• Clinical and Experimental Reproductive Medicine
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• v.51 no.1
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• pp.28-41
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• 2024

Objective: Chronic scrotal hyperthermia (SHT) can lead to serious disorders of the male reproductive system, with oxidative stress playing a key role in the onset of these dysfunctions. Thus, we evaluated the impact of caffeine, a potent antioxidant, on cellular and tissue disorders in mice with chronic SHT. Methods: In this experimental study, 56 adult male NMRI mice were allocated into seven equal groups. Apart from the non-treated control group, all were exposed to heat stress. Two groups, termed "preventive" and "curative," were orally administered caffeine. The preventive mice began receiving caffeine immediately prior to heat exposure, while for the curative group, a caffeine regimen was initiated 15 consecutive days following cessation of heat exposure. Each treated group was subdivided based on pairing with a positive control (Pre/ curative [Cur]+PC) or a vehicle (Pre/Cur+vehicle). Upon conclusion of the study, we assessed sperm characteristics, testosterone levels, stereological parameters, apoptosis, antioxidant and oxidant levels, and molecular markers. Results: Sperm parameters, testosterone levels, stereological parameters, biochemical factors (excluding malondialdehyde [MDA]), and c-kit gene expression were significantly elevated in the preventive and curative groups, especially the former, relative to the other groups. Conversely, expression levels of the heat shock protein 72 (HSP72) and nuclear factor kappa beta (NF-κβ) genes, MDA levels, and apoptotic cell density were markedly lower in both caffeine-treated groups relative to the other groups, with more pronounced differences observed in the preventive group. Conclusion: Overall, caffeine attenuated cellular and molecular abnormalities induced by heat stress in the testis, particularly in the mice treated under the preventive condition.

• Anatomy and Cell Biology
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• v.56 no.4
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• pp.518-525
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• 2023

Septin4 belong to a family of polymerizing GTP-binding proteins that are required for many cellular functions, such as membrane compartmentalization, vesicular trafficking, mitosis, and cytoskeletal remodeling. Since, Septin4 is expressed specifically in the testis, we aimed to determine the association between Septin4 gene expression with sperm quality, DNA damage, and stress oxidative level in infertile patients. The present study included 60 semen samples that grouped into three groups: normozoospermia (n=20), asthenozoospermia (n=20), astheno-teratozoospermia (n=20). Initially, semen parameters were analyzed by using the World Health Organization protocol. The mRNA expression of Septin4 in sperm was examined using reverse transcription-polymerase chain reaction. Oxidative stress markers, i.e., total antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde, were determined by ELISA kit. The current study showed a statistically significant highly positive correlation in Septin4 gene expression with sperm motility, normal morphology, viability, capacity, and sperm mitochondrial membrane potential (MMP). However, it showed significant negative correlation with sperm DNA fragmentation. Septin4 had a significant correlation with stress oxidative factor and antioxidant enzyme levels. In conclusion, Septin4 gene expression provides clinical useful information for the diagnosis of male infertility. It might be a marker for discrimination between fertile and infertile patients. The current study showed a statistically significant highly positive correlation in Septin4 gene expression with sperm motility, normal morphology, viability, capacity, and sperm MMP. However, it shows significant negative correlation with sperm DNA fragmentation. Septin4 had a significant correlation with stress oxidative factor and antioxidant enzyme levels.

• Journal of Oral Medicine and Pain
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• v.48 no.4
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• pp.152-158
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• 2023

Purpose: This pilot study aimed to evaluate changes in joint space (JS) using cone-beam computed tomography (CBCT) images of patients diagnosed with temporomandibular joint (TMJ) osteoarthritis (OA) and to determine the association between occlusal changes and JS. Methods: CBCT images were used to measure the anterior, superior, and posterior JSs of the sagittal plane. The differences in JS values over time and between groups were compared. The percentage change in the anteroposterior position of the mandibular condyle between groups was also analyzed. Results: Thirty-four subjects (mean age=43.91±20.13), comprising eight males (23.5%) and 26 females (76.5%), were divided into 18 patients with no change in occlusion (NCO) and 16 patients with a change in occlusion (CO) during TMJ OA. The JS measurements of the study subjects showed a decrease in anterior joint space (AJS) values over time. There was no difference in JS measurements between the groups at T1 and T2. AJS values measured at T1 were lower in the CO group than in the NCO group, but the difference was not statistically significant. In both groups, a posterior position of the mandibular condyle was initially observed with high frequency. However, there is a statistically significant difference in CBCT images taken after occlusal changes, with an increased frequency of condyles observed in the anterior or central positions. Conclusions: In conclusion, AJS decreased over time in TMJ OA, and the mandibular condyle became more anteriorly positioned with occlusal changes. Therefore, clinicians should diligently monitor mandibular condyle morphology and JS using CBCT, along with the patient's clinical symptoms, to treat and control TMJ OA effectively.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.4
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• pp.230-243
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• 2023

Objective: High temperatures can trigger cellular oxidative stress and disrupt spermatogenesis, potentially leading to male infertility. We investigated the effects of retinoic acid (RA), chitosan nanoparticles (CHNPs), and retinoic acid loaded with chitosan nanoparticles (RACHNPs) on spermatogenesis in mice induced by scrotal hyperthermia (Hyp). Methods: Thirty mice (weighing 25 to 30 g) were divided into five experimental groups of six mice each. The groups were as follows: control, Hyp induced by a water bath (43 ℃C for 30 minutes/day for 5 weeks), Hyp+RA (2 mg/kg/day), Hyp+CHNPs (2 mg/kg/72 hours), and Hyp+RACHNPs (4 mg/kg/72 hours). The mice were treated for 35 days. After the experimental treatments, the animals were euthanized. Sperm samples were collected for analysis of sperm parameters, and blood serum was isolated for testosterone measurement. Testis samples were also collected for histopathology assessment, reactive oxygen species (ROS) evaluation, and RNA extraction, which was done to compare the expression levels of the bax, bcl2, p53, Fas, and FasL genes among groups. Additionally, immunohistochemical staining was performed. Results: Treatment with RACHNPs significantly increased stereological parameters such as testicular volume, seminiferous tubule length, and testicular cell count. Additionally, it increased testosterone concentration and improved sperm parameters. We observed significant decreases in ROS production and caspase-3 immunostaining in the RACHNP group. Moreover, the expression levels of bax, p53, Fas, and FasL significantly decreased in the groups treated with RACHNPs and RA. Conclusion: RACHNPs can be considered a potent antioxidative and antiapoptotic agent for therapeutic strategies in reproductive and regenerative medicine.

• Anatomy and Cell Biology
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• v.57 no.1
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• pp.97-104
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• 2024

Heavy reliance on glucose metabolism and a reduced capacity to use ketone bodies makes glioblastoma (GBM) a promising candidate for ketone-based therapies. Ketogenic diet (KD) is well-known for its promising effects in controlling tumor growth in GBM. Moreover, synthetic ketone ester (KE) has demonstrated to increase blood ketone levels and enhance animal survival in a metastatic VM-M3 murine tumor model. Here, we compared the efficacy of a KE-supplemented Atkins-type diet (ATD-KE) to a classic KD in controlling tumor progression and enhancing survival in a clinically relevant orthotopic patient-derived xenograft GBM model. Our findings demonstrate that ATD-KE preserves body weight (percent change from the baseline; 112±2.99 vs. 116.9±2.52 and 104.8±3.67), decreases blood glucose (80.55±0.86 vs. 118.6±9.51 and 52.35±3.89 mg/dl), and increases ketone bodies in blood (1.15±0.03 mM vs. 0.55±0.04 and 2.66±0.21 mM) and brain tumor tissue (3.35±0.30 mM vs. 2.04±0.3 and 4.25±0.25 mM) comparable to the KD (results presented for ATD-KE vs. standard diet [STD] and KD, respectively). Importantly, the ATD-KE treatment significantly enhanced survival compared to the STD and was indistinguishable from the KD (47 days in STD vs. 56 days in KD and ATD-KE), suggesting that a nutritionally balanced low carbohydrate ATD combined with KE may be as effective as the KD alone in reducing brain tumor progression. Overall, these data support the rationale for clinical testing of KE-supplemented low-carb diet as an adjunct treatment for brain tumor patients.

• Clinical and Experimental Reproductive Medicine
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• v.51 no.2
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• pp.102-111
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• 2024

Objective: Given the noteworthy implications of alcohol consumption and its association with male infertility, there has been a notable focus on investigating natural alternatives to mitigate its adverse effects. Thus, this study was conducted to assess the potential protective effect of phycocyanin extract derived from the blue algae Arthrospira (Spirulina) platensis against ethanol-induced oxidative stress, disturbances in testicular morphology, and alterations in sperm production. Methods: Male rats were divided into four groups (five rats each): the control group received a saline solution, the ethanol exposed group (EtOH) was subjected to intraperitoneal injections of 10 mL/kg of ethanol solution at a concentration of 38% (v/v), the phycocyanin alone treated group (P) received oral administration of phycocyanin at a dosage of 50 mg/kg, and the phycocyanin-cotreated group (PE) was given oral phycocyanin followed by ethanol injections. All treatments were administered over a period of 14 days. Results: Our findings demonstrated that ethanol exposure induced reproductive toxicity, characterized by reduced sperm production and viability, alterations in testicular weight and morphology, increased lipid peroxidation levels, and elevated oxidative enzyme activity. In addition, the ethanol-intoxicated group showed perturbations in serum biochemical parameters. However, the simultaneous exposure to ethanol and phycocyanin exhibited a counteractive effect against ethanol toxicity. Conclusion: The results showed that supplementation of phycocyanin prevented oxidative and testicular morphological damage-induced by ethanol and maintained normal sperm production, and viability.

• Oncology Reports
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• v.43 no.2
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• pp.655-661
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• 2020

Alterations in DNA methylation have a central role in the development and outcome of most human malignancies. Non-small cell lung cancer (NSCLC), the most common lung cancer, leads to the largest number of cancer-related deaths worldwide. FBJ murine osteosarcoma viral oncogene homolog B (FOSB) is a key component of the activator protein-1 transcription factor and regulates gene networks associated within oncogenic transformation. The role of FOSB in the development of NSCLC is still elusive. Therefore, the methylation status of the FOSB gene was investigated in NSCLC and its clinical significance in NSCLC progression was evaluated. The methylation status of the promoter and exon 4 regions of the FOSB gene were analyzed in 176 NSCLC specimens by bisulfite pyrosequencing and the association between FOSB methylation status and patient survival was investigated. Compared to adjacent non-malignant tissues, FOSB promoter exhibited exclusive unmethylation in all malignant tissues and the exon 4 region was found unmethylated in 18 (10.2% of the total) tumor samples. Exon 4 unmethylation was associated with downregulation of its mRNA and tended to occur in patients with lymph node metastasis. Univariate and multivariate analyses revealed that exon 4 unmethylation was significantly associated with unfavorable overall survival in patients with stage II-IIIA NSCLC (log-rank P=0.05, adjusted hazard ratio=2.43, 95% confidence interval=1.04-5.68, P=0.04). FOSB was identified as a novel gene with tumor-specific gene body unmethylation in NSCLC and a novel predictive biomarker for NSCLC prognosis. Moreover, the present results indicated that FOSB may have a tumor suppressor function in the progression of NSCLC.

• Physical Therapy Rehabilitation Science
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• v.13 no.3
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• pp.261-273
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• 2024

Background: Several studies have found an association between cervical spinal mobilizations (CSMob) and cervical spinal manipulations (CSM) on pain perception, disability, and satisfaction. However, choosing the proper technique continues to be a challenge for many practitioners. Objectives: To study the effects of a single session of cervical spinal mobilization versus cervical spinal manipulation on pain, disability, and satisfaction. Design: Randomized clinical trial. Methods: 36 subjects with acute and non-specific mechanical neck pain were randomly assigned to one of 3 groups (CSMob, CSM, or control). Outcome measures using the Neck Disability Index (NDI), Numeric Pain Rate Scale (NPRS), and Global Rate of Change (GROC) were quantified at baseline, 5-minutes post, and 4 days post corresponding intervention. Results: The CSM group showed significant increase in GROC (p=0.025) compared to the CSMob and control groups (p=0.472 and p=0.176 respectively) over time. There was a significant decrease in NPRS for the CSM and CSMob groups (p=0.002 and p=<0.001) and a non-significant decrease in NPRS (p=0.642) in the control group over time. Similarly, there was a significant decrease in NDI for the CSM and CSMob groups (p=<0.001 and p=<0.001) and a non-significant decrease in NDI (p=0.084) in the control group over time. Conclusion: Our study findings suggest that skilled manual therapy interventions can be a viable and effective treatment option for reducing neck pain, disability, and perceived favorable change following a single session on subjects with acute, non-specific mechanical neck pain.

• Anatomy and Cell Biology
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• v.55 no.2
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• pp.239-246
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• 2022

We aimed to investigating the effects of metformin (MET) in combination with alpha lipoic acid (ALA) on hormonal and biochemical parameters, in polycystic ovary syndrome (PCOS) women undergoing intracytoplasmic sperm injection (ICSI). This experimental pilot study with a randomized design was carried out on 40 PCOS women in two groups: (1) MET group, administered 1,500 mg/day MET, and (2) MET (1,500 mg/day)+ALA (1,800 mg/day) group. Drugs were administered from the third day of the previous cycle until the day of oocyte aspiration (six weeks of treatment in total). MET+ALA significantly increased the number of maturated oocytes and the rate of fertilization when compared to the MET group. Combination MET+ALA could increase significantly the number of oocytes retrieval and the number of good-quality embryos. Also, the malondialdehyde (MDA) level decreased significantly in the MET+ALA group and the total antioxidant capacity (TAC) level increased significantly in the MET+ALA group compared to the MET group. Also, fasting blood sugar (FBS), insulin, luteinizing hormone (LH), and LH/follicle stimulating hormone (FSH) levels were significantly lower in the MET+ALA group. The pregnancy outcomes showed no significant difference in the rates of biochemical pregnancy, clinical pregnancy, miscarriage, and live births between the control and study groups. The combination of MET+ALA treatment could moderate the complications of PCOS and subsequently improve oocyte and embryo quality.

• Journal of Chest Surgery
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• v.36 no.3
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• pp.182-188
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• 2003

Background: Although ramicotomy (division of the rami communicantes of the thoracic sympathetic ganglia) is a selective and physiological surgical method for essential hyperhidrosis, it has some problems such as higher recurrence rates and the different surgical results among the patients and between left and right sides in the same individual. As one of the factors that are related to the differences in surgical result and recurrences, we investigated the anatomical variations of the rami communicantes. The purpose of this study is to help develop new surgical methods to decrease surgical differences among the patients or between the left and right sides of the same individual and recurrence rates in the clinical application of ramicotomy. Material and Method: We dissected 118 thoracic sympathetic chains in 59 adult Korean cadavers (male: 33, female: 26) to examine the anatomical variations of the rami communicantes from the second to the fourth thoracic sympathetic ganglia that have major components innervating to the hands. After the dissection of bilateral thoracic sympathetic chains, we compared the anatomy of left and right sides and examined the anatomical variations of rami communicantes. Result: The number and variation of communicating rami connecting the spinal nerves and the second sympathetic thoracic ganglion were much larger than lower levels. There was considerably less variability in the anatomy of the rami communicantes at successive levels. Among the 59 cadavers dissected, only 14.3% (9/59) had similar anatomy of thoracic sympathetic chains at both sides. As the components related to the essential palmar hyperhidrosis, intrathoracic nerve of Kuntz from the second thoracic sympathetic ganglion to the first intercostal nerve or brachial plexus were observed in 55.9% (66/118). The incidence of descending rami communicates from the second thoracic sympathetic ganglion to the third intercostal nerve and from the third thoracic sympathetic ganglion to the fourth intercostal nerve were 49.2% (58/118) and 28.0% (33/118). And the incidence of ascending rami communicates from the third thoracic sympathetic ganglion to the second intercostal nerve and from the fourth thoracic sympathetic ganglion to the third intercostal nerve were 6.8% (8/118) and 3.4% (4/118), respectively. Conclusion: Based on the various anatomical evidences of the rami communicantes from this study, only the ramicotomy at the third sympathetic ganglion level is insufficient for the treatment of the essential palmar hyperhidrosis to decrease the difference of surgical results and recurrences. When one is planning to perform the ramicotomy for the essential palmar hyperhidrosis, it is advantageous to divide the intrathoracic nerve of Kuntz on the second rib and the descending or ascending rami communicantes on the third and the fourth ribs as well as all the communicating rami from the third sympathetic ganglion.