Unveiling the Dual Threat: How Microbial Infections and Healthcare Deficiencies Fuel Cervical and Prostate Cancer Deaths in Africa.

Cervical and prostate cancer account for 7.1 and 7.3 deaths per 100,000 people globally in 2022. These rates increased significantly to 17.6 and 17.3 in Africa, respectively, making them the second and third leading cause of cancer deaths in Africa, only surpassed by breast cancer. The human papillomavirus is the prime risk factor for cervical cancer infection. On the other hand, prostate cancer risks include ageing, genetics, race, geography, and family history. However, these factors alone cannot account for the high mortality rate in Africa, which is more than twice the global mortality rate for the two cancers. We searched PubMed, Embase, Scopus, and Web of Science to select relevant articles using keywords related to microorganisms involved in cervical and prostate cancer and the impact of poor healthcare systems on the mortality rates of these two cancers in Africa by carrying out a detailed synopsis of the studies on microbial agents involved and the contributory factors to the deteriorating healthcare system in Africa. It became apparent that the developed countries come first in terms of the prevalence of cervical and prostate cancer. However, more people per capita in Africa die from these cancers as compared to other continents. Also, microbial infections (bacterial or viral), especially sexually transmitted infections, cause inflammation, which triggers the pathogenesis and progression of these cancers among the African population; this has been linked to the region's deficient health infrastructure, making it difficult for people with microbial infections to access healthcare and hence making infection control and prevention challenging. Taken together, untreated microbial infections, primarily sexually transmitted infections due to the deficient healthcare systems in Africa, are responsible for the high mortality rate of cervical and prostate cancer.

Biomarkers to Predict Multiorgan Distress Syndrome and Acute Kidney Injury in Critically Ill Surgical Patients.

Background and Objectives: Critically ill surgical patients are susceptible to various postoperative complications, including acute kidney injury (AKI) and multiorgan distress syndrome (MODS). These complications intensify patient suffering and significantly increase morbidity and mortality rates. This study aimed to identify the biomarkers for predicting AKI and MODS in critically ill surgical patients. Materials and Methods: We prospectively enrolled critically ill surgical patients admitted to the intensive care unit via the emergency department between July 2022 and July 2023. A total of 83 patients were recruited, and their data were used to analyze MODS. Three patients who showed decreased creatinine clearance at the initial presentation were excluded from the analysis for AKI. Patient characteristics and laboratory parameters including white blood cell (WBC) count, neutrophil count, delta neutrophil index, urine and serum ß2-microglobulin, and urine serum mitochondrial DNA copy number (mtDNAcn) were analyzed to determine the reliable biomarker to predict AKI and MODS. Results: The following parameters were independently correlated with MODS: systolic blood pressure (SBP), initial neutrophil count, and platelet count, according to a logistic regression model. The optimal cut-off values for SBP, initial neutrophil count, and platelet count were 113 mmHg (sensitivity 66.7%; specificity 73.9%), 8.65 (X3) (109/L) (sensitivity 72.2%; specificity 64.6%), and 195.0 (X3) (109/L) (sensitivity 66.7%; specificity 81.5%), respectively. According to the logistic regression model, diastolic blood pressure (DBP) and initial urine mtDNAcn were independently correlated with AKI. The optimal cut-off value for DBP and initial urine mtDNAcn were 68.5 mmHg (sensitivity 61.1%; specificity 79.5%) and 1225.6 copies/µL (sensitivity 55.6%; specificity 95.5%), respectively. Conclusions: SBP, initial neutrophil count, and platelet count were independent predictors of MODS in critically ill patients undergoing surgery. DBP and initial urine mtDNAcn levels were independent predictors of AKI in critically ill surgical patients. Large-scale multicenter prospective studies are needed to confirm our results.

Expression of Immune-Related and Inflammatory Markers and Their Prognostic Impact in Colorectal Cancer Patients.

The tumor microenvironment of colorectal cancer (CRC) is heterogenous; thus, it is likely that multiple immune-related and inflammatory markers are simultaneously expressed in the tumor. The aim of this study was to identify immune-related and inflammatory markers expressed in freshly frozen CRC tissues and to investigate whether they are related to the clinicopathological features and prognosis of CRC. Seventy patients with CRC who underwent curative surgical resection between December 2014 and January 2017 were included in this study. Tissue samples were obtained from tumor and non-tumor areas in the patients' colons. The concentrations of immune-related markers (APRIL/TNFSF13, BAFF, LAG-3, PD-1, PD-L1, and CTLA-4) and inflammatory markers (CHIT, MMP-3, osteocalcin, pentraxin-3, sTNF-R1, and sTNF-R2) in the samples were measured using the Bio-plex Multiplex Immunoassay system. The concentrations of APRIL/TNFSF13, BAFF, and MMP-3 in the samples were significantly high; thus, we conducted analyses based on the cut-off values for these three markers. The high-APRIL/TNFSH13-expression group showed a significantly higher rate of metastatic lesions than the low-expression group, whereas the high-MMP-3-expression group had higher CEA levels, more lymph node metastases, and more advanced disease stages than the low-expression group. The five-year disease-free survival of the high-MMP-3-expression group was significantly shorter than that of the low-expression group (65.1% vs. 90.2%, p = 0.033). This study provides evidence that the APRIL/TNFSF13, BAFF, and MMP-3 pathway is overexpressed in CRC tissues and is associated with unfavorable clinicopathological features and poor prognosis in CRC patients. These markers could serve as diagnostic or prognostic biomarkers for CRC.

Effects of Hydrogen Gas Inhalation on Community-Dwelling Adults of Various Ages: A Single-Arm, Open-Label, Prospective Clinical Trial.

Molecular hydrogen (H2) is a versatile therapeutic agent. H2 gas inhalation is reportedly safe and has a positive impact on a range of illnesses, including Alzheimer's disease (AD). Herein, we investigated the effects of 4 weeks of H2 gas inhalation on community-dwelling adults of various ages. Fifty-four participants, including those who dropped out (5%), were screened and enrolled. The selected participants were treated as a single group without randomization. We evaluated the association between total and differential white blood cell (WBC) counts and AD risk at individual levels after 4 weeks of H2 gas inhalation treatment. The total and differential WBC counts were not adversely affected after H2 gas inhalation, indicating that it was safe and well tolerated. Investigation of oxidative stress markers such as reactive oxygen species and nitric oxide showed that their levels decreased post-treatment. Furthermore, evaluation of dementia-related biomarkers, such as beta-site APP cleaving enzyme 1 (BACE-1), amyloid beta (Aß), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor A (VEGF-A), T-tau, monocyte chemotactic protein-1 (MCP-1), and inflammatory cytokines (interleukin-6), showed that their cognitive condition significantly improved after treatment, in most cases. Collectively, our results indicate that H2 gas inhalation may be a good candidate for improving AD with cognitive dysfunction in community-dwelling adults of different ages.

Redox-Mechanisms of Molecular Hydrogen Promote Healthful Longevity.

Age-related diseases represent the largest threat to public health. Aging is a degenerative, systemic, multifactorial and progressive process, coupled with progressive loss of function and eventually leading to high mortality rates. Excessive levels of both pro- and anti-oxidant species qualify as oxidative stress (OS) and result in damage to molecules and cells. OS plays a crucial role in the development of age-related diseases. In fact, damage due to oxidation depends strongly on the inherited or acquired defects of the redox-mediated enzymes. Molecular hydrogen (H2) has recently been reported to function as an anti-oxidant and anti-inflammatory agent for the treatment of several oxidative stress and aging-related diseases, including Alzheimer's, Parkinson's, cancer and osteoporosis. Additionally, H2 promotes healthy aging, increases the number of good germs in the intestine that produce more intestinal hydrogen and reduces oxidative stress through its anti-oxidant and anti-inflammatory activities. This review focuses on the therapeutic role of H2 in the treatment of neurological diseases. This review manuscript would be useful in knowing the role of H2 in the redox mechanisms for promoting healthful longevity.

Roles and correlations of TIM-3 and LAG-3 with cytokines and chemokines in alcoholic liver disease.

BACKGROUND: Dysregulation of immune checkpoint regulators has been reported in alcoholic liver disease (ALD). This study was designed to assess the serum levels of cytokines and chemokines associated with ALD and uncover the possible disease correlations with the soluble TIM-3 and LAG-3. METHODS: The soluble TIM-3 and LAG-3 levels were measured by enzyme-linked immunoassay, and 14 cytokines and chemokines were measured using Luminex-based multiplex assay in 111 male ALD patients and 45 healthy controls (HCs). RESULTS: Our results showed that soluble TIM-3 was significantly increased (p < 0.001) while soluble LAG-3 was significantly decreased (p < 0.001) in ALD group compared to HCs. Among the 14 cytokines and chemokines assessed, granulocyte-colony stimulating factor (G-CSF) (p = 0.003) and interferon γ-induced protein (IP)-10 (p < 0.001) were significantly increased, while interleukin (IL)-4 (p = 0.005) and IL-12 (p40) (p = 0.001) were significantly decreased in the ALD group. Kaplan-Meier analysis showed that overall survival decreased in higher TIM-3 level individuals. CONCLUSIONS: Our results showed that TIM-3, LAG-3, and IP-10 appear to be important for clinical diagnosis of ALD and ALD severity and may represent potential therapeutic targets in ALD.

Effects of Personal Low-Frequency Stimulation Device on Myalgia: A Randomized Controlled Trial.

Electrotherapy is commonly used for myalgia alleviation. Low-frequency stimulation (LFS) is primarily used for controlling acute and chronic pain and is a non-invasive therapy that can be easily performed with electric stimulation applied on the skin. However, little evidence exists regarding the pain alleviation effects of personal low-frequency stimulation device for home use. Moreover, no studies have compared myalgia alleviation effects between personal low-frequency stimulation (PLS) and physical therapy (PT), which are most commonly used for patients with myalgia in hospitals and clinics. Therefore, we aimed to investigate the pain alleviation effects of PLS in patients with myalgia and compare these effects with those of conventional PT (transcutaneous electrical nerve stimulation + ultrasound). In total, 39 patients with myalgia in the neck, shoulder, back, and waist areas were randomly assigned to the personal low-frequency stimulation group (PLSG: n = 20) and physical therapy group (PTG: n = 19). Both groups were treated for 3 weeks (20 min per session and 5 sessions per week). Patients were assessed for pain intensity by surface electromyography (sEMG), visual analogue scale (VAS) and a short-form McGill pain questionnaire (SF-MPQ) before and after the intervention period. Our results showed that PLSG showed a tendency of muscle relaxation with a significant decrease in sEMG in the neck (p = 0.0425), shoulder (p = 0.0425), and back (p = 0.0046) areas compared to the control group. However, there was no significant difference in waist area. Additionally, VAS scores significantly decreased between pre- and post-treatment in both PTG (p = 0.0098), and PLSG (p = 0.0304) groups, but there was no significance difference between the groups. With respect to SF-MPQ, the PLSG showed greater pain alleviation (5.23 ± 0.25) effects than the PTG (6.23 ± 0.25). Accordingly, our results suggest that PLS treatment using a home device might offer positive assistance in pain alleviation for patients with myalgia that is as equally effective as conventional PT treatment. However, further detailed studies are required considering larger samples to fully claim the effectiveness of this device.

Characteristics of immune checkpoint regulators and potential role of soluble TIM-3 and LAG-3 in male patients with alcohol-associated liver disease.

The involvement of immune checkpoint regulators (ICs) in alcohol-associated liver diseases (ALDs) is still largely unknown. Here, we analyzed the levels of 16 soluble ICs (sICs) in male patients with ALD to determine their clinical significance. The 16 sICs were measured using a luminex-based multiplex assay in 115 patients with ALD and 47 healthy controls (HCs). The expressions of membrane-type (m) PD-1 and mCTLA-4 on CD4+ and CD8+ T lymphocytes and NK cells of 28 patients with ALD and 8 HCs were also measured. Correlation test and risk assessment were also conducted to evaluate biomarkers of ALD in clinical practice. Our results show that four sICs were upregulated (sCTLA-4, sTIM-3, sCD27, and sGITR) and two sICs were downregulated (sLAG-3 and sHVEM) in ALD. mPD-1 expression was significantly more greatly increased on CD4+T lymphocytes in the ALD group than in the HC group (p = 0.009). sTIM-3 was positively correlated, while sLAG-3 was negatively correlated with non-invasive liver fibrosis markers (AST/ALT, APRI, GPR, and FIB-4) and Maddrey discriminant function score. Risk factor analysis showed that sTIM-3 was consistently associated with ALD severity in both MDF and FIB-4 scores, and sLAG-3 was associated with FIB-4 scores. This study revealed the involvement of sCTLA-4, sTIM-3, sCD27, sGITRL, sLAG-3, and sHVEM in discriminating male patients with ALD. Expressions of sTIM-3 and sLAG-3 were correlated with liver fibrosis markers and significantly associated with ALD severity, which can be further studied as diagnostic markers and therapeutic targets in ALD.

Positive Impact on Public Perception toward Commune Health Stations (CHSs) in Rural Areas of Tyuen Quang Province, Vietnam, Following the Application of the Development Program for the Capacity-Building of CHSs.

This study aims to discover whether or not the capacity-building intervention through implementing the "Rural Area Development Program" in Tuyen Quang province, in partnership with the Korea International Cooperation Agency (KOICA) and the Vietnamese Department of Health", would positively affect the perception of the public toward the communal health stations (CHSs). To address this, three specific indicator-related satisfaction levels were examined regarding the infrastructure, the professional skills, and the service attitude of the medical personnel of the three CHSs toward outpatients. This cross-sectional study was conducted with 100 participants from three rural CHSs (Binh Yen, Vinh Loi, and Thang Long Communes). As a researcher-directed survey, a structured questionnaire was adopted to gauge the outpatient satisfaction levels in relation to the three indicators from the CHS medical milieu toward the patients and the medical services received. Descriptive and inferential analyses were performed to determine the perceptions of outpatient satisfaction relating to the three indicators. A higher satisfaction rate was found (overall 89-100% descriptive data with three indicators, as well as significant satisfaction differences in inferential data based on F-ratio and p-value) between the three regions with the three indicators, and two major data showed that the commune with a higher or more significant satisfaction rate or difference was Binh Yan > Vinh Loi > Thang Long. Collectively, this study clearly indicates the positive impact of CHSs capacity-building by implementing the Development Program in Tuyen Quang province with KOICA in relation to the public perception toward CHSs through significantly increased satisfaction levels-specifically, the infrastructure, the professional skills, and the service attitude of the medical milieu from the three CHSs toward outpatients.

Therapeutic Effects of Hydrogen Gas Inhalation on Trimethyltin-Induced Neurotoxicity and Cognitive Impairment in the C57BL/6 Mice Model.

Oxidative stress (OS) is one of the causative factors in the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease (AD) and cognitive dysfunction. In the present study, we investigated the effects of hydrogen (H2) gas inhalation in trimethyltin (TMT)-induced neurotoxicity and cognitive dysfunction in the C57BL/6 mice. First, mice were divided into the following groups: mice without TMT injection (NC), TMT-only injection group (TMT only), TMT injection + lithium chloride-treated group as a positive control (PC), and TMT injection + 2% H2 inhalation-treated group (H2). The TMT injection groups were administered a single dosage of intraperitoneal TMT injection (2.6 mg/kg body weight) and the H2 group was treated with 2% H2 for 30 min once a day for four weeks. Additionally, a behavioral test was performed with Y-maze to test the cognitive abilities of the mice. Furthermore, multiple OS- and AD-related biomarkers such as reactive oxygen species (ROS), nitric oxide (NO), calcium (Ca2+), malondialdehyde (MDA), glutathione peroxidase (GPx), catalase, inflammatory cytokines, apolipoprotein E (Apo-E), amyloid ß (Aß)-40, phospho-tau (p-tau), Bcl-2, and Bcl-2- associated X (Bax) were investigated in the blood and brain. Our results demonstrated that TMT exposure alters seizure and spatial recognition memory. However, after H2 treatment, memory deficits were ameliorated. H2 treatment also decreased AD-related biomarkers, such as Apo-E, Aß-40, p-tau, and Bax and OS markers such as ROS, NO, Ca2+, and MDA in both serum and brain. In contrast, catalase and GPx activities were significantly increased in the TMT-only group and decreased after H2 gas treatment in serum and brain. In addition, inflammatory cytokines such as granulocyte colony-stimulating factors (G-CSF), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) were found to be significantly decreased after H2 treatment in both serum and brain lysates. In contrast, Bcl-2 and vascular endothelial growth factor (VEGF) expression levels were found to be enhanced after H2 treatment. Taken together, our results demonstrated that 2% H2 gas inhalation in TMT-treated mice exhibits memory enhancing activity and decreases the AD, OS, and inflammatory-related markers. Therefore, H2 might be a candidate for repairing neurodegenerative diseases with cognitive dysfunction. However, further mechanistic studies are needed to fully clarify the effects of H2 inhalation on TMT-induced neurotoxicity and cognitive dysfunction.

Antioxidant Properties of Hydrogen Gas Attenuates Oxidative Stress in Airway Epithelial Cells.

Oxidative stress plays a crucial role in the development of airway diseases. Recently, hydrogen (H2) gas has been explored for its antioxidant properties. This study investigated the role of H2 gas in oxidative stress-induced alveolar and bronchial airway injury, where A549 and NCI-H292 cells were stimulated with hydrogen peroxide (H2O2) and lipopolysaccharide (LPS) in vitro. Results show that time-dependent administration of 2% H2 gas recovered the cells from oxidative stress. Various indicators including reactive oxygen species (ROS), nitric oxide (NO), antioxidant enzymes (catalase, glutathione peroxidase), intracellular calcium, and mitogen-activated protein kinase (MAPK) signaling pathway were examined to analyze the redox profile. The viability of A549 and NCI-H292 cells and the activity of antioxidant enzymes were reduced following induction by H2O2 and LPS but were later recovered using H2 gas. Additionally, the levels of oxidative stress markers, including ROS and NO, were elevated upon induction but were attenuated after treatment with H2 gas. Furthermore, H2 gas suppressed oxidative stress-induced MAPK activation and maintained calcium homeostasis. This study suggests that H2 gas can rescue airway epithelial cells from H2O2 and LPS-induced oxidative stress and may be a potential intervention for airway diseases.

Therapeutic Potential of Natural Products in Treating Neurodegenerative Disorders and Their Future Prospects and Challenges.

Natural products derived from plants, as well as their bioactive compounds, have been extensively studied in recent years for their therapeutic potential in a variety of neurodegenerative diseases (NDs), including Alzheimer's (AD), Huntington's (HD), and Parkinson's (PD) disease. These diseases are characterized by progressive dysfunction and loss of neuronal structure and function. There has been little progress in designing efficient treatments, despite impressive breakthroughs in our understanding of NDs. In the prevention and therapy of NDs, the use of natural products may provide great potential opportunities; however, many clinical issues have emerged regarding their use, primarily based on the lack of scientific support or proof of their effectiveness and patient safety. Since neurodegeneration is associated with a myriad of pathological processes, targeting multi-mechanisms of action and neuroprotection approaches that include preventing cell death and restoring the function of damaged neurons should be employed. In the treatment of NDs, including AD and PD, natural products have emerged as potential neuroprotective agents. This current review will highlight the therapeutic potential of numerous natural products and their bioactive compounds thatexert neuroprotective effects on the pathologies of NDs.

Mechanical Changes of the Lumbar Intervertebral Space and Lordotic Angle Caused by Posterior-to-Anterior Traction Using a Spinal Thermal Massage Device in Healthy People.

BACKGROUND: The axial (horizontal) traction approach has been traditionally used for treatment of low back pain-related spinal disorders such as nuclear protrusion, primary posterolateral root pain, and lower thoracic disc herniation; however, it is known to have some technical limitations due to reductions of the spinal curve. Lumbar lordosis plays a pivotal function in maintaining sagittal balance. Recently, vertical traction and combination traction have been attracting attention due to improving therapeutic outcomes, although evidence of their clinical application is rare; therefore, this study was conducted to investigate the mechanical changes of lumbar intervertebral space, lordotic angle, and the central spinal canal area through vertical traction treatment using a spinal massage device in healthy participants. METHODS: In total, 10 healthy subjects with no musculoskeletal disorders and no physical activity restrictions participated. The participants lay on the experimental device (CGM MB-1901) in supine extended posture and vertical traction force was applied in a posterior-to-anterior direction on the L3-4 and L4-5 lumbar sections at level 1 (baseline) and level 9 (traction mode). Magnetic resonance (MR) images were recorded directly under traction mode using the MRI scanner. The height values of the intervertebral space (anterior, center, and posterior parts) and lordosis angle of the L3-4 and L4-5 sections were measured using Image J software and the central spinal canal area (L4-5) was observed through superimposition method using the MR images. All measurement and image analyses were conducted by 2 experienced radiologists under a single-blinded method. RESULTS: The average height values of the intervertebral space under traction mode were significantly increased in both L3-4 and L4-5 sections compared to baseline, particularly in the anterior and central parts but not in the posterior part. Cobb's angle also showed significant increases in both L3-4 and L4-5 sections compared to baseline (p < 0.001). The central spinal canal area showed a slightly expanded feature in traction mode. CONCLUSIONS: In this pilot experiment, posterior-to-anterior vertical traction on L3-4 and L4-5 sections using a spinal massage device caused positive and significant changes based on increases of the intervertebral space height, lumbar lordosis angle, and central spinal canal area compared to the baseline condition. Our results are expected to be useful as underlying data for the clinical application of vertical traction.

Soluble type immune checkpoint regulators using multiplex luminex immunoassay in chronic hepatitis B patients.

AIMS: Soluble immune checkpoint regulators (sICs) were reported to have clinical impact on the diagnosis and progress of various diseases. This study compared the serum levels of 16 sICs in patients with chronic hepatitis B (CHB) to elucidate their clinical significance. METHODS: The sICs of 86 patients with CHB and 50 healthy controls (HCs) were measured using luminex-based multiplex assay. The sICs were correlated with laboratory markers and sIC levels were compared in cirrhotic and non-cirrhotic groups. RESULTS: The levels of soluble programmed death-ligand 1, soluble cluster of differentiation 80/B7-1 (sCD80/B7-1), soluble cluster of differentiation 86/B7-2, soluble B-lymphocyte and T-lymphocyte attenuator, soluble herpes virus entry mediator, soluble cluster 28, soluble cluster of differentiation 40, soluble glucocorticoid-induced TNFR-related protein, soluble ligand for receptor TNFRSF18/AITR/GITR, soluble Toll-like receptor 2 and soluble inducible T-cell costimulator (sICOS) were decreased, while soluble T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3) was increased in patients with CHB. Soluble programmed cell death protein 1 and sTIM-3 both positively correlated with hepatitis B virus (HBV) DNA level and increased in entecavir or tenofovir used group. The sTIM-3 positively correlated with aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase and gamma-glutamyl transferase to platelet ratio and fibrosis-4. Soluble cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) decreased in the liver cirrhosis (LC) group compared with the non-LC group. sCD80/B7-1 decreased LC risk, while soluble lymphocyte-activation gene increased LC risk by logistic regression analysis. CONCLUSIONS: Our results showed the preliminary data on dysregulated sICs in patients with CHB that may have clinical significance in diagnosis of patients with CHB. It can be applied to develop therapeutic target of HBV infection.

Effects of mineral complex material treatment on 2,4- dinitrochlorobenzene-induced atopic dermatitis like-skin lesions in mice model.

BACKGROUND: Atopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox disturbances, and pruritus. Prolonged topical treatment with medications such as corticosteroids, calcineurin inhibitors, and T-cell inhibitors may have some potential side-effects. To this end, many researchers have explored numerous alternative therapies using natural products and mineral compounds with antioxidant or immunomodulatory effects to minimize toxicity and adverse-effects. In the current study, we investigated the effects of mineral complex material (MCM) treatment on 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice. METHODS: Animals were divided into four groups; normal control (NC), negative control treated with DNCB only (DNCB only), positive control treated with DNCB and tacrolimus ointment (PC) and experimental group treated with DNCB and MCM patch (MCM). Skin inflammation and lesion severity were investigated through analyses of skin parameters (barrier score and strength, moisture and trans-epidermal water loss level), histopathology, immunoglobulin E, and cytokines. In addition, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT) levels were measured in both serum and skin lysate. RESULTS: Our results demonstrates that MCM patch improved the progression of AD-like skin lesions by significantly increasing skin barrier strength and decreasing trans-epidermal water loss. Additionally, dermal administration of MCM patch significantly reduced epidermal thickness, ROS, and NO levels in skin lysate. Furthermore, we found that MCM suppressed the levels of AD-involved (Th1 and Th2) cytokines such as IL-2, IFN-γ, and IL-4 in blood. In addition, the levels of other Th1, and Th2 and inflammatory cytokines such as IL-1ß, TNF-α, IL-6, IL-12(p70) and IL-10 were found lowest in the MCM group than in the DNCB only and PC groups. Moreover, we found total serum IgE level significantly increased after DNCB treatment, but decreased in the PC and MCM groups. CONCLUSION: Taken together, our findings suggest that MCM application may have beneficial effects either systemic or regional on DNCB-induced AD lesional skin via regulation of the skin barrier function and immune-redox response.

Role of Molecular Hydrogen in Skin Diseases and its Impact in Beauty.

In today's society, healthy skin and a beautiful appearance are considered the foundation of general well-being. The skin is the largest organ of the body and plays an important role in protecting it against various hazards such as environmental, physical, chemical, and biological hazards. These factors include mediators that lead to oxidation reactions that produce reactive oxygen/nitrogen species and additional oxidants in the skin cells. An increase in oxidants beyond the antioxidant capacity of its defense system causes oxidative stress and chronic inflammation in the body. This response can cause further disruption of collagen fibers and hinder the functioning of skin cells that may result in the development of various skin diseases including psoriasis, atopic dermatitis, and aging. In this review, we summarized the present information related to the role of oxidative stress in the pathogenesis of dermatological disorders, and its impact on physical beauty and the daily lives of patients. We also discussed how molecular hydrogen exhibits a therapeutic effect against skin diseases via its effects on oxidative stress. Furthermore, findings from this summary review indicate that molecular hydrogen might be an effective treatment modality for the prevention and treatment of skin-related illnesses.

Ameliorating effect of CpG-ODN (oligodeoxynucleotide) against radiation-induced lung injury in mice.

While radiation-induced lung injury (RILI) is known to be progressed by Th2 skewed, pro-inflammatory immune response, there have been few therapeutic attempts through Th1 immune modulation. We investigated whether the immunostimulant CpG-oligodeoxynucleotide (CpG-ODN) would be effective against RILI by way of measuring reactive oxygen species (ROS) and nitric oxides (NO), histopathology, micro-three-dimensional computer tomography (CT), and cytokine profiling. We found that KSK CpG-ODN (K-CpG) significantly reduced histopathological fibrosis when compared to the positive control (PC) group (p < 0.01). The levels of ROS production in serum and splenocyte of PC group were significantly higher than that of K-CpG group (p < 0.01). The production of nitric oxide (NO) in CpG-ODNs group was higher than that of PC group. Last, cytokine profiling illustrated that the protein concentrations of Th1-type cytokines such as IL-12 and TNF-α as well as Th2-type cytokine IL-5 in K-CpG group inclined to be significantly (p < 0.001 or p < 0.01) higher than those of in PC group. Collectively, our study clearly indicates that K-CpG is effective against RILI in mice by modulating the innate immune response. To our knowledge, this is the first note on anti-RILI effect of human type, K-CpG, clinically implying the potential of immunotherapy for RILI control.

Effects of Strong Acidic Electrolyzed Water in Wound Healing via Inflammatory and Oxidative Stress Response.

Strong acidic electrolyzed water (StAEW) is known to inactivate microorganisms but is not fully explored in the medical field. This study is aimed at exploring StAEW as a potential wound care agent and its mechanism. StAEW (pH: 2.65, ORP: 1159 mV, ACC: 32.1 ppm) was sprayed three times a day to the cutaneous wounds of hairless mice for seven days. Wound morphological and histological features and immune-redox markers were compared with saline- (Sal-) and alcohol- (Alc-) treated groups. Results showed that the StAEW group showed a significantly higher wound healing percentage than the Sal group on days 2, 4, 5, and 6 and the Alc group on day 4. The StAEW group also showed earlier mediation on proinflammatory cytokines such as tumor necrosis factor-α, interleukin- (IL-) 6, IL-1ß, and keratinocyte chemoattractant. In addition, basic fibroblast growth factor and platelet-derived growth factor were found to be significantly changed in favor of the fibroblast synthesis and angiogenesis. In line, the StAEW group showed a controlled amount of ROS and significantly decreased compared to the Alc group. The StAEW group also favored oxidative stress balance through antioxidant responses. Additionally, matrix metalloproteinases (MMP) 9 and MMP1 were also modulated for keratinocyte and cell migration. Taken together, this study has proven the wound healing effect of StAEW and its earlier mediation through oxidative and inflammatory responses.

Molecular hydrogen may enhance the production of testosterone hormone in male infertility through hormone signal modulation and redox balance.

Since the discovery of molecular hydrogen (H2) as a selective scavenger of free radicals like reactive oxygen species (ROS) and reactive nitrogen species (RNS), numerous studies have proved the potential application of H2 in therapeutic and preventative medicine. Moreover, H2 can regulate the intracellular signal as a signal modulator. However, it is still unclear in cell signaling involved in testosterone hormone production. Male fertility depends on the intra-testicular testosterone concentration, which is produced by the Leydig cell in the seminiferous tubules in testes. Although moderate amounts of ROS are needed for normal sperm function, the higher amounts might decrease testosterone production. High ROS decreases testosterone hormone production by dysregulation of hormonal signal from the hypothalamus to the Leydig cell as a result of redox imbalance. Lower level of testosterone fails to support the Leydig cell for the progression of spermatogenesis. Superoxide anion (O2-), hydroxyl radical (OH) and peroxynitrite (ONOO-) could also attack the DNA, lipid and protein, disrupting sperm structure and function and aggravating the milieu of male fertility and spermatogenesis. H2 regulates intracellular MAPK downstream cAMP signal and Ca2+ signal as a signal modulator to antagonize ROS signaling. Thus H2 can play a role in modulating signals involved in testosterone hormone production to improve male fertility caused by redox imbalance. We therefore hypothesize that molecular hydrogen may enhance testosterone production via cellular redox balance. By this hypothesis, we anticipate that molecular hydrogen may be an effective remedy in male infertility.

Hydrogen Water Drinking Exerts Antifatigue Effects in Chronic Forced Swimming Mice via Antioxidative and Anti-Inflammatory Activities.

PURPOSE: This study was performed to evaluate antifatigue effect of hydrogen water (HW) drinking in chronic forced exercise mice model. MATERIALS AND METHODS: Twelve-week-old C57BL6 female mice were divided into nonstressed normal control (NC) group and stressed group: (purified water/PW-treated group and HW-treated group). Stressed groups were supplied with PW and HW, respectively, ad libitum and forced to swim for the stress induction every day for 4 consecutive weeks. Gross antifatigue effects of HW were assessed by swimming endurance capacity (once weekly for 4 wk), metabolic activities, and immune-redox activities. Metabolic activities such as blood glucose, lactate, glycogen, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) as well as immune-redox activities such as reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), catalase, and the related cytokines were evaluated to elucidate underlying mechanism. Blood glucose and lactate were measured at 0 wk (before swimming) and 4 wk (after swimming). RESULTS: HW group showed a higher swimming endurance capacity (p < 0.001) than NC and PW groups. Positive metabolic effects in HW group were revealed by the significant reduction of blood glucose, lactate, and BUN in serum after 4 wk (p < 0.01, resp.), as well as the significant increase of liver glycogen (p < 0.001) and serum LDH (p < 0.05) than PW group. In parallel, redox balance was represented by lower NO in serum (p < 0.01) and increased level of GPx in both serum and liver (p < 0.05) than PW group. In line, the decreased levels of serum TNF-α (p < 0.01), IL-6, IL-17, and liver IL-1ß (p < 0.05) in HW group revealed positive cytokine profile compared to PW and NC group. CONCLUSION: This study shows antifatigue effects of HW drinking in chronic forced swimming mice via metabolic coordination and immune-redox balance. In that context, drinking HW could be applied to the alternative and safety fluid remedy for chronic fatigue control.