Efficacy of Trametinib in Alleviating Cisplatin-Induced Acute Kidney Injury: Inhibition of Inflammation, Oxidative Stress, and Tubular Cell Death in a Mouse Model.

Cisplatin, a platinum-based chemotherapeutic, is effective against various solid tumors, but its use is often limited by its nephrotoxic effects. This study evaluated the protective effects of trametinib, an FDA-approved selective inhibitor of mitogen-activated protein kinase kinase 1/2 (MEK1/2), against cisplatin-induced acute kidney injury (AKI) in mice. The experimental design included four groups, control, trametinib, cisplatin, and a combination of cisplatin and trametinib, each consisting of eight mice. Cisplatin was administered intraperitoneally at a dose of 20 mg/kg to induce kidney injury, while trametinib was administered via oral gavage at 3 mg/kg daily for three days. Assessments were conducted 72 h after cisplatin administration. Our results demonstrate that trametinib significantly reduces the phosphorylation of MEK1/2 and extracellular signal-regulated kinase 1/2 (ERK1/2), mitigated renal dysfunction, and ameliorated histopathological abnormalities. Additionally, trametinib significantly decreased macrophage infiltration and the expression of pro-inflammatory cytokines in the kidneys. It also lowered lipid peroxidation by-products, restored the reduced glutathione/oxidized glutathione ratio, and downregulated NADPH oxidase 4. Furthermore, trametinib significantly inhibited both apoptosis and necroptosis in the kidneys. In conclusion, our data underscore the potential of trametinib as a therapeutic agent for cisplatin-induced AKI, highlighting its role in reducing inflammation, oxidative stress, and tubular cell death.

Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from the bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, a higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to the reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating the acquisition of a rapid supply of ATP for proliferation in AML. Therefore, the targeting of mesothelin presents a potentially promising approach to mitigating the progression of AML through the inhibition of glycolysis and mitochondrial respiration in myeloid cells.

Bilateral epididymal tuberculosis causing abscess formation and male infertility: a case report and literature review.

Background: Epididymal tuberculosis (TB) is an uncommon form of TB, although it is known to develop frequently in the male reproductive system. Infertility is rare but important among subsequent possible complications caused by the disease, particularly in young males. Moreover, it is difficult to differentiate epididymal TB from other epididymo-testicular diseases. Herein, we report a rare case of a young patient recently diagnosed with bilateral epididymal TB causing male infertility. Case Description: We report the case of a 37-year-old patient who presented with left testicular pain and swelling lasting for about 8 months. He had no comorbidities, including pulmonary TB. Additionally, he had no children and was worried about infertility. Physical examination revealed a firm and tender mass, which was palpable in the left epididymal area, measuring 3.5 cm × 2.2 cm in diameter. Acid-fast bacilli staining and polymerase chain reaction of the urine were negative. Semen analysis showed no sperm in the semen, implying azoospermia diagnosis. Scrotal ultrasonography was suggestive of severe left epididymitis with abscess formation without abnormal appearance of the testicle. Due to persistent testicular pain, intermittent fever, and severe epididymitis with abscess formation, the patient underwent epididymectomy. Surgical exploration of the testicle revealed a severely swollen and firm epididymis with abscess materials and hard and dilated vas deferens connected to the epididymis, implying severe inflammatory reactions. The histopathological examination revealed chronic granulomatous inflammation with caseous necrosis in the epididymis tissue. According to histopathological results, the patient was treated with anti-TB pharmacological treatment. About 1 month after the surgery, he presented with pain in the right testicular area, implying bilateral TB epididymis. After completion of the pharmacological treatment, the patient had no complaints, such as pain or swelling in both testicular areas. Conclusions: Physicians should consider the possibility of epididymal TB in patients with persistent testicular symptoms for early diagnosis. When a definitive diagnosis of epididymal TB is established, or clinically suspected, immediate treatment initiation, including pharmacological and, if needed, surgical treatment, should be performed to prevent subsequent complications, including abscess formation or male infertility, particularly in young males.

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea.

BACKGROUND: Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study. METHODS: Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53. RESULTS: CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history. CONCLUSIONS: Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

[Radiologic Manifestations of Pulmonary Nuclear Protein in Testis Midline Carcinoma: A Case Report]. / 폐에 발생한 ê³ í™˜ 핵단백질 ì •ì¤‘ì„ ì•”ì˜ ì˜ìƒì˜í•™ì  소견: 증례 ë³´ê³ .

Nuclear portein in testis (NUT) midline carcinoma is a very rare and low-differentiating malignant epithelial tumor that differentiates very aggressively and has poor prognosis. NUT midline carcinoma occurring in the lungs in particular can be confused with other cancers because few cases have been reported in Korea to date and can show various histological forms. Reports of radiology findings are very rare worldwide. Here we report the imaging findings of pulmonary NUT midline carcinoma in a 25-year-old female along with pathological findings.

Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury.

Cisplatin is a chemotherapeutic agent widely used in the treatment of various cancers, but its application is often limited due to complications such as acute kidney injury (AKI). Orexins are hypothalamic neuropeptides that modulate the sleep-wake cycle, neuroendocrine function, and the autonomic nervous system. Emerging evidence suggests that orexin A (OXA) has anti-inflammatory and neuroprotective effects in animal models of neuroinflammatory diseases of the central nervous system. However, the effect of OXA on kidney diseases has not been examined. Here, we investigated whether OXA has a protective effect in a murine model of cisplatin-induced AKI. Intraperitoneal administration of OXA ameliorated renal dysfunction, and histological abnormalities in mice injected with cisplatin. OXA inhibited cisplatin-induced oxidative stress through the modulation of prooxidant and antioxidant enzymes. This peptide reduced apoptotic cell death by inhibiting the p53-mediated pathway in mice injected with cisplatin. OXA also alleviated cisplatin-induced cytokine production and macrophage infiltration into injured kidneys. Taken together, these results showed that OXA ameliorates cisplatin-induced AKI via antioxidant, anti-apoptotic, and anti-inflammatory actions. This peptide could be a potential therapeutic agent for cisplatin-induced AKI.

MSeg-Net: A Melanoma Mole Segmentation Network Using CornerNet and Fuzzy K-Means Clustering.

Melanoma is a dangerous form of skin cancer that results in the demise of patients at the developed stage. Researchers have attempted to develop automated systems for the timely recognition of this deadly disease. However, reliable and precise identification of melanoma moles is a tedious and complex activity as there exist huge differences in the mass, structure, and color of the skin lesions. Additionally, the incidence of noise, blurring, and chrominance changes in the suspected images further enhance the complexity of the detection procedure. In the proposed work, we try to overcome the limitations of the existing work by presenting a deep learning (DL) model. Descriptively, after accomplishing the preprocessing task, we have utilized an object detection approach named CornerNet model to detect melanoma lesions. Then the localized moles are passed as input to the fuzzy K-means (FLM) clustering approach to perform the segmentation task. To assess the segmentation power of the proposed approach, two standard databases named ISIC-2017 and ISIC-2018 are employed. Extensive experimentation has been conducted to demonstrate the robustness of the proposed approach through both numeric and pictorial results. The proposed approach is capable of detecting and segmenting the moles of arbitrary shapes and orientations. Furthermore, the presented work can tackle the presence of noise, blurring, and brightness variations as well. We have attained the segmentation accuracy values of 99.32% and 99.63% over the ISIC-2017 and ISIC-2018 databases correspondingly which clearly depicts the effectiveness of our model for the melanoma mole segmentation.

Taurine Supplementation Inhibits the Expression of Atrogin-1 and MURF-1, Protein Degradation Marker Genes, in Skeletal Muscle of C26-Induced Cachexia Mouse Model.

This study was designed to investigate the therapeutic effects of taurine in attenuating muscle atrophy. C26 carcinoma cells were cultured and injected into the scapulae of Balb/c mice with 1 × 106 cells. Taurine (200 µl suspension) was orally administered at the concentration of 200 mg/kg of body weight for 2 weeks. Femur muscle tissue, spleen, and gonadal fat tissue were collected and weighed. Muscle tissue was stained by H&E for histopathological analysis. The transcriptional expression of atrogin-1 and MuRF-1 gene was checked by real-time PCR. C26 cells, which induced tumor growth, caused a loss in muscle mass and gonadal fat tissue mass. Simultaneously, there was an increase in spleen and tumor tissue mass. In contrast, taurine supplementation showed a downregulatory effect on the transcriptional expression profile of muscle degradative factors atrogin-1 and MuRF-1. Our findings suggest that taurine has the potential to inhibit muscle atrophy and can be developed as a safe treatment option against muscle loss in sarcopenia patients.

Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice.

Septic acute kidney injury (AKI) is an important medical problem worldwide, but current treatments are limited. During sepsis, lipopolysaccharide (LPS) activates various signaling pathways involved in multiorgan failure. Carnosic acid is a natural phenolic diterpene and has multiple bioactivities, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, the effect of carnosic acid on septic AKI has not been explored. Therefore, this study aimed to determine whether carnosic acid has a therapeutic effect on LPS-induced kidney injury. Administration of carnosic acid after LPS injection ameliorated histological abnormalities and renal dysfunction. Cytokine production, immune cell infiltration, and nuclear factor-κB activation after LPS injection were also alleviated by carnosic acid. The compound suppressed oxidative stress with the modulation of pro-oxidant and antioxidant enzymes. Tubular cell apoptosis and caspase-3 activation were also inhibited by carnosic acid. These data suggest that carnosic acid ameliorates LPS-induced AKI via inhibition of inflammation, oxidative stress, and apoptosis and could serve as a useful treatment agent for septic AKI.

Effect of Process Control Parameters on the Filtration Performance of PAN-CTAB Nanofiber/Nanonet Web Combined with Meltblown Nonwoven.

Nanofibers have potential applications as filters for particles with diameters <10 µm owing to their large specific surface area, macropores, and controllable geometry or diameter. The filtration efficiency can be increased by creating nanonets (<50 nm) whose diameter is smaller than that of nanofibers. This study investigates the effect of process conditions on the generation of nanonet structures from a polyacrylonitrile (PAN) solution containing cation surfactants; in addition, the filtration performance is analyzed. The applied electrospinning voltage and the electrostatic treatment of meltblown polypropylene (used as a substrate) are the most influential process parameters of nanonet formation. Electrospun polyacrylonitrile-cetylmethylammonium bromide (PAN-CTAB) showed a nanofiber/nanonet structure and improved thermal and mechanical properties compared with those of the electrospun PAN. The pore size distribution and filter efficiency of the PAN nanofiber web and PAN-CTAB nanofiber/nanonet web with meltblown were measured. The resulting PAN-CTAB nanofiber/nanonet air filter showed a high filtration efficiency of 99% and a low pressure drop of 7.7 mmH2O at an air flow rate of 80 L/min. The process control methods for the nanonet structures studied herein provide a new approach for developing functional materials for air-filtration applications.

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms.

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the "Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm" to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury.

Sepsis is the major cause of acute kidney injury (AKI) in severely ill patients, but only limited therapeutic options are available. During sepsis, lipopolysaccharide (LPS), an endotoxin derived from bacteria, activates signaling cascades involved in inflammatory responses and tissue injury. Apamin is a component of bee venom and has been shown to exert antioxidative, antiapoptotic, and anti-inflammatory activities. However, the effect of apamin on LPS-induced AKI has not been elucidated. Here, we show that apamin treatment significantly ameliorated renal dysfunction and histological injury, especially tubular injury, in LPS-injected mice. Apamin also suppressed LPS-induced oxidative stress through modulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and heme oxygenase-1. Moreover, tubular cell apoptosis with caspase-3 activation in LPS-injected mice was significantly attenuated by apamin. Apamin also inhibited cytokine production and immune cell accumulation, suppressed toll-like receptor 4 pathway, and downregulated vascular adhesion molecules. Taken together, these results suggest that apamin ameliorates LPS-induced renal injury through inhibiting oxidative stress, apoptosis of tubular epithelial cells, and inflammation. Apamin might be a potential therapeutic option for septic AKI.

Washable Colorimetric Nanofiber Nonwoven for Ammonia Gas Detection.

The colorimetric sensor is a facile, cost-effective, and non-power-operated green energy material for gas detection. In this study, the colorimetric sensing property of a meta-aramid/dye 3 nanofiber sensor for ammonia (NH3) gas detection was investigated. This colorimetric sensor was prepared using various dye 3 concentrations via electrospinning. Morphological, thermal, structural, and mechanical analyses of the sensor were carried out by field-emission scanning electron microscopy, thermogravimetric analysis, Fourier-transform infrared spectroscopy, and a universal testing machine, respectively. A homemade computer color matching machine connected with a gas flow device characterized the response of the meta-aramid/dye 3 nanofiber colorimetric sensor to various exposure levels of NH3 gas. From the results, we confirmed that this colorimetric green energy sensor could detect ammonia gas in the concentration of 1-10 ppm with a sensing response time of 10 s at room temperature. After washing with laundry detergent for 30 min, the colorimetric sensors still exhibited sensing property and reversibility.

Anti-fibrotic effects of synthetic TGF-ß1 and Smad oligodeoxynucleotide on kidney fibrosis in vivo and in vitro through inhibition of both epithelial dedifferentiation and endothelial-mesenchymal transitions.

Kidney fibrosis is a common process of various kidney diseases leading to end-stage renal failure irrespective of etiology. Myofibroblasts are crucial mediators in kidney fibrosis through production of extracellular matrix (ECM), but their origin has not been clearly identified. Many study proposed that epithelial and endothelial cells become myofibroblasts by epithelial dedifferentiation and endothelial-mesenchymal transition (EndoMT). TGF-ß1/Smad signaling plays a crucial role in partly epithelial-mensencymal transition (EMT) and EndoMT. Thus, we designed the TGF-ß1/Smad oligodeoxynucleotide (ODN), a synthetic short DNA containing complementary sequence for Smad transcription factor and TGF-ß1 mRNA. Therefore, this study investigated the anti-fibrotic effect of synthetic TGF-ß1/Smad ODN on UUO-induced kidney fibrosis in vivo model and TGF-ß1-induced in vitro model. To examine the effect of TGF-ß1/Smad ODN, we performed various experiments to evaluate kidney fibrosis. The results showed that UUO induced inflammation, ECM accumulation, epithelial dedifferentiation and EndoMT processes, and tubular atrophy. However, synthetic TGF-ß1/Smad ODN significantly suppressed UUO-induced fibrosis. Furthermore, synthetic ODN attenuated TGF-ß1-induced epithelial dedifferentiation and EndoMT program via blocking TGF-ß1/Smad signaling. In conclusion, this study demonstrated that administration of synthetic TGF-ß1/Smad ODN attenuates kidney fibrosis, epithelial dedifferentiation, and EndoMT processes. The findings propose the possibility of synthetic ODN as a new effective therapeutic tool for kidney fibrosis.

Protective Effects of Melatonin Against Aristolochic Acid-Induced Nephropathy in Mice.

Melatonin, a pineal hormone, is well known to regulate the sleep-wake cycle. Besides, the hormone has been shown to display pleiotropic effects arising from its powerful anti-oxidant and anti-inflammatory activities. Recent studies have reported that melatonin exerts protective effects in animal models of kidney disease. However, the potential effects of melatonin on aristolochic acid (AA)-induced nephropathy (AAN) have not yet been investigated. Here, we found that the administration of melatonin ameliorated AA-induced renal dysfunction, as evidenced by decreased plasma levels of blood urea nitrogen and creatinine and histopathological abnormalities such as tubular dilatation and cast formation. The upregulation of tubular injury markers after AA injection was reversed by melatonin. Melatonin also suppressed AA-induced oxidative stress, as evidenced by the downregulation of 4-hydroxynonenal and reduced level of malondialdehyde, and modulated expression of pro-oxidant and antioxidant enzymes. In addition, p53-dependent apoptosis of tubular epithelial cells, infiltration of macrophages and CD4+ T cells into damaged kidneys, and renal expression of cytokines and chemokines were inhibited by melatonin. Moreover, melatonin attenuated AA-induced tubulointerstitial fibrosis through suppression of the tumor growth factor-ß/Smad signaling pathway. These results suggest that melatonin might be a potential therapeutic agent for AAN.

Melatonin Inhibits Transforming Growth Factor-ß1-Induced Epithelial-Mesenchymal Transition in AML12 Hepatocytes.

Recent studies showed that melatonin, a well-known pineal hormone that modulates the circadian rhythm, exerts beneficial effects against liver fibrosis. However, mechanisms for its protective action against the fibrotic processes remain incompletely understood. Here, we aimed to explore the effects of the hormone on transforming growth factor-ß1 (TGF-ß1)-stimulated epithelial-mesenchymal transition (EMT) in AML12 hepatocytes. Pretreatment with melatonin dose-dependently reversed downregulation of an epithelial marker and upregulation of mesenchymal markers after TGF-ß1 stimulation. Additionally, melatonin dose-dependently suppressed an increased phosphorylation of Smad2/3 after TGF-ß1 treatment. Besides the canonical Smad signaling pathway, an increase in phosphorylation of extracellular signal-regulated kinase 1/2 and p38 was also dose-dependently attenuated by melatonin. The suppressive effect of the hormone on EMT stimulated by TGF-ß1 was not affected by luzindole, an antagonist of melatonin membrane receptors, suggesting that its membrane receptors are not required for the inhibitory action of melatonin. Moreover, melatonin suppressed elevation of intracellular reactive oxygen species (ROS) levels in TGF-ß1-treated cells. Finally, TGF-ß1-stimulated EMT was also inhibited by the antioxidant N-acetylcysteine. Collectively, these results suggest that melatonin prevents TGF-ß1-stimulated EMT through suppression of Smad and mitogen-activated protein kinase signaling cascades by deactivating ROS-dependent mechanisms in a membrane receptor-independent manner.

Sarcomatoid carcinoma after radiotherapy for early-stage oral squamous cell carcinoma: Case report.

RATIONALE: Sarcomatoid carcinoma is a rare variant of squamous cell carcinoma (SCC) with poor prognosis. Previous radiation has been reported as one of the etiologic factors. PATIENT CONCERNS: We describe a case of a 57-year-old man presented with a painless mass in the left supraclavicular area. Five years before, he was diagnosed with SCC in floor of mouth (FOM) and underwent radiotherapy (RT). DIAGNOSES: Sonography-guided biopsy on the supraclavicular lymph node revealed diffuse spindle cell proliferation with a focus of squamous differentiation. Local recurrence on primary site or distant metastasis was not obvious on both computed tomography (CT) of the neck and F-fluorodeoxyglucose positron emission tomography CT. The final diagnosis was confirmed as sarcomatoid carcinoma via surgery. INTERVENTIONS: The patient underwent surgery including explorative resection of the mouth floor, excision of the submandibular gland, and modified radical neck dissection. Following surgery, the patient received adjuvant radiation therapy. OUTCOMES: There were no complications according to the surgery. Six months after adjuvant therapy, distant metastasis to liver was identified. The patient is currently undergoing palliative chemotherapy. LESSONS: This may be the first reported case of sarcomatoid carcinoma arising from early-stage SCC in FOM that was previously treated with RT alone. When RT is performed as a single modality for oral SCC, even in an early stage, rigorous follow-up should be performed.

Bee venom attenuates Porphyromonas gingivalis and RANKL-induced bone resorption with osteoclastogenic differentiation.

Porphyromonas gingivalis (P. gingivalis) is one of the major periodontal pathogens leading to inflammation and alveolar bone resorption. Bone resorption is induced by osteoclasts, which are multinucleated giant cells. Osteoclastic bone resorption is mediated by enhanced receptor activator of nuclear factor-kappa B ligand (RANKL) signaling. Therefore, the down-regulation of RANKL downstream signals is regarded as an effective therapeutic target in the treatment of bone loss-associated disorders. The aim of this study was to evaluate whether purified bee venom (BV) could attenuate P. gingivalis-induced inflammatory periodontitis and RANKL-induced osteoclast differentiation. Inflammatory periodontitis induced by P. gingivalis increased alveolar bone resorption and increased expression of TNF-α and IL-1ß, while BV treatment resulted in decreased bone loss and pro-inflammatory cytokines. Similarly, RANKL-induced multinucleated osteoclast differentiation and osteoclast-specific gene expression, such as nuclear factor of activated T cells 1 (NFATc1), cathepsin K, tartrate-resistant acid phosphatase (TRAP), and integrin αvß3 were significantly suppressed by treatment with BV. We show that BV reduces P. gingivalis-induced inflammatory bone loss-related periodontitis in vivo and RANKL-induced osteoclast differentiation, activation, and function in vitro. These results suggest that BV exerts positive effects on inflammatory periodontitis associated osteoclastogenesis.

Therapeutic effects of bee venom on experimental atopic dermatitis.

Atopic dermatitis (AD) is a chronic skin inflammatory disease characterized by recurrent eczema and itching. It is caused by a poorly controlled immune response and damage to the skin barrier. Purified bee venom (BV) is a natural toxin produced by honeybees (Apis mellifera L.), and is well known for its anti­inflammatory, analgesic and anti­cancer effects against various types of disease. However, treatment strategies based on anti­inflammatory properties have not been adequately studied in AD. Thus, the present study examined the progression of AD­like skin lesions induced by ovalbumin (OVA) and the mechanism of action of BV. BV, administered by intraperitoneal inoculation, was observed to reduce the symptoms of AD, in addition to the serum immunoglobulin E levels, according to dorsal skin thickness and histopathologic analysis. The treatment also inhibited the infiltration of eosinophils and mast cells. These results suggested that it is possible to develop novel AD alternative therapy using BV by effectively suppressing allergic skin inflammation in AD.

Antifibrotic Effect of Smad Decoy Oligodeoxynucleotide in a CCl4-Induced Hepatic Fibrosis Animal Model.

Hepatic fibrosis is the wound-healing process of chronic hepatic disease that leads to the end-stage of hepatocellular carcinoma and demolition of hepatic structures. Epithelial⁻mesenchymal transition (EMT) has been identified to phenotypic conversion of the epithelium to mesenchymal phenotype that occurred during fibrosis. Smad decoy oligodeoxynucleotide (ODN) is a synthetic DNA fragment containing a complementary sequence of Smad transcription factor. Thus, this study evaluated the antifibrotic effects of Smad decoy ODN on carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. As shown in histological results, CCl4 treatment triggered hepatic fibrosis and increased Smad expression. On the contrary, Smad decoy ODN administration suppressed fibrogenesis and EMT process. The expression of Smad signaling and EMT-associated protein was markedly decreased in Smad decoy ODN-treated mice compared with CCl4-injured mice. In conclusion, these data indicate the practicability of Smad decoy ODN administration for preventing hepatic fibrosis and EMT processes.