• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2757-2760
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• 2016

Gastric cancer (GC) is the fourth most prevalant cancer and the second leading cause of cancer-related mortality worldwide. As in other cancers gastric carcinogenesis is multifactorial involving environmental, genetic and epigenetic components. Epigenetic silencing due to hypermethylation of tumour suppressor genes is one of the key events in gastric carcinogenesis. This study was aimed to analyse the hypermethylation status of the E-Cadherin (CDH1) gene promoter in GCs in the ethnic Kashmiri population. In this study a total of 80 GC patients were recruited. Hypermethylation in tumour tissue was detected by methylation specific PCR (MS-PCR). Hypermethylation of CDH1 promoter was observed in 52 (65%) of gastric carcinoma cases which was significantly much higher than adjacent normal tissue [$p{\leq}0.0001$]. Further the frequency of CDH1 promoter methylation was significantly different with intestinal and diffuse types of gastric cancer [55.7% vs 82.1%; p<0.05]. Moreover females and cases with lymph node invasion had higher frequencies of CDH1 hypermethylation [$P{\leq}0.05$]. Thus the current data indicate a vital role of epigenetic alteration of CDH1 in the causation and development of gastric cancer, particularly of diffuse type, in our population.

• Molecules and Cells
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• v.42 no.2
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• pp.183-188
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• 2019

Osteoarthritis (OA) is a naturally occurring, irreversible disorder and a major health burden. The disease is multifactorial, involving both physiological and mechanical processes, but calcium crystals have been associated intimately with its pathogenesis. This study tested the hypothesis that these crystals have a detrimental effect on the differentiation of osteoclasts and bone homeostasis. This study employed an osteoblastosteoclast coculture system that resembles in vivo osteoblastdependent osteoclast differentiation along with $Ca^{2+}$-phosphate-coated culture dishes. The calcium-containing crystals upregulated the expression of RANKL and increased the differentiation of osteoclasts significantly as a result. On the other hand, osteoblast differentiation was unaffected. MicroRNA profiling showed that dual-specificity phosphatases 1 (DUSP1) was associated with the increased RANKL expression. DUSP1 belongs to a family of MAPK phosphatases and is known to inactivate all three groups of MAPKs, p38, JNK, and ERK. Furthermore, knockdown of DUSP1 gene expression suggested that RANKL expression increases significantly in the absence of DUSP1 regulation. Microarray analysis of the DUSP1 mRNA levels in patients with pathological bone diseases also showed that the downregulated DUSP1 expression leads to increased expression of RANKL and consequently to the destruction of the bone observed in these patients. These findings suggest that calcium-containing crystals may play a crucial role in promoting RANKL-induced osteoclastogenesis via DUSP1.

• Journal of Oral Medicine and Pain
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• v.43 no.4
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• pp.125-130
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• 2018

Purpose: The etiology of temporomandibular disorders (TMDs) is complex and multifactorial including trauma, anatomical, pathophysiological, social and psychological factors. Psychological factors can induce or sustain TMDs in various ways. And psychological problems, such as anxiety and depression can be occurred due to TMDs. Therefore, evaluation of psychological factors in patients with TMDs is important. Although disc displacement (DD) is crucial in clinical situation, most of studies have focused on the relationship of psychosocial factors and myofascial pain. And also, Subtypes of DD can cause different degrees of discomfort, it is necessary to evaluate the psychological states of the patients according to the subtype. The Hospital Anxiety Depression Scale (HADS) is one of the self-report questionnaire to evaluate the psychological factors. HADS-Anxiety (HADS-A) and HADS-Depression (HADS-D) are assessed through 14 questions. The purpose of this study was to evaluate anxiety and depression assessed by HADS in patients diagnosed with subtypes of DD according to diagnostic criteria for TMDs. Methods: Four hundred thirty nine patients were diagnosed as one of the subtypes of DD. One hundred fourty nine subjects with no symptoms were set as control groups. All of them answered the HADS for Koreans. The cut-off score for anxiety and depression was set a score of 8. The chi-square test was performed to evaluate association between DD and anxiety/depression. Results: There was a significant difference in HADS-D between five groups (p<0.01). However, there was no significant difference in HADS-A. All the DD groups showed a significant difference in HADS-D compared with the control group except the DD without reduction without limited opening group. The DD without reduction with limited opening group showed the highest rates in HADS-D (40.4%). Conclusions: Based on the above results, it is necessary to consider the depression in treatment of the patients with DDs.

• Journal of the korean academy of Pediatric Dentistry
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• v.50 no.2
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• pp.131-141
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• 2023

Dental caries is a multifactorial disease influenced by interactions between teeth, biofilm, dietary factors, and various biological, behavioral, sociocultural, and genetic factors. Recent research has shown that dental caries results from dysbiosis, an imbalance in the oral microbial community, shifting the concept from an infectious disease to a non-communicable disease (NCD). Dental caries shares similarities with other chronic NCDs such as cardiovascular diseases and diabetes, as they all relate to dietary intake, lifestyle habits, and environmental factors. Considering the high prevalence of dental caries and its impact on people's health and quality of life, it is important to understand dental caries as an NCD and develop effective oral health management strategies. Ecological prevention methods and efficient public health policies should be provided to reduce risk factors associated with dental caries.

• Molecules and Cells
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• v.46 no.7
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• pp.420-429
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• 2023

Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.

• Journal of Veterinary Science
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• v.23 no.1
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• pp.10.1-10.12
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• 2022

Background: Dry eye disease (DED) cannot be diagnosed by a single test because it is a multifactorial disorder of the ocular surface. Although studies on various dry eye tests (DETs) in dogs have been reported, standard criteria have not been established except for the Schirmer tear test 1 (STT-1). Objectives: To establish reference values for DETs in dogs with normal STT-1 values (≥ 15 mm/min) and to analyze the correlation between DETs. Methods: The STT-1 was performed in 10 healthy Beagle dogs (20 eyes). After 20 min, interferometry (IF) for estimating the lipid layer thickness (LLT) of the tear film, tear meniscus height (TMH), non-invasive tear breakup time (NIBUT), and meibomian gland loss rate of the upper eyelid (MGLRU) and lower eyelid (MGLRL), were measured using an ocular surface analyzer. Results: Mean values for STT-1, TMH, and NIBUT were as follows: 21.7 ± 3.4 mm/min, 0.41 ± 0.21 mm, and 19.1 ± 9.5 sec, respectively. The most frequent LLT range, measured by IF, was 30-80 nm (11 eyes), followed by 80 nm (5 eyes) and 80-140 nm (4 eyes). MGLRU ≤ 25% was measured in 11 eyes and 26%-50% in 9 eyes; MGLRL ≤ 25% in 8 eyes and 26%-50% in 12 eyes. Besides positive correlation between TMH and NIBUT (P = 0.038), there were no significant associations between DETs. Conclusions: Data obtained in this study provided normative references that could be useful for diagnosing DED and for further research into correlation between DETs in dogs with DED.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.3
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• pp.307-312
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• 2023

Hepatic arterioportal fistulae are abnormal communications between the hepatic artery and portal vein. They are reported to be congenital or acquired secondary to trauma, iatrogenic procedures, hepatic cirrhosis, and hepatocellular carcinoma, but less likely to occur spontaneously. Extrahepatic portal venous obstruction (EHPVO) can lead to pre-hepatic portal hypertension. A spontaneous superimposed hepatic arterioportal fistula can lead to pre-sinusoidal portal hypertension, further exacerbating its physiology. This report describes a young woman with long-standing EHPVO presenting with repeated upper gastrointestinal variceal bleeding and symptomatic hypersplenism. Computed tomography scan demonstrated a cavernous transformation of the portal vein and a macroscopic hepatic arterioportal fistula between the left hepatic artery and portal vein collateral in the central liver. The hepatic arterioportal fistula was associated with a flow-related left hepatic artery aneurysm and a portal venous collateral aneurysm proximal and distal to the fistula, respectively. Endovascular coiling was performed for the hepatic arterioportal fistula, followed by proximal splenorenal shunt procedure. This case illustrates an uncommon association of a spontaneous hepatic arterioportal fistula with EHPVO and the utility of a combined endovascular and surgical approach for managing multifactorial non-cirrhotic portal hypertension in such patients.

• Safety and Health at Work
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• v.15 no.2
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• pp.236-241
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• 2024

Background: Gasoline, a complex mixture of volatile organic compounds is classified as possibly carcinogenic to humans. Gasoline station attendants, consistently exposed to its hazardous components, may face genotoxic effects. This study aimed to assess the influence of varying work shift durations on DNA damage in gasoline station attendants. Methods: Ninety individuals from three locations in southern México were studied. Peripheral blood mononuclear cells (PBMCs) were isolated, and DNA damage was assessed using the comet assay. Demographic, occupational, and lifestyle data were collected. Statistical analyses included t-tests, ANOVA, and Pearson correlation. Results: Significant differences in DNA damage parameters were observed between exposed and unexposed groups. The impact of tobacco, alcohol, and exercise on DNA damage was negligible. Extended work shifts (12 and 24 hours) showed heightened DNA damage compared to 8-hour shifts and the unexposed group. A novel finding revealed a modest but significant correlation between DNA damage and job seniority. Conclusion: The study highlights the intricate relationship between occupational exposure to gasoline components, DNA damage, and work shift lengths. Extended shifts correlate with heightened genotoxic effects, emphasizing the importance of personalized safety measures. The significant correlation between DNA damage and job seniority introduces occupational longevity as a determinant in the genetic health of gasoline station attendants. This discovery has implications for implementing targeted interventions and preventive strategies to safeguard workers' genetic integrity throughout their years of service. The study calls for further exploration of unconsidered factors in understanding the multifactorial nature of DNA damage in this occupational setting.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.104-108
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• 2001

Aging is a senescence and defined as a normal physiologic and structural alterations in almost all organ systems with age. As Leonard Hayflick, one of the first gerontologists to propose a theory of biologic aging, indicated that a theory of aging or longevity satisfies the changes of above conditions to be universal, progressive, intrinsic and deleterious. Although a number of theories have been proposed, it is now clear that cell aging (cell senescence) is multifactorial. No single mechanism can account for the many varied manifestations of biological aging. Many theories have been proposed in attempt to understand and explain the process of aging. Aging is effected in individual by genetic factors, diet, social conditions, and the occurrence of age-related diseases as diabetes, hypertension, and arthritis. It involves an endogenous molecular program of cellular senescence as well as continuous exposure throughout life to adverse exogenous influences, leading to progressive infringement on the cell's survivability so called wear and tear. So we could say the basic mechanism of aging depends on the irreversible and universal processes at cellular and molecular level. The immediate cause of these changes is probably an interference in the function of cell's macromolecules-DNA, RNA, and cell proteins-and in the flow of information between these macromolecules. The crucial questions, unanswered at present, concerns what causes these changes in truth. Common theories of aging are able to classify as followings for the easy comprehension. 1. Biological, 1) molecular theories - a. error theory, b. programmed aging theory, c. somatic mutation theory, d. transcription theory, e. run-out-of program theory, 2) cellular theories - a. wear and tear theory, b. cross-link theory, c. clinker theory, d. free radical theory, e. waste product theory, 3) system level theory-a. immunologic/autoimmune theory, 4) others - a. telomere theory, b. rate of living theory, c. stress theory, etc. Prevention of aging is theoretically depending on the cause or theory of aging. However no single theory is available and no definite method of delaying the aging process is possible by this moment. The most popular action is anti-oxidant therapy using vitamin E and C, melatonin and DHEA, etc. Another proposal for the reverse of life-span is TCP-17 and IL-16 administration from the mouse bone marrow B cell line study for the immunoglobulin VDJ rearrangement with RAG-1 and RAG-2. Recently conclusional suggestion for the extending of maximum life-span thought to be the calory restriction.

• Journal of Acupuncture Research
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• v.33 no.2
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• pp.135-150
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• 2016

Objectives : The aim of this study is to review the combination effects and adverse effects of Yerba Mate (Ilex paraguariensis) on the treatment of obesity. Methods : Four databases were searched, including Pubmed, National assembly library, RISS4u, and NDSL, for studies published before March 31, 2016 using the keywords 'yerba mate', 'Ilex paraguariensis', and those related to 'obesity'. Clinical trials, and both in vivo and in vitro studies were classified according to the following categories: publication year, nationality, types and composition of test compounds, combination effects, adverse effects, and safety. Results : A total of 16 articles (14 clinical trials, one in vivo, one in vitro) were included in the analysis. Combination effects were reported from six YGD (Yerba Mate, Guarana, Damiana, Zotrim), five Meltdown, one Shred-matrix, one DBX (DymaBurn Xtreme), one XSIII research study, and adverse effects were reported from two YGD (Zotrim), four Meltdown, one Shred-matrix and one MetEF research study. YGD and Shred-matrix increased satiety while YGD and MetEF had adverse gastrointestinal effects potentially due to guarana. Meltdown and Shred-matrix increased energy expenditure and fat oxidation and had the adverse effects of increased heart rate and blood pressure due to the thermogenic effect of caffeine and yohimbine. DBX increased resting energy expenditure but no difference was observed in respiratory exchange ratio. XSIII reduced body weight gain and food intake more than each of the extracts did on their own. Conclusion : Taken together, the combination effects and adverse effects differed according to the composition of test compounds and the ratio of ingredients. Multicomponent approaches should be used for treating multifactorial diseases such as obesity. As a general conclusion, there is a place for a combination of herbal components including yerba mate, based on the principle of Kun-Shin-Choa-Sa for the treatment of obesity.