity of the dermatitis, including swelling. Histological analysis revealed that topical laminarin significantly decreased the thickening of the epidermis and dermis and the infiltration of mast cells in the skin lesion. Serum immunoglobulin E levels were also significantly decreased by topical laminarin. Additionally, topical laminarin significantly suppressed protein levels of oxazolone-induced proinflammatory cytokines, such as interleukin-1ß, tumor necrosis factor-α, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α in the skin lesion. These results indicate that topical administration of laminarin can alleviate oxazolone-induced atopic dermatitis by inhibiting hyperproduction of IgE, mast cell infiltration, and expressions of proinflammatory cytokines. Based on these findings, we propose that laminarin can be a useful candidate for the treatment of atopic dermatitis.

Metformin ameliorates olanzapine-induced obesity and glucose intolerance by regulating hypothalamic inflammation and microglial activation in female mice.

Olanzapine (OLZ), a widely used second-generation antipsychotic drug, is known to cause metabolic side effects, including diabetes and obesity. Interestingly, OLZ-induced metabolic side effects have been demonstrated to be more profound in females in human studies and animal models. Metformin (MET) is often used as a medication for the metabolic side effects of OLZ. However, the mechanisms underlying OLZ-induced metabolic disturbances and their treatment remain unclear. Recent evidence has suggested that hypothalamic inflammation is a key component of the pathophysiology of metabolic disorders. On this background, we conducted this study with the following three objectives: 1) to investigate whether OLZ can independently induce hypothalamic microgliosis; 2) to examine whether there are sex-dependent differences in OLZ-induced hypothalamic microgliosis; and 3) to examine whether MET affects hypothalamic microgliosis. We found that administration of OLZ for 5 days induced systemic glucose intolerance and hypothalamic microgliosis and inflammation. Of note, both hypothalamic microglial activation and systemic glucose intolerance were far more evident in female mice than in male mice. The administration of MET attenuated hypothalamic microglial activation and prevented OLZ-induced systemic glucose intolerance and hypothalamic leptin resistance. Minocycline, a tetracycline derivative that prevents microgliosis, showed similar results when centrally injected. Our findings reveal that OLZ induces metabolic disorders by causing hypothalamic inflammation and that this inflammation is alleviated by MET administration.

Flow pattern-dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells.

Endothelial mitochondria play a pivotal role in maintaining endothelial cell (EC) homeostasis through constantly altering their size, shape, and intracellular localization. Studies show that the disruption of the basal mitochondrial network in EC, forming excess fragmented mitochondria, implicates cardiovascular disease. However, cellular consequences underlying the morphological changes in the endothelial mitochondria under distinctively different, but physiologically occurring, flow patterns (i.e., unidirectional flow [UF] versus disturbed flow [DF]) are largely unknown. The purpose of this study was to investigate the effect of different flow patterns on mitochondrial morphology and its implications in EC phenotypes. We show that mitochondrial fragmentation is increased at DF-exposed vessel regions, where elongated mitochondria are predominant in the endothelium of UF-exposed regions. DF increased dynamin-related protein 1 (Drp1), mitochondrial reactive oxygen species (mtROS), hypoxia-inducible factor 1, glycolysis, and EC activation. Inhibition of Drp1 significantly attenuated these phenotypes. Carotid artery ligation and microfluidics experiments further validate that the significant induction of mitochondrial fragmentation was associated with EC activation in a Drp1-dependent manner. Contrarily, UF in vitro or voluntary exercise in vivo significantly decreased mitochondrial fragmentation and enhanced fatty acid uptake and OXPHOS. Our data suggest that flow patterns profoundly change mitochondrial fusion/fission events, and this change contributes to the determination of proinflammatory and metabolic states of ECs.