Diabetic encephalopathy is a major complication with cognitive impairment and neurodegeneration in patients with type 1 or type 2 diabetes mellitus (DM). DM-induced glucolipotoxicity is a risk factor for Alzheimer’s disease–like phenotype, including amyloidogenesis, tau hyperphosphorylation, and neuronal apoptosis. Although the detailed mechanism underlying the pathogenesis of diabetic encephalopathy remains unclear, mitochondrial oxidative stress is emerging as a key factor for diabetic complications and neurodegeneration. A deeper understanding of the regulatory mechanism of mitochondrial oxidative stress under hyperglycemic conditions will provide insights into the development of therapeutic strategies for diabetic encephalopathy. Here, we review the role of mitochondrial oxidative stress in diabetic encephalopathy and the regulatory mechanisms by which high glucose induces the generation of mitochondrial reactive species oxygen species in neuronal cells. This review also summarizes the mitochondrial-dependent and -independent pathways (O-linked-N-acetylglucosaminylation, calcium, and glycogen synthase kinase 3β signaling) that regulate mitochondrial oxidative stress in a DM model.

Ticks and tick-borne pathogens are among the main sources of interest in veterinary medicine and public health. This review aimed to cover published data on tick species and their geographical distribution in Korea. Over 143 articles regarding ticks were published between 1966 and 2022, and reporting at least 29 species belonging to the family Ixodidae and five belonging to the family Argasidae. Among these, Haemaphysalis longicornis, H. flava, and Ixodes nipponensis were the main genera distributed nationwide, whereas Amblyomma was mostly identified in the southern region. Conversely, only a limited number of Argasidae ticks were present, including the genera Argas and Ornithodoros. Considering the changes in tick distribution patterns due to global warming, continuous nationwide monitoring of ticks is required.

The ambiguity of complex regional pain syndrome (CRPS) posed a challenge to many medical researchers in the early days after its discovery and continues to do so till date. The establishment of the Budapest Criteria of the International Association for the Study of Pain resolved certain queries on CRPS. Many aspects of CRPS, such as pathophysiology and etiology, remain unknown. Therefore, of these aspects, we focused on the genetic basis of CRPS. In this qualitative review, we summarized the recent findings on the genetic association of CRPS and analyzed the roles of genes identified in each study and limitations of the studies. In particular, we confirmed the reliability of each study by comparing the following research, which used the following control groups or the same candidate genes. Notably, specific phenotypes of CRPS with dystonia indicate a significant association with human leukocyte antigen (HLA)-DQ8. Further, HLA-DQ8, which is associated with aberrant CD4+ T-cell reaction, could be associated with CRPS etiology since an increased CD4+ T-cell population was reported in CRPS patients. In addition, matrix metalloproteinase (MMP)-9 found in genome-wide expression profiling is noteworthy since MMP-9 is associated with neuro-inflammatory reactions. Despite these suggestions on the genetic aspects of CRPS, the pathophysiology and etiology of CRPS may be polygenic and multifactorial, influenced by multiple genes and other factors. Further, some studies have suggested that CRPS phenotypes have different etiologies. Thus, further studies with the precise classification of CRPS on a unified basis and with a significant number of case groups are required

Over the past decade, platelet-rich plasma (PRP) and platelet derivatives have been widely investigated in the field of regenerative medicine due to their high concentrations of platelet- related growth factors, cytokines, and other proteins. Recently, many clinical studies have suggested their regenerative therapeutic efficacy in treating several disorders in medical field. However, their therapeutic applications are not well characterized in veterinary medicine as in human and experimental animals. This article reviews functional roles of platelets, scientific concepts, and clinical use of PRP and platelet derivatives in veterinary medicine. It also presents guidelines for veterinary applications of PRP in the future.

Iron deficiency is known to be a common nutritional disorder in many countries, especially among children, women of childbearing age and pregnant women. SUNACTIVE Fe-P80 is a new type of iron supplement that applies nanotechnlateology for the purpose of overcoming the disadvantages of food supplements. This study was conducted to investigate the potential adverse effects of a 28-day repeated oral dose of SUNACTIVE Fe-P80 in rats. SUNACTIVE Fe-P80 was administered once daily by gavage to Sprague-Dawley rats for 28 days at doses of 0, 500, 1,000, and 2,000 mg/kg/day. Additional recovery groups from the control and highdose groups were observed for a 14-day recovery period. At the scheduled termination, the animals were sacrificed, their organs weighed, and blood samples collected. There were no treatment-related effects in the context of clinical signs, body weight, food intake, ophthalmoscopy, urinalysis, necropsy findings, organ weights, and hematologic, serum biochemical and histopathological parameters at any dose tested. Under the present experimental conditions, the no-observed-adverse-effect level of SUNACTIVE Fe-P80 was ≥ 2,000 mg/kg/day in both the sexes, and no target organs were identified. Thus, the results suggest that SUNACTIVE Fe-P80 is relatively safe, as no treatment-related adverse effects were observed following a 28-day repeated oral dose experiment.

Sirtuin 1 (SIRT1), the most conserved nicotinamide adenine dinucleotide-dependent protein deacetylase, is involved in the regulation of energy metabolism, genomic stability, and development. SIRT1 knockout (SIRT1) mice exhibit decreased energy expenditure and hypersensitivity to a high-fat diet (HFD). SIRT1 deficiency in the testis has also been shown to cause male infertility in animal models. Therefore, the present study was conducted to examine the alteration of the testicular function of SIRT1 mice on HFD. Six-week-old mice were fed ad libitum as wild type (WT) and SIRT1 male mice with either a control diet or with HFD for 32 weeks and then were sacrificed. The levels of biomarkers for hepatotoxicity, sex hormones, and cytokines were analyzed in the serum and blood-testis barrier, and the sperm morphology was examined in the testis and epididymal spermatozoa. Interestingly, an enlargement of seminal vesicles was observed in the SIRT1 mice fed with HFD. A significantly higher level of hepatotoxicity was also seen in these mice. The concentration of serum testosterone increased in HFD-fed SIRT1 mice compared to the controls. The levels of interleukin-1β and TNF-α increased in both HFD-fed WT and SIRT1 mice. In RT-PCR, the m RNA expression of tight junction protein 2 and claudin 3 significantly decreased in HFD-fed SIRT1 compared to those of the controls. Degenerative spermatocytes and spermatids were detected in the HFD-fed SIRT1 mice testicular section. Sperm motility decreased in WT and SIRT1 with HFD feeding, and sperm concentration decreased significantly in WT-HFD and SIRT1 mice with or without HFD feeding. Taken together, HFD can alter energy and steroid metabolism in SIRT1-deficient mice, which can lead to imbalances in motility and production of sperm and testosterone that can result in male reproductive disorders.

Radioiodine (131I) has been used for the treatment of feline hyperthyroidism since the 1990s in the USA and Europe, and it is recommended as the most effective treatment for feline hyperthyroidism because it has a high therapeutic effect, small side effects, and does not require anesthesia. In this study, the pharmacological properties of the Thyrokitty injection (I-131), which is being developed as a treatment for feline hyperthyroidism, using radioiodine (131I) as an active ingredient, was tested. The %cell uptake of the Thyrokitty injection (I-131) in FRTL- 5 thyroid cells was 0.410 ± 0.016%, which was about 18 times higher compared to Clone 9 hepatocytes, and it was decreased by 30.7% due to the competitive reaction with iodine (sodium iodide). In addition, the %cell growth of the FRTL-5 thyroid cells was reduced by 25.0% by treatment with the Thyrokitty injection (I-131). As a result of the tissue distribution test, the Thyrokitty injection (I-131) was distributed at the highest concentration at 0.083 hours (5 minutes) after subcutaneous administration to animals in most organs except the stomach, small intestine, large intestine, muscle and thyroid gland, and it was excreted mainly through the kidneys. The stomach and thyroid gland showed a typical distribution pattern observed when radioiodine (131I) was administered. In addition, about 78.45% of the total amount of excretion was excreted within 48 hours, of which more than 85% was excreted in urine. In conclusion, the Thyrokitty injection (I-131) has the same mechanism of action, potency, absorption, distribution, metabolism and excretion characteristics as radioiodine (131I) reported in connection with the treatment of feline hyperthyroidism. In the future, using the results of this study, it is expected that the Thyrokitty (I-131) could be safely used in the clinical treatment of feline hyperthyroidism.

Following the previous study, the toxicity of a single subcutaneous administration of the Thyrokitty injection (I-131) and the side effects that may occur at therapeutic doses were confirmed. The Thyrokitty injection (I-131) was administered subcutaneously once at a dose of 0, 2.0, 6.0, and 18.0 mCi/kg, 5 male and female rats per group, and mortality, general symptom observation, and weight measurement were performed for 2 weeks, followed by observation of autopsy findings. There were no deaths, and no statistically significant weight change was observed. Mild hair loss, fissures, and crusting were observed by general symptom observation, but it was not a toxic change related to the Thyrokitty injection (I-131). Gastric atrophy and a decrease in the size of the spleen were observed by the autopsy. As a results of single subcutaneous administration of the Thyrokitty Injection (I-131) to rats at a maximum dose of 18.0 mCi/kg, a decrease in the size of the spleen and gastric atrophy were observed as the dose of the Thyrokitty Injection (I-131) increased, which may be related to the test substance. No abnormal findings related to the Thyrokitty injection (I-131) were observed. Therefore, the approximate lethal dose of the Thyrokitty injection (I-131) was 18.0 mCi/kg or more. In addition, as reported for the treatment of feline hyperthyroidism with radioiodine (131I), side effects of the Thyrokitty injection (I-131) are expected to be extremely rare. Temporary dysphagia and fever may occur, but it will recover naturally. It should be administered with caution in cats with diseases such as urinary system, cardiovascular system, gastrointestinal system and endocrine system, especially with kidney disease. And it should not be used in cats who are pregnant, lactating, or likely. It is expected that the Thyrokitty injection (I-131) can be used for clinical treatment in Korea as a veterinary drug.

Global concerns have grown regarding emerging infectious diseases (EIDs) caused by previously unknown pathogens. Considering that strengthening surveillance capacity for unknown diseases is one of the core capacities for preparedness and early response to EIDs, identifying areas with poor capacity could be beneficial to prioritize regions for the improvement of surveillance. In this regard, we aimed to develop prediction models to identify high risk areas for low surveillance capacity for unknown diseases in a global scale. Unexplained death events reported between 2015 and 2019 were collected from two internet-based surveillance systems, ProMED-mail and Global Public Health Intelligence Network. From the reports, the number of reported unexplained deaths at the first report and the time gap between death and report were extracted as measures for sensitivity and timeliness of surveillance capacity, respectively. Using geographical locations of the reports and published global scale spatial data, including demographic, socioeconomic, public health and geographical variables, we fitted two boosted regression tree models to predict regions with the low sensitivity and timeliness. The performance of prediction model for the low sensitivity showed moderate validity, but in terms of the model for timeliness, the performance was unreliable. Therefore, we provided predicted risk only for low sensitivity. The mean predicted risks of low sensitivity were, respectively, 45.2%, 37.4%, 12.5%, and 3.0% in low-income, lower middle-income, upper middle-income, and high-income countries. Enhancing surveillance capacity in low-income countries is highly required, given the predicted low level of sensitivity despite the importance of early response.

This study aimed to identify prognostic factors and describe the treatment outcomes of multidrug therapy in dogs with meningoencephalomyelitis of unknown etiology (MUE). A total of 23 dogs diagnosed with MUE were treated with prednisolone in combination with cyclosporine, cytosine arabinoside (CA), leflunomide, and mycophenolate mofetil. Based on the survival time, these dogs were divided into two groups: group A (n = 10), surviving for < 100 days, and group B (n = 13), surviving for > 100 days. Signalment, seizure activity, cerebrospinal fluid (CSF) analysis results, and magnetic resonance (MR) imaging findings were reviewed. Survival studies were conducted to investigate the association of each prognostic factor and treatment with the clinical outcome. There were no significant differences in age, sex, body weight, occurrence of seizures, cell number and protein concentration in the CSF, or location of lesions between groups A and B. Abnormal MR features were more frequently observed in group A than in group B. It was identified that the longest median survival time was administration of multi-drug therapy including CA. In conclusion, abnormal MR features were associated with poor prognosis in dogs with MUE and CA-based multi-drug therapy could be considered the most effective treatment of MUE.

Repetitive or excessive exposure to ultraviolet (UV) radiation causes oxidative stress-mediated skin photoaging through the overproduction of reactive oxygen species. Actinidia polygama is known as a medical plant used in oriental medicine for treating several diseases such as abdominal pain, stroke and rheumatoid arthritis. Recently, it was reported that A. polygama extract had anti-wrinkle and skin hydrating properties in ultraviolet B (UVB)-exposed hairless mice. However, the molecular biological mechanism of this extract on alleviating skin photoaging is still unknown. Therefore, we investigated the anti-photoaging effects of PB203, which is the powder of A. polygama extract, in the in vivo and in vitro photoaging models. First, PB203 showed 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities due to the presence of anti-oxidant components including flavonoids and polyphenols. In UVB-irradiated hairless mice, oral administration of PB203 (100 mg/ kg) significantly improved wrinkle formation, skin dehydration, elasticity and skin barrier function by decreasing the levels of matrix metalloproteinases (MMPs) and increasing those of collagen I, filaggrin, involucrin and loricrin. Especially, the reduced production of p-p38, p-c-Jun and p-c-Fos by PB203 reversed the elevated levels of MMPs mediated by UVB exposure, resulting in the upregulation of collagen I expression. Consistent with these animal data, PB203 remarkably enhanced the mRNA expression of collagen I, filaggrin, involucrin and loricrin, while suppressed that of MMPs in UVB-irradiated HaCaT cells. And PB203 increased the wound recovery rate of cells by promoting their proliferation and migration. Moreover, PB203 significantly recovered the activity of superoxide dismutase inhibited by UVB in both mice and cells. In conclusion, PB203, which protects skin from UVB-induced photodamage by exerting antioxidant properties, can be considered to have sufficient potential as a functional ingredient or therapeutic agent improving skin photoaging and related skin symptoms.

The surfactant, 2-{2-[2-(4-nonylphenoxy)ethoxy]ethoxy}ethan-1-ol, is used in detergents, pesticides, cosmetics, and disinfectants. Since it is found in products that can be inhaled, we evaluated its toxicity to humans upon exposure. A total of 18 rats were exposed to nasal inhalation for 4 hr to determine the acute inhalation toxicity of 2-{2-[2-(4-nonylphenoxy) ethoxy]ethoxy}ethan-1-ol; the exposure concentrations were 5.0, 1.0, and 0.5 mg/L, with three males and three females at each concentration. After the end of the exposure, mortality, general symptoms, and weight changes were observed for 14 days, and autopsy findings were confirmed. The actual concentrations of the test substance in the chamber during the exposure were measured as 3.29, 1.03, and 0.52 mg/L, respectively. The delivered dose was 552.72, 173.04, and 87.36 mg/kg/day for males, and 829.08, 259.56, and 131.04 mg/kg/day for females. As a result of the test in the OECD Test Guideline 436, all animals exposed to a concentration of 3.29 mg/L died; three males and one female died out of six exposed to the 1.0 mg/L concentration. In addition, one died out of six males exposed to a 0.5 mg/L concentration. As a result, 2-{2-[2-(4-nonylphenoxy)ethoxy]ethoxy}ethan-1-ol was considered to be Globally Harmonized System of Classification and Labelling of Chemicals Category 2 (> 0.5–1 mg/L).