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Fibroblast growth factors: Potential novel targets for regenerative therapy of osteoarthritis
Tsung-Ming Chen, Ya-Huey Chen, H Sunny Sun, Shaw-Jenq Tsai
January-February 2019, 62(1):2-10
DOI:10.4103/CJP.CJP_11_19  PMID:30942193
Osteoarthritis (OA) is a degenerative joint disorder and is the leading cause of disability of people, which negatively impact people's physical and mental health. Although OA causes great socioeconomic burden and individual suffering, no effective treatment options are provided so far. This is partially resulted from poor regenerative activity of articular cartilage and our incomplete understanding of the underlying mechanism of OA. Traditional drug therapies such as acetaminophen and opioids are effective in relieving pain but do not reverse cartilage damage and are often associated with adverse events. Therefore, it is necessary to find effective OA drugs. In recent years, novel regenerative therapies have received much attention because they can effectively promote tissue repair and regeneration. The fibroblast growth factor (FGF) signaling has been suggested to involve in cartilage homeostasis for decades. The current research shows that sprifermin/recombinant FGF18 significantly reduces the loss of cartilage thickness and volume without serious side effects, thus warrants a continued research for potential new medications of OA. This review mainly highlights the current research progress on FGFs and FGF receptors as a potential therapeutic target for OA.
  10,077 1,127 18
Combination of exercise training and resveratrol attenuates obese sarcopenia in skeletal muscle atrophy
Chyi-Huey Bai, Javad Alizargar, Ching-Yi Peng, Jia-Ping Wu
May-June 2020, 63(3):101-112
DOI:10.4103/CJP.CJP_95_19  PMID:32594063
Obese sarcopenia is a progressive loss of skeletal muscle mass and strength with increases in adipocytes. The aim of this study was to investigate the effects of combination of exercise training and resveratrol on the pathological pathway from obesity to sarcopenia, and potential therapy for skeletal muscle declines in physical function. Two animal models were experimented: (1) C57BL/6J male mice were fed either a high-fat diet (HFD) for 8 weeks to induce obesity and resveratrol (low-, middle-, and high-dose) for 4 weeks. (2) senescence-accelerated mouse prone 8 (SAMP8) mice with sarcopenia were used. Skeletal muscle function of SAMP8 mice expressed an age-associated decline. In SAMP8 mice, resveratrol (150 mg/Kg BW, daily) was administered by oral gavage two times a week for 1 month of the experimental period. Exercise training based on adaptations in the muscle is training twice a week for 4 weeks. SAMP8 mouse skeletal muscle in each group was analyzed by H and E staining, transferase dUTP nick end labeling, and Western blot analysis. Mitochondrial function expression, apoptosis and relative hypertrophy signaling in HFD-induced obesity mice and SAMP8 mice were determined by Western blot analysis. Results of the present study indicate that effect of resveratrol on skeletal muscles of HFD-induced obesity mice is linked to an increase in Bcl-2 and phosphatidylinositol 3 kinase/AKT expressions. On the other hand, resveratrol, and its combination with exercise training, attenuate the aging-related mitochondrial dysfunction involving Bad, caspase 3, and interleukin-6 expressions in SAMP8 mice. Combination of exercise training and resveratrol induced hypertrophy in skeletal muscles of sarcopenia SAMP8 mice. Therefore, we suggest combination of exercise training and resveratrol as a therapeutic potential in obese sarcopenia.
  8,803 1,252 10
Action of chlorzoxazone on Ca2+movement and viability in human oral cancer cells
Ti Lu, Wei-Zhe Liang, Lyh-Jyh Hao, Chun-Chi Kuo, Pochuen Shieh, Chiang-Ting Chou, Chung-Ren Jan
May-June 2019, 62(3):123-130
DOI:10.4103/CJP.CJP_20_19  PMID:31249266
Chlorzoxazone is a skeletal muscle relaxant. However, the effect of chlorzoxazone on intracellular Ca2+ concentrations ([Ca2+]i) in oral cancer cells is unclear. This study examined whether chlorzoxazone altered Ca2+ signaling and cell viability in OC2 human oral cancer cells. [Ca2+]iin suspended cells was measured using the fluorescent Ca2+-sensitive dye fura-2. Cell viability was examined by water-soluble tetrazolium-1 assay. Chlorzoxazone (250–1000 μM) induced [Ca2+]irises in a concentration-dependent manner. Ca2+ removal reduced the signal by approximately 50%. Mn2+ has been shown to enter cells through similar mechanisms as Ca2+ but quenches fura-2 fluorescence at all excitation wavelengths. Chlorzoxazone (1000 μM) induced Mn2+ influx, suggesting that Ca2+ entry occurred. Chlorzoxazone-induced Ca2+ entry was inhibited by 20% by inhibitors of store-operated Ca2+ channels and protein kinase C (PKC) modulators. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) inhibited chlorzoxazone-evoked [Ca2+]irises by 88%. Conversely, treatment with chlorzoxazone-suppressed TG-evoked [Ca2+]irises 75%. Chlorzoxazone induced [Ca2+]irises by exclusively releasing Ca2+ from the endoplasmic reticulum. Inhibition of phospholipase C (PLC) with U73122 did not alter chlorzoxazone-induced [Ca2+]irises. PLC activity was not involved in chlorzoxazone-evoked [Ca2+]irises. Chlorzoxazone at 200–700 μM decreased cell viability, which was not reversed by pretreatment with Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl. In sum, in OC2 cells, chlorzoxazone induced [Ca2+]irises by evoking PLC-independent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Chlorzoxazone also caused Ca2+-independent cell death. Since [Ca2+]irises play a triggering or modulatory role in numerous cellular phenomena, the effect of chlorzoxazone on [Ca2+]iand cell viability should be taken into account in other in vitro studies.
  7,553 489 4
Blood dopamine level enhanced by caffeine in men after treadmill running
Jeong-Beom Lee, Hye-Jin Lee, Seung-Jea Lee, Tae-Wook Kim
November-December 2019, 62(6):279-284
DOI:10.4103/CJP.CJP_59_19  PMID:31793465
The aim of this study was to investigate the plasma dopamine and serum serotonin levels in humans with and without caffeine (CAFF) ingestion during treadmill running exercise. Thirty male volunteers participated in the randomized experiment involving two groups: CON (n = 15, 200 mL of tap water) versus CAFF (n = 15, 3 mg/kg CAFF and 200 mL tap water). After treadmill running, the dopamine level was significantly increased in the CAFF group (P < 0.01) and was significantly higher than in the CON group (P < 0.01). Serotonin was significantly increased in both groups after treadmill running (P < 0.05). However, serotonin levels showed no significant statistical difference between the groups. Prolactin and cortisol were significantly increased in both groups after treadmill running (P < 0.01). However, there was no significant statistical difference between groups. β-endorphin level was significantly increased in the CAFF group at after treadmill running (P < 0.01) and was significantly higher than in CON after treadmill running (P < 0.01). In conclusion, 3 mg/kg CAFF ingestion before treadmill running stimulated dopamine release without inhibiting serotonin, which may reduce central fatigue.
  7,110 833 3
Physiological and pathological functions of beta-amyloid in the brain and alzheimer's disease: A review
Ladislav Volicer
May-June 2020, 63(3):95-100
DOI:10.4103/CJP.CJP_10_20  PMID:32594062
Alzheimer's disease is a major health problem all over the world. The role of beta-amyloid (Aβ) is at the center of investigations trying to discover the disease pathogenesis and to develop drugs for treatment or prevention on Alzheimer's disease. This review summarizes both physiological and pathological functions of Aβ and factors that may participate in the disease development. Known genetic factors are trisomy of chromosome 21, mutations of presenilin 1 and 2, and apolipoprotein E4. Lifetime stresses that increase the risk of development of Alzheimer's disease are described. Another important factor is the level of education, especially of linguistic ability. Lifestyle factors include mental and physical exercise, head injury, social contacts, and diet. All these factors might potentiate the effect of aging on the brain to increase the risk of development of pathological changes. The review summarizes pathological features of Alzheimer brain, Aβ plaques, neurofibrillary tangles composed of hyperphosphorylated tau, and brain atrophy. Consequences of Alzheimer's disease that are reviewed include cognitive deficit, loss of function, and neuropsychiatric symptoms. Because there is no effective treatment, many persons with Alzheimer's disease survive to severe and terminal stages which they may fear. Alzheimer's disease at this stage should be considered a terminal disease for which palliative care is indicated. Importance of advance directives, promoting previous wishes of the person who was developing dementia and who subsequently lost decision-making capacity, and limitations of these directives are discussed. Information in this review is based on author's knowledge and clinical experience that were updated by searches of PubMed.
  7,042 862 6
Acute and chronic effects of aerobic exercise on serum irisin, adropin, and cholesterol levels in the winter season: Indoor training versus outdoor training
Serhat Ozbay, Süleyman Ulupınar, Engin Şebin, Konca Altınkaynak
January-February 2020, 63(1):21-26
DOI:10.4103/CJP.CJP_84_19  PMID:32056983
The aim of this study is to investigate the acute and chronic effects of aerobic training performed indoors and outdoors on irisin, adropin, and cholesterol levels in winter. Thirty-two healthy males participated in this study. Participants were divided into two groups: outdoor group (n = 16) and indoor group (n = 16). They then performed 40-min aerobic running exercises 4 days/week for 18 weeks. The outdoor group trained at −5°C–5°C environmental temperature, while the indoor group trained at 21°C–25°C. Blood samples were collected before and after the 18-week training period and immediately after the first training. The results showed that single aerobic exercise induced minimal increase in serum irisin concentrations in both groups. In addition, irisin levels did not change in the outdoor group but significantly decreased in the indoor group after the 18-week training period. Aerobic exercise had no acute or chronic effects on serum adropin levels in the indoor group. However, the aerobic training caused a decrease in adropin levels chronically, but there was no acute effect after single aerobic exercise in the outdoor group. Furthermore, there was no acute effect on high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and total cholesterol after single aerobic exercise in both groups. However, after the 18-week training period, there was a significant increase in HDL-C levels in both groups. Moreover, the increase in HDL-C in the outdoor group was higher than in the indoor group. Thus, this study provides evidence for the beneficial chronic effects of aerobic exercise and cold on HDL-C levels as well as the beneficial acute effects on irisin concentrations.
  6,862 946 17
Beneficial effects of a negative ion patch on eccentric exercise-induced muscle damage, inflammation, and exercise performance in badminton athletes
Chin-Shan Ho, Mon-Chien Lee, Chi-Yao Chang, Wen-Chyuan Chen, Wen-Ching Huang
January-February 2020, 63(1):35-42
DOI:10.4103/CJP.CJP_33_19  PMID:32056985
Complementary and alternative medicines (CAMs) are widely applied and accepted for therapeutic purposes because of their numerous benefits. Negative ion treatment belongs to one of the critical categories defined by the National Center for CAM, with such treatment capable of air purification and ameliorating emotional disorders (e.g., depression and seasonal affective disorder). Negative ions can be produced naturally and also by a material with activated energy. Exercise-induced muscle damage (EIMD) often occurs due to inadequate warm up, high-intensity exercise, overload, and inappropriate posture, especially for high-intensive competition. Few studies have investigated the effects of negative ion treatment on muscular injury in the sports science field. In the current study, we enrolled badminton athletes and induced muscle damage in them through eccentric exercise in the form of a high-intensity squat program. We evaluated the effects of negative ion patches of different intensities at three points (preexercise, postexercise, and recovery) by analyzing physiological indexes (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-10, creatine kinase [CK], and lactate dehydrogenase [LDH] levels) and performing a functional assessment (a countermovement jump [CMJ] test). We found that a high-intensity negative ion patch could significantly reduce the levels of TNF-α, an injury-associated inflammatory cytokine, and related markers (CK and LDH). In addition, muscular overload-caused fatigue could be also ameliorated, as indicated by the functional CMJ test result, and related muscular characteristics (tone and stiffness) could be effectively improved. Thus, the negative ion treatment could effectively improve physiological adaption and muscular fatigue recovery after EIMD in the current study. The negative ion patch treatment can be further integrated into a taping system to synergistically fulfill exercise-induced damage protection and functional elevation. However, the effects of this treatment require further experimental validation.
  5,923 880 6
Neuropeptide FF modulates neuroendocrine and energy homeostasis through hypothalamic signaling
Ya-Tin Lin, Jin-Chung Chen
March-April 2019, 62(2):47-52
DOI:10.4103/CJP.CJP_23_19  PMID:31243174
Neuropeptide FF (NPFF) is known as a morphine-modulating peptide and was first isolated in 1985. It has been characterized as an RF-amide peptide. The traditional role of NPFF is mediation of the pain response, and it displays both anti-opioid and pro-opioid actions through central nervous system. In the recent decade, additional evidence has revealed some untraditional features of NPFF, such as regulation of the neuroendocrine system, energy homeostasis, anti-inflammation, pain transmission, and peripheral modulation of adipose tissue macrophages. Neuropeptide FF receptor 2 (NPFFR2) is a physiological receptor of NPFF, and the actions of NPFF may occur through downstream NPFFR2 signaling. NPFF and NPFFR2 increase the neuronal activity in various areas of the hypothalamus to modulate the hypothalamic–pituitary–adrenal axis, the autonomic nervous system, food intake, and energy balance. These underlying cellular mechanisms have been explored in the past few years. Here, we review the impact of NPFF and related RF-amide peptides on hypothalamic function. The interaction of NPFF with NPFFR2 in the hypothalamus is emphasized, and NPFF-NPFFR2 system may represent an important therapeutic target in hypothalamic-related disorders in the future.
  5,847 728 18
Formosan wood mice (Apodemus semotus) exhibit more exploratory behaviors and central dopaminergic activities than C57BL/6 mice in the open field test
Kun-Ruey Shieh, Shu-Chuan Yang
January-February 2020, 63(1):27-34
DOI:10.4103/CJP.CJP_47_19  PMID:32056984
Three-quarters of the lands in Taiwan are over 1000 m above sea level. Formosan wood mice (Apodemus semotus), also called Taiwanese field mice, are largely found at altitudes of 1400 ~ 3700 m and are the dominant rodents in these areas. Notably, Formosan wood mice show high levels of exploratory behaviors, not only in the wild but also in laboratory situations. Therefore, in this study, we examined the behavioral responses and central dopaminergic activities of male C57BL/6J mice and Formosan wood mice in the open field test. Dopamine and its major metabolite 3,4-dihydroxyphenylacetic acid were used as indices of dopaminergic activities. Formosan wood mice showed higher levels of exploration and locomotor activity than C57BL/6J mice in the open field test. Higher central dopaminergic activities in the nucleus accumbens, striatum, and medial prefrontal cortex were found in Formosan wood mice than in C57BL/6J mice in the open field test. Higher levels of locomotion and central dopaminergic activities in Formosan wood mice were consistent after two exposures to the open field test; however, dramatic decreases in levels of locomotion and central dopaminergic activities in C57BL/6J mice were found after two exposures to the open field test. The present study found that Formosan wood mice exhibited higher levels of locomotor activity and exploration and central dopaminergic activities than C57BL/6J mice after one or two exposures to the open field test.
  5,934 625 8
Different susceptibilities of osteoclasts and osteoblasts to glucocorticoid-induced oxidative stress and mitochondrial alterations
Yu-Hsu Chen, Shao-Yu Peng, Ming-Te Cheng, Yu-Pao Hsu, Zong-Xi Huang, Winston Teng-Kuei Cheng, Shinn-Chih Wu
March-April 2019, 62(2):70-79
DOI:10.4103/CJP.CJP_7_19  PMID:31243177
Glucocorticoid-induced bone loss is the most common form of secondary osteoporosis. This toxic effect has not been efficiently managed, possibly due to the incomplete understanding of the extraordinarily diverse cellular responses induced by glucocorticoid treatment. Previous literatures revealed that high dose of exogenous glucocorticoid triggers apoptosis in osteocytes and osteoblasts. This cell death is associated with glucocorticoid-induced oxidative stress. In this study, we aimed to investigate the mechanisms of glucocorticoid-induced apoptosis in osteoblasts and examine the responses of osteoclasts to the synthetic glucocorticoid, dexamethasone. We demonstrated the biphasic effects of exogenous glucocorticoid on osteoblastic mitochondrial functions and elevated intracellular oxidative stress in a dose- and time-dependent manner. On comparison, similar treatment did not induce mitochondrial dysfunctions and oxidative stress in osteoclasts. The production of reactive oxygen/nitrogen species was decreased in osteoclasts. The differences are not due to varying efficiency of cellular antioxidant system. The opposite effects on nitrogen oxide synthase might provide an explanation, as the expression levels of nos2 gene are suppressed in the osteoclast but elevated in the osteoblast. We further revealed that glucocorticoids have a substantial impact on the osteoblastic mitochondria. Basal respiration rate and ATP production were increased upon 24 h incubation of glucocorticoids. The increase in proton leak and nonmitochondrial respiration suggests a potential source of glucocorticoid-induced oxidative stress. Long-term incubation of glucocorticoids accumulates these detrimental changes and results in cytochrome C release and mitochondrial breakdown, consequently leading to apoptosis in osteoblasts. The mitochondrial alterations might be other sources of glucocorticoid-induced oxidative stress in osteoblasts.
  5,788 698 9
Effect of taurine on ethanol-induced oxidative stress in mouse liver and kidney
Zofia Goc, Edyta Kapusta, Grzegorz Formicki, Monika Martiniaková, Radoslav Omelka
July-August 2019, 62(4):148-156
DOI:10.4103/CJP.CJP_28_19  PMID:31535630
The purpose of this study was to investigate the effect of alcohol exposure on liver and kidney antioxidant systems in taurine exhibition during different time periods. Mice were divided into groups: I – control; II – alcohol (2.5 g/kg b.w.); III – taurine (42.84 mg/kg b.w.); and IV – alcohol + taurine. Treatments were provided for 24 h, 14 days, and 56 days. In the liver and kidney of the alcohol group, antioxidant enzyme (superoxide dismutase, catalase, and glutathione peroxidase) activities, reduced glutathione (GSH), and malondialdehyde (MDA) levels were decreased, as compared to the control group in all time periods. Taurine was found to be effectively inhibiting oxidative action of alcohol and increasing all the tested parameters in the liver (after 24 h) and kidney (after 24 h and 14 days). Moreover, the positive effect of taurine administration on GSH and MDA levels persisted in the kidneys of mice exposed to alcohol for 56 days. In conclusion, alcohol administration led to a significant influence on antioxidant system in the liver and kidney, but simultaneous intake of taurine, along with ethanol, partly attenuated the antioxidant changes in these organs.
  5,828 614 15
Histone deacetylases in stroke
Mei-Han Kao, Teng-Nan Lin
May-June 2019, 62(3):95-107
DOI:10.4103/CJP.CJP_22_19  PMID:31249263
Stroke is the second leading cause of death and the leading cause of adult disability worldwide. Despite an impressive amount of neuroprotective agents that has been identified in experimental stroke, none of them proved efficient in clinical trials. There is a general consensus that an effective treatment requires the ability to interact with not one, but multiple pathophysiological cascades at different levels that induced by the insult – cocktail therapy. Luckily, recent progress in the field of epigenetics revealed that epigenetic modifications had influence on many known pathways involved in the complex course of ischemic disease development. The fact that epigenetic molecules, by altering transcriptional regulation, may simultaneously act on different levels of ischemic brain injury makes them promising candidates for clinical use. These modifications arise typically owing to deoxyribonucleic acid methylation and histone acetylation. The aim of this review is to give a comprehensive overview of current advances in stroke epigenetics, in particular, the physiological and pathological functions of the 11 classical histone deacetylases.
  5,426 695 10
Glycine tomentella hayata extract and its ingredient daidzin ameliorate cyclophosphamide-induced hemorrhagic cystitis and oxidative stress through the action of antioxidation, anti-fibrosis, and anti-inflammation
Kung-Chieh Wu, Wei-Yu Lin, Yi-Ting Sung, Wei-Yi Wu, Yu-Hsiuan Cheng, Tung-Sheng Chen, Bing-Juin Chiang, Chiang-Ting Chien
September-October 2019, 62(5):188-195
DOI:10.4103/CJP.CJP_60_19  PMID:31670282
We explored the therapeutic potential of intragastric administration of traditional Chinese medicine Glycine tomentella Hayata (I-Tiao-Gung [ITG]) extract and its major component Daidzin on cyclophosphamide (CYP)-induced cystitis, oxidative stress, fibrosis, inflammation, and bladder hyperactivity in rats. Female Wistar rats were divided into control, CYP (200 mg/kg), CYP+ITG (1.17 g/kg/day), and CYP+Daidzin (12.5 mg/kg/day) groups. We measured the voiding function by the transcystometrogram and evaluated the pathology with the hematoxylin and eosin and Masson stain. We determined the bladder reactive oxygen species (ROS) amount by an ultrasensitive chemiluminescence analyzer, the expression of 3-nitrotyrosine (3-NT) and NADPH oxidase 4 (NOX4) by Western blot and the expression of multiple cytokine profiles, including matrix metalloproteinase (MMP)-8 and tissue inhibitor of metalloproteinase (TIMP)-1 through a cytokine array. ITG extract contains 1.07% of Daidzin through high-performance liquid chromatography. The effect of ITG extract and Daidzin in scavenging hydrogen peroxide activity was more efficient than distilled water. CYP-induced higher urination frequency, shorter intercontraction interval, and lower maximal voiding pressure in the bladders and these symptoms were significantly ameliorated in CYP+ITG and CYP+Daidzin groups. The amount of in vivo bladder ROS and the expression of 3-NT and NOX4 expressions were significantly increased in CYP group but were efficiently decreased in the CYP+ITG and CYP+Daidzin groups. CYP-induced fibrosis, hemorrhage, leukocyte infiltration, and edema in the bladders were significantly attenuated in the CYP+ITG and CYP+Daidzin groups. These results suggested that ITG extract and its active component Daidzin effectively improved CYP-induced oxidative stress, inflammation, and fibrosis through inhibiting the MMP-8, TIMP-1, and oxidative stress.
  5,595 500 5
Magnesium sulfate attenuates lipopolysaccharides-induced acute lung injury in mice
Wu Li, Xiaoling Wu, Jialin Yu, Chenjie Ma, Peipei Zhuang, Jin Zeng, Jiamei Zhang, Guangcun Deng, Yujiong Wang
September-October 2019, 62(5):203-209
DOI:10.4103/CJP.CJP_48_19  PMID:31670284
Acute lung injury (ALI) is a common and severe respiratory disease with high morbidity and mortality. Although some progress has been made in the past years, the pathogenesis of ALI is still poorly understood and the therapeutic outcome has still not been significantly improved. It is well-recognized that magnesium sulfate (MgSO4) possesses potent anti-inflammation capacity. The present study was designed to investigate the protective effects of MgSO4 in lipopolysaccharides (LPSs)-induced ALI taken into account that excessive inflammatory response plays critical role in the development of ALI. In this study, Kunming mice were intravenously injected with LPS through tail vein to establish the ALI model and in parallel, A549 cells were used to establish cell model. The lung wet-to-dry weight ratio, malondialdehyde (MDA) levels in lung tissue, lung permeability index, hematoxylin and eosin staining, cytokines in the serum and bronchoalveolar lavage fluid (BALF), neutrophil counts in BALF, LPS-induced A549 cell apoptosis as well as apoptosis-inducing factor (AIF), and Poly(ADP-ribose) polymerase-1 (PARP-1) expression in both mice and A549 cells were detected. Our results demonstrated that MgSO4 significantly attenuated the LPS-induced ALI, oxidative stress (decreased MDA levels), and lung inflammatory response. Moreover, MgSO4 exerted protective effects by mitigating LPS-induced A549 cell apoptosis. Furthermore, MgSO4 decreased the AIF and PARP-1 expression both in vivo and in vitro. Our results, taken together, demonstrated that MgSO4 is a potential therapeutic agent for ALI taken into consideration that MgSO4 is commonly used in clinical settings.
  5,313 506 8
Autophagy: A potential target for rescuing sepsis-induced hepatic failure
Chin Hsu
March-April 2019, 62(2):53-62
DOI:10.4103/CJP.CJP_25_19  PMID:31243175
Sepsis is the leading cause of death in intensive care units worldwide; however, it remains a scientific and clinical challenge in modern medicine. An excessive inflammatory response associated with high level of reactive oxygen species results in mitochondrial dysfunction and activation of the unfolded protein response leading to subsequent energetic organ failure in septic patients. In addition to blocking the inflammatory cascade directly, new strategies focusing on host endogenous adaption to severe infection may hold better promise for improving outcomes in septic patients. Autophagy is a fundamental cellular response to stress and pathogen invasion. The study of autophagic responses to sepsis is a critical component of understanding the mechanisms by which tissues respond to infection. This review aims at elucidating the role of autophagy in sepsis-induced hepatic failure and further explores the possible factor that suppresses autophagy and potential targets of augmenting autophagy, in an effort to provide a new perspective for the clinical treatment of sepsis-induced hepatic failure.
  5,247 556 3
Vitamin C supplementation improves blood pressure and oxidative stress after acute exercise in patients with poorly controlled type 2 diabetes mellitus: A randomized, placebo-controlled, cross-over study
Chongchira Boonthongkaew, Terdthai Tong-Un, Yupaporn Kanpetta, Nisa Chaungchot, Chanvit Leelayuwat, Naruemon Leelayuwat
January-February 2021, 64(1):16-23
DOI:10.4103/cjp.cjp_95_20  PMID:33642340
This study aimed to assess the effect of Vitamin C on blood pressure (BP), and subsequently on oxidative stress and nitric oxide (NO) release, following the low-intensity exercise in the patients. This study included 24 patients with type 2 diabetes mellitus (T2D) (age, 53 ± 7 years; hemoglobin A1c, 10.1% ± 0.9%) randomized into two 6-week daily arms based on the consumption of either placebo or 1000 mg Vitamin C. The crossover trial occurred after a 6-week washout. Before and after both supplementation arms, all patients performed cycling exercise at 33% of peak oxygen consumption for 20 min. BP was measured before, immediately, and 60 min after the exercise. Blood samples were drawn immediately before and after the exercise to determine plasma ascorbate, malondialdehyde (MDA), F2-isoprostanes (F2-IsoPs), and NO concentrations. Data showed significant lower BP in the Vitamin C arm when compared with the placebo arm (systolic BP [SBP] P < 0.001 at every time point, diastolic BP [DBP] P < 0.001 except at immediately after exercise, P < 0.05). Plasma ascorbate concentration (P < 0.05 at every time point) and plasma NO (at resting P < 0.001, immediately after exercise P < 0.05) were significantly increased in the Vitamin C arm than in the placebo arm. Plasma MDA (P < 0.05 at every time point) and F2-IsoPs (P < 0.05 at every time point) concentrations were significantly lower in the Vitamin C arm than in the placebo arm. In addition, data showed significantly lower SBP (P < 0.001 at every time point), DBP (P < 0.001 except at immediately after exercise P < 0.05), plasma MDA (P < 0.001 at every time point), and F2-IsoPs (P < 0.05 at every time point) at post-supplementation than at pre-supplementation. Besides, there were significantly higher plasma ascorbate (P < 0.05 at every time point) and NO (at rest P < 0.01, immediately after exercise P < 0.05) concentrations at post-supplementation than at pre-supplementation. This is in contrast to the placebo treatment arm which demonstrated no statistical difference in all outcomes throughout the experiment. This study suggests that 6-week Vitamin C supplementation decreased preexercise and postexercise BPs, possibly due to improved oxidative stress and NO release. However, exercise had no effect on any outcome measures.
  4,690 1,093 7
Possible nitric oxide mechanism involved in the protective effect of L-theanine on haloperidol-induced orofacial dyskinesia
Cheng-Chia Tsai, Mao-Hsien Wang, Kuo-Chi Chang, Hung-Sheng Soung, Chih-Chuan Yang, Hsiang-Chien Tseng
January-February 2019, 62(1):17-26
DOI:10.4103/CJP.CJP_8_19  PMID:30942195
Having powerful antioxidative properties, L-theanine (LT), one of the major amino acid components in green tea, has potent anti-oxidative and neuroprotective effects. In this study, we examined the potential protective effects of LT on haloperidol (HAL)-induced orofacial dyskinesia (OD) in rats. HAL treatment (1 mg/kg intraperitoneally for 21 days) induced OD; significant increases (P < 0.001) in the frequency of vacuous chewing movement and tongue protrusion as well as the duration of facial twitching. LT treatment (100 mg/kg orally for 35 days, starting 14 days before HAL injection) was able to prevent most of the HAL-induced OD. LT treatment was also able to reduce the lipid peroxidation production and nitric oxide (NO) level, and enhance the antioxidation power in striatum from rats with HAL treatment. In order to examine the implication of NO pathway activity in HAL treatment, either NO precursor (L-arginine) or NO synthase inhibitor (L-NAME) was co-pretreated with LT; NO precursor treatment eliminated the protective effect of LT, in contrast to that NO synthase inhibitor treatment significantly potentiated the LT effects on behavioral and biochemical protection in HAL-treated rats. These results suggested that the NO pathway was implicated, at least in part, in the HAL-induced OD, as well as in the protective effect of LT in treating HAL-induced OD. The above evidence provides a clinically relevant value for LT in delaying or treating tardive dyskinesia.
  5,289 443 5
Interplay of COVID-19 and physiological dysfunctions
Yu-Hsiu Chang, Chih-Heng Huang, Po-Shiuan Hsieh
November-December 2020, 63(6):245-249
DOI:10.4103/CJP.CJP_91_20  PMID:33380608
The outbreak of the global coronavirus disease 2019 (COVID-19) pandemic continues to impact the socioeconomic fabric and the general well-being of numerous populations and communities around the world. As cases continue to rise exponentially, gaining a better understanding of the pathophysiology and the associated clinical implications of SARS-CoV-2, the causative agent of COVID-19, becomes increasingly necessary. In this article, we delineate the role of COVID-19 in physiological and immunological dysfunction. Specifically, we highlight the various possible mechanisms and effects of SARS-CoV-2 infections on major organ systems as well as their contribution toward multiorgan system failure. By analyzing studies and statistics regarding various comorbidities in COVID-19 patients, we make inferences on the linkage between COVID-19, immune injury, multiorgan system damage, and disease progression.
  5,312 389 -
Mechanistic insight of cyclin-dependent kinase 5 in modulating lung cancer growth
G. M. Shazzad Hossain Prince, Tsung-Ying Yang, Ho Lin, Mei-Chih Chen
November-December 2019, 62(6):231-240
DOI:10.4103/CJP.CJP_67_19  PMID:31793458
Lung harbors the growth of primary and secondary tumors. Even though numerous factors regulate the complex signal transduction and cytoskeletal remodeling toward the progression of lung cancer, cyclin-dependent kinase 5 (Cdk5), a previously known kinase in the central nervous system, has raised much attention in the recent years. Patients with aberrant Cdk5 expression also lead to poor survival. Cdk5 has already been employed in various cellular processes which shape the fate of cancer. In lung cancer, Cdk5 mainly regulates tumor suppressor genes, carcinogenesis, cytoskeletal remodeling, and immune checkpoints. Inhibiting Cdk5 by using drugs, siRNA or CRISP-Cas9 system has rendered crucial therapeutic advantage in the combat against lung cancer. Thus, the relation of Cdk5 to lung cancer needs to be addressed in detail. In this review, we will discuss various cellular events modulated by Cdk5 and we will go further into their underlying mechanism in lung cancer.
  4,971 543 4
Tau phosphorylation and cochlear apoptosis cause hearing loss in 3×Tg-AD Mouse Model of Alzheimer's Disease
Sheue-Er Wang, Chung-Hsin Wu
March-April 2021, 64(2):61-71
DOI:10.4103/CJP.CJP_79_20  PMID:33938816
Clinically typical dementia Alzheimer's disease (AD) is associated with abnormal auditory processing. However, possible molecular mechanisms responsible for the auditory pathology of AD patients are not known. According to our past research findings that the thresholds of auditory brainstem response, but not distortion product otoacoustic emissions, were significantly increased in AD mice from 9 months of age and thereafter. Thus, we further explored the possible mechanism of auditory degradation of 3×Tg-AD mice in this study. Our histochemical staining evidence showed the cochlear spiral ganglion neurons (SGN), but not the cochlear hair cells, were lost significantly in the cochlea of 3×Tg-AD mice from 9 months of age and thereafter. Our immunostaining and western blotting evidence showed that phosphorylated tau protein (p-Tau), p-glycogen synthase kinase 3, neurofilament, and apoptosis-related p53, Bcl2-associated X protein, cytochrome c, caspase-9, and caspase-3 were gradually increased, but B-cell lymphoma 2 was gradually decreased with age growth in the cochlea of 3×Tg-AD mice. We suggested that tau hyperphosphorylation and p-Tau 181 aggregation, and mitochondria- and endoplasmic reticulum stress-mediated apoptosis may play a role in the degeneration of SGN in the cochlea. Progressive SGN degeneration in the cochlea may contribute to hearing loss of aging 3×Tg-AD mice.
  4,614 874 4
Distinct patterns of interleukin-12/23 and tumor necrosis factor α synthesis by activated macrophages are modulated by glucose and colon cancer metabolites
Ching-Ying Huang, Linda Chia-Hui Yu
January-February 2020, 63(1):7-14
DOI:10.4103/CJP.CJP_75_19  PMID:32056981
Chronic inflammation is a major risk factor for colitis-associated colorectal carcinoma (CRC). Macrophages play a key role in altering the tumor microenvironment by producing pro-inflammatory and anti-inflammatory cytokines. Our previous studies showed that glucose metabolism conferred death resistance for tumor progression and exerted anti-inflammatory effects in ischemic gut mucosa. However, the effect of glucose and cancer metabolites in modulating macrophage cytokine profiles remains poorly defined. We used an in vitro system to mimic intestinal microenvironment and to investigate the roles of glucose and cancer metabolites in the cross-talk between carcinoma cells and macrophages. Human monocyte-derived THP-1 macrophages were stimulated with bacterial lipopolysaccharide (LPS) in the presence of conditioned media (CM) collected from human CRC Caco-2 cells incubated in either glucose-free or glucose-containing media. Our results demonstrated that glucose modulated the macrophage cytokine production, including decreased LPS-induced pro-inflammatory cytokines (i.e., tumor necrosis factor [TNF]α and interleukin [IL]-6) and increased anti-inflammatory cytokine (i.e., IL-10), at resting state. Moreover, glucose-containing CM reduced the macrophage secretion of TNFα and IL-8 but elevated the IL-12 and IL-23 levels, showing an opposite pattern of distinct pro-inflammatory cytokines modulated by cancer glucose metabolites. In contrast, LPS-induced production of macrophage inflammatory protein-1 (a macrophage-derived chemoattractant for granulocytes) was not altered by glucose or CM, indicating that resident macrophages may play a more dominant role than infiltrating granulocytes for responding to cancer metabolites. In conclusion, glucose metabolites from CRC triggered distinct changes in the cytokine profiles in macrophages. The downregulation of death-inducing TNFα and upregulation of Th1/17-polarizing IL-12/IL-23 axis in macrophages caused by exposure to cancer-derived glucose metabolites may contribute to tumor progression.
  4,742 680 8
Atrial electrical remodeling induced by chronic ischemia and inflammation in patients with stable coronary artery disease
Răzvan Constantin Serban, Alkora Ioana Balan, Marcel Perian, Irina Pintilie, Cristina Somkereki, Adina Huţanu, Alina Scridon
January-February 2019, 62(1):11-16
DOI:10.4103/CJP.CJP_2_19  PMID:30942194
The pathophysiology of coronary artery disease (CAD) includes low-grade chronic inflammation. At its turn, inflammation is known to promote myocardial structural remodeling and to increase vulnerability to atrial arrhythmias. Meanwhile, the impact of chronic inflammation on the electrophysiological properties of the atria remains unknown. We aimed to evaluate the impact of low-grade chronic inflammation on atrial electrophysiology in patients with stable CAD undergoing elective coronary artery bypass grafting (CABG). Circulating levels of several inflammatory, angiogenesis, and endothelial dysfunction markers were determined 1 day before CABG in 30 consecutive CAD patients. Right atrial appendage samples were collected during the CABG procedure; action potential recordings were performed in six study patients using the microelectrode technique. Interleukin (IL)-1b (r = 1.00, P = 0.01), IL-6 (r = 0.98, P < 0.01), vascular endothelial growth factor (VEGF) (r = 0.98, P < 0.01), and hemoglobin (r = 0.98, P < 0.01) levels significantly positively correlated with the duration of atrial depolarization. Consequently, IL-6, VEGF, and hemoglobin (r = −0.86, P = 0.03 for all) levels significantly negatively correlated with the velocity of atrial depolarization. There was no significant correlation between any of the studied markers levels and any of the other parameters of the action potential (all P > 0.05). The present study is the first to demonstrate that in patients with stable CAD, chronic inflammation and ischemia are associated with pro-arrhythmic atrial electrical remodeling. These changes may contribute to the increased propensity to postoperative atrial arrhythmias seen in some of the patients undergoing CABG.
  4,728 528 7
Low-frequency electroacupuncture at acupoints guanyuan (CV4) and zhongji (CV3) lengthen ejaculatory latency and improves sexual behavior in male rats
Andy C Huang, Ming-Che Liu, Tung-Hu Tsai, Ya-Han Chang, Jia-Min Wu, Kuei-Ying Yeh
July-August 2020, 63(4):163-170
DOI:10.4103/CJP.CJP_34_20  PMID:32859883
Acupuncture is a key component of Traditional Chinese Medicine in which needles are inserted into specific areas in the body to stimulate certain physiological reactions of the body. Clinical research shows that acupuncture is beneficial in treating a variety of illnesses, such as erectile dysfunction. Therefore, we investigated the effect of electroacupuncture (EA) stimulation of both low- and high frequencies at Guanyuan (CV4) and Zhongji (CV3) acupoints on male copulatory behavior in sexually experienced male rats. The animals were randomly divided into four groups: control, sham EA, EA, and only acupuncture. The administered low and high EA were 2 Hz and 80 Hz, respectively, for which the respective intensities were 1.5 mA (30 min/day for 5 days) and 1.5 mA (30 min once). The only acupuncture-administered group received acupunctures at CV4 and CV3 without electrical stimulation. Following the acupuncture treatments, copulatory behavior test was conducted. Eventually, animals were sacrificed and blood samples were collected for testing the serum hormonal profile including luteinizing hormone (LH), testosterone (T), and serotonin (5-HT). Results showed that low-frequency EA-treated rats exhibited increasing intromissions and ejaculation latency compared to control, sham EA, and acupuncture groups, while high-frequency EA-treated rats displayed lower intromissions and ejaculation frequency when compared with those in controls. Furthermore, serum levels of 5-HT and LH in low-frequency EA-treated rats were higher than all the other groups. These results indicate that compared to high-frequency EA, the low-frequency EA might be efficacious in the treatment of premature ejaculation, thereby improving sexual behavior.
  4,773 483 4
Sex-related differences in sudomotor function in healthy early twenties focused on activated sweat gland density
Tae-Hwan Park, Jeong-Beom Lee, Hye-Jin Lee, Bahda Yun
January-February 2020, 63(1):1-6
DOI:10.4103/CJP.CJP_46_19  PMID:32056980
The purpose of this study was to quantitatively assess the difference in sudomotor function between healthy males and females in their early twenties by measuring skin surface area and activated sweat gland density (ASGD). The quantitative sudomotor axon reflex test (QSART), a method for evaluating autonomic nervous system activity, was used for quantification. In QSART, the sweat glands are activated directly or indirectly by the subcutaneous application of neurotransmitters, such as acetylcholine, through iontophoresis. This series of mechanisms is called the sudomotor axon reflex. After recording age, height, weight, and several measurements of the forearm, QSART was performed on 101 healthy controls aged 21–26 years to measure ASGD. The mean temperature and humidity on the measurement days were 11.4°C and 58.1% on May 3, 2018, and 14.7°C and 70.3% on May 10, 2018. The result of independent sample t-test showed higher ASGD in women (P < 0.05). The body surface area and the surface area of the forearms were higher in men (P < 0.001), but the number of activated sweat glands was not significantly different according to sex. The activated sweat gland counts of the body and forearms were analyzed through linear regression by age for males and females. Except for the activated sweat gland count of the male body, the analysis showed a tendency to decrease with increasing age but was not statistically significant in any case (P > 0.05). Showing insufficient coefficient of determination (R2), multiple regression analyses with sex and ages did not correct this insignificance between age and activated sweat gland count.
  4,652 536 2
Muscle type from which satellite cells are derived plays a role in their damage response
Chuang-Yu Lin, Chun-Yin Hou, Chung-Min Tsai, Hsi Chang
May-June 2020, 63(3):113-121
DOI:10.4103/CJP.CJP_98_19  PMID:32594064
The aim of this study was to evaluate the response of satellite cells to muscular atrophies which possess different pathological characteristics and which were induced by distinct damages. Right lower limbs of rats were exposed to denervation or disuse and later its tibialis anterior (TA) or soleus (SOL) muscles were analyzed. After confirming their functional impairments indicated by common but distinct pathological and electrophysiological characteristics, the quantitative polymerase chain reaction analysis of Pax7 and Pax3 expressions and the number of Pax7+ve and Pax3+ve cells were analyzed sequentially at day 0, day 7, and day 14. TA muscles of both denervation- and disuse-induced atrophy models showed persisted low level of Pax7 expression from day 7 (0.91 ± 0.23 and 0.31 ± 0.07, P = 0.06, n = 6) through day 14 (1.09 ± 0.15 and 0.4 ± 0.09 [P < 0.05]). On the other hand, significant elevations were observed in Pax3 expression in both atrophy models (2.73 ± 0.46 and 2.75 ± 0.26 [P < 0.05]) at day 7. Similar to TA muscle, resembled pattern of Pax7 and Pax3 expression changes were observed between the SOL muscles of denervation- and disused-atrophy models. These trends were further confirmed by the changes in Pax7+ve and Pax3+ve cell numbers of TA and SOL muscles in both atrophy models. Despite the distinct pathological findings, similar patterns in the changes of Pax3 and Pax7 expressions and the changes of Pax7+ve and Pax3+ve cell numbers were observed between the denervation- and disuse-induced atrophy models and this commonality was admitted among the muscle type. Therefore, we claim that the muscle regeneration orchestrated by satellite cells was governed by the muscle type in which satellite cells reside.
  4,650 481 1