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Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%–25% of patients with diabetes experience neuropathic pain, referred to as “painful DPN.” Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.

Background: Screening and treating healthcare workers (HCWs) for latent tuberculosis infection (LTBI) are essential for tuberculosis (TB) infection control. Adverse drug reactions (ADRs) to anti-TB drugs present challenges to patient safety and treatment completion. Objective: This study investigated the association between human leukocyte antigen (HLA) alleles and the risk of ADRs, especially drug hypersensitivity (DHS) and hepatotoxicity, in HCWs with LTBI receiving isoniazid (INH) and rifampin (RIF) therapy. Methods: Korean HCWs with LTBI who received a 3 month INH and RIF regimen were included in this study. HLA genotyping was performed on HCWs who experienced ADRs during treatment, as well as the control group consisted of individuals who did not develop ADRs. Results: Of the 67 patients, 29 (43.2%) experienced ADRs during INH and RIF therapy. The HLA-A*11:01 allele was more frequent in patients with DHS without hepatotoxicity (DSH+/H−) compared to the control group (DHS−/H−) (4/9, 44.4% vs. 3/38, 7.9%; odd ratio [OR], 8.554; 95% confidence interval [CI], 1.415–59.869; p = 0.018). Conversely, HLA-DPB1*05:01 was associated with an increased risk of hepatotoxicity regardless of DHS (10/20, 50% vs. 5/38, 13.2%; OR, 5.323; 95% CI, 1.493–21.518; p = 0.011). In the DHS with hepatotoxicity group (DHS+/H+), HLA-DPB1*05:01 was present in a higher proportion (3/5, 60% vs. 5/38, 13.2%; OR, 8.912; 95% CI, 1.110–92.993; p = 0.037), whereas HLA-A*11:01 was not observed in this group. Conclusions: The HLA-A*11:01 allele was associated with an increased risk of DHS without hepatotoxicity, whereas the HLA-DPB1*05:01 allele was associated with an increased risk of hepatotoxicity.

Because there is a shortage of donor kidneys, researchers are exploring the possibility of using genetically modified pig kidneys for transplantation. Approaches involving knockout of carbohydrate genes or knockin of protective proteins have been attempted to determine the best gene modifications. In this study, we utilized GalT −/− ; hCD39;hCD55 and GalT −/− ; hCD39;hCD46;hCD55;thrombomodulin (TBM) pigs for transplantation in nonhuman primates (NHPs). The NHPs survived for 4 weeks after kidney transplantation (4 WAT) from the GalT −/− ; hCD39;hCD55 pig and for 6 WAT from the GalT −/− ; hCD39;hCD46;hCD55;TBM pig. However, messenger RNA (mRNA) sequencing and immunohistochemistry analysis revealed that the 6 WAT kidney exhibited more severe apoptosis, inflammation, loss of renal function, and renal fibrosis than the 4 WAT kidney. These results indicate that additional knockin of complement regulator ( hCD46 ) and coagulation regulator ( TBM ) is not enough to prevent renal damage, suggesting that improved immune suppression is needed for more prolonged survival.

The role of the gastric mucosal microbiome in Helicobacter pylori-negative gastric cancer (GC) remains unclear. Therefore, we aimed to characterize the microbial alterations and host inflammatory cytokine responses in H. pylori-negative GC. Gastric mucosal samples were obtained from 137 H. pylori-negative patients with GC (n = 45) and controls (chronic gastritis or intestinal metaplasia, n = 92). We performed 16S rRNA gene sequencing (n = 67), a quantitative reverse transcription-polymerase chain reaction to determine the relative mRNA expression levels of TNF (tumor necrosis factor), IL1B (interleukin 1 beta), IL6 (interleukin 6), CXCL8 (C-X-C motif chemokine ligand 8), IL10 (interleukin 10), IL17A (interleukin 17A), TGFB1 (transforming growth factor beta 1) (n = 113), and the correlation analysis between sequencing and expression data (n = 47). Gastric mucosal microbiota in patients with GC showed reduced diversity and a significantly different composition compared to that of the controls. Lacticaseibacillus was significantly enriched, while Haemophilus and Campylobacter were depleted in the cancer group compared to the control group. These taxa could distinguish the two groups in a random forest algorithm. Moreover, the combined relative abundance of these taxa, a GC microbiome index, significantly correlated with gastric mucosal IL1B expression, which was elevated in the cancer group. Overall, altered gastric mucosal microbiota was found to be associated with increased mucosal IL1B expression in H. pylori-negative GC.

Objective To explore the mechanism that macrophages promote epithelial-mesenchymal transformation (EMT) in bladder cancer cells. Methods A total of 137 tissues of bladder cancer (BC) were collected from Department of Urological Oncology of Chongqing University Cancer Hospital between 2000 and 2015. Immunohistochemical (IHC) assay was used to detect the expression of CLDN10 in 137 bladder cancer specimens, and statistical analysis was used to investigate the association in CLDN10 expression and clinical features. In mouse RAW264.7 macrophages and bladder cancer MB49 cells, siRNA technology was used to knockdown the expression of TNF-α in RAW264.7 cells. Western blot assay was performed to detect the levels of related protein expression of EMT in MB49 cells, while immunofluorescence assay was used to detect the combination of CLDN10 and β-catenin. Plate clone formation assay was performed to detect the levels of related protein expression of EMT in MB49 cells and RAW264.7 cells. Results In 137 samples, the proportion of overexpression of CLDN10 was 49.6% (68/137). Overexpression of CLDN10 was positively correlated with tumor(P=0.014) and lymphatic metastasis (P=0.005), and was negatively correlated with survival time(P=0.048) and recurrence-free survival (P=0.008). Treatment of exogenous TNF-α led to accumulation of CLDN10 in BC cell nucleus. The results of Western blotting showed the levels of EMT related proteins Vimentin, Snail and Twist were up-regulated(P < 0.05). Adversely, repression of TNF-α in macrophages resulted in decrease of the levels of EMT related proteins, Vimentin, Snail and Twist (P < 0.05). The levels of expression of Vimentin, snail and Twist were increased while the level of E-cadherin was decreased(P < 0.05) in MB49 cells after co-culturing of RAW264.7 cells and MB49 cells. Conclusion Macrophages can modulate BC cell proliferation and EMT progression by secreting TNF-α to regulate CLDN10/β-catenin mediated signaling pathway.

Osteoarthritis is a chronic inflammatory disease, and, due to the lack of fundamental treatment, the main objective is to alleviate pain and prevent cartilage damage. Kalopanax pictus Nakai and Achyranthes japonica Nakai are herbal plants known for their excellent anti-inflammatory properties. The objective of this study is to confirm the potential of a mixture extract of Kalopanax pictus Nakai and Achyranthes japonica Nakai as a functional raw material for improving osteoarthritis through anti-inflammatory effects in macrophages and MIA-induced arthritis experimental animals. In macrophages inflamed by lipopolysaccharide (LPS), treatment of Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture inhibits NF-κB and mitogen-activated protein kinase (MAPK) activities, thereby inhibiting inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), inflammatory factors PGE2, MMP-2, and MMP-9, and nitric oxide (NO) was reduced. In addition, in an animal model of arthritis induced by MIA (monosodium iodoacetate), administration of Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture reduced blood levels of inflammatory cytokines TNF-α and IL-6, inflammatory factors prostaglandin E2(PGE2), matrix metalloproteinase-2(MMP-2), and NO. Through these anti-inflammatory effects, MIA-induced pain reduction (recovery of clinical index, increase in weight bearing, and increase in area and width of the foot), recovery of meniscus damage, loss of cartilage tissue or inflammatory cells in tissue infiltration reduction, and recovery of the proteglycan layer were confirmed. Therefore, it is considered that Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture has the potential as a functional raw material that promotes joint health.

Abstract This study investigated the anti-obesity effects of yuja pomace extract fermented with lactic acid bacteria in rats with high-fat diet-induced obesity over a period of eight weeks. Epididymal fat cell size was significantly smaller, by about 33%, in the treatment groups given yuja pomace extract fermented with lactic acid bacteria compared to the CON group. Electron microscopic observation of hepatocyte microstructure showed that the number of lipid droplets was lower in hepatocytes, the number of mitochondria was higher, along with distinct cristae, and the rough endoplasmic reticula were well developed with stacks of cisternae and ribosomes. Thus, it is believed that yuja pomace extract fermented with lactic acid bacteria, by influencing body weight and lipid accumulation, is effective in the prevention and treatment of obesity.

Background : The association between body mass index (BMI) and mortality in patients with type 1 diabetes mellitus (T1DM) has been poorly examined and has never been systematically reviewed. This meta-analysis investigated the all-cause mortality risk for each BMI category among patients with T1DM. Methods : A systematic literature review of the PubMed, Embase, and Cochrane Library databases was performed in July 2022. Cohort studies comparing the mortality risk between BMI categories among patients with T1DM were eligible. Pooled hazard ratios (HRs) for all-cause mortality among underweight (BMI

Titanium dioxide (TiO₂) is a widely studied material with many attractive properties such as its photocatalytic features. However, its commercial use is limited due to issues such as deactivation in the visible spectrum caused by its wide bandgap and the short lifetime of photo-excited charge carriers. To overcome these challenges, various modifications could be considered. In this study, we investigated copper doping and electron beam treatment. As-spun TiO2 nanofibers were fabricated by electrospinning a TiO2 sol, which obtained viscosity through a polyvinylpyrrolidone (PVP) matrix. Cu-doped TiO2 nanofibers with varying dopant concentrations were synthesized by adding copper salts. Then, the as-spun nanofibers were calcined for crystallization. To evaluate photocatalytic performance, a photodegradation test of methylene blue aqueous solution was performed for 6 h. Methylene blue concentration was measured over time using UV-Vis spectroscopy. The results showed that Cu doping at an appropriate concentration and electron-beam irradiation showed improved photocatalytic efficiency compared to bare TiO2 nanofibers. When the molar ratio of Cu/Ti was 0.05%, photodegradation rate was highest, which was 10.39% higher than that of bare TiO2. As a result of additional electron-beam treatment of this sample, photocatalytic efficiency improved up to 8.93% compared to samples without electron-beam treatment.

Purpose Despite the high incidence of epilepsy during adolescence, little attention has been paid to the outcomes and prognosis of adolescent-onset epilepsy. The aim of this study was to investigate the long-term pharmacological and psychosocial outcomes of adolescent-onset epilepsy. Methods From 1993 to 2019, the electronic medical records of adolescent-onset epilepsy patients were retrieved from Asan Medical Center Children’s Hospital. Seizure outcomes were evaluated based on the seizure-free period at last contact. Possible predictors of remission, relapse, and intractability were investigated. Neuropsychiatric comorbidities, socioeconomic status, and transition outcomes were also assessed. Results In total, 137 patients were enrolled in this study. The median age at diagnosis of epilepsy was 14 years and the mean duration of therapy was 13.0 years. During follow-up, 93 patients (67.9%) achieved terminal remission, of which 27 cases (19.7%) resolved. Relapse after withdrawal of medication occurred in 74 patients (54.0%), and the presence of electroencephalographic abnormalities (odds ratio [OR], 8.23; 95% confidence interval [CI], 1.39 to 48.87; P=0.020), poor adherence (OR, 4.84; 95% CI, 2.13 to 11.02; P=0.000), and history of febrile seizures (OR, 4.10; 95% CI, 1.21 to 13.93; P=0.024) were risk factors for relapse. Neurodevelopmental and psychological comorbidities were documented in 17 (12.4%) and 12 (8.8%) patients, respectively. Thirty-six (26.3%) patients transferred to adult clinics, at a mean age of 21.9 years. Conclusion This study showed overall favorable seizure outcomes with a high rate of remission, but with frequent relapse after withdrawal.

Nicotinamide phosphoribosyl transferase (NAMPT) is a critical regulator of cellular nicotinamide adenine dinucleotide (NAD)+ levels. Here, the authors show that blood NAMPT contributes to the circadian rhythm generation of locomotor activity and energy expenditure by regulating hypothalamic NAD+ levels.

Monitoring of cytokine storm markers is critical for determining the disease progression and treatment efficacy. In this study, we developed a novel fourplex electrochemical (EC) biosensor using nanohole array (NHA) structures containing several nanoholes on a single electrode for detecting cytokines with a low limit. A framework was developed for fabricating and optimizing multiplexed EC sandwich immunoassays using NHA electrodes because an NHA can enhance the EC detection of molecular binding by controlling the binding sites of captured biomolecules. For detecting multiple cytokines, the captured antibodies were immobilized on the surface-modified NHA and sandwich immunoassays with amperometric signal amplifications using poly-streptavidin horseradish peroxidase conjugates and 3,3′,5,5′-tetramethylbenzidine. Under the optimal conditions, the EC NHA immunosensors exhibited high sensitivity and specificity with a limit of detection of 1 pg/mL and a detection range of 1–300 pg/mL. The results revealed that the developed NHA sensor exhibits reliable EC characteristics and could be used to analyze multiple cytokines using small sample volume and subsequently developed for other applications.