Surge of Sympathetic Activity during Hyperventilation at the End of Apnea for Patients with Obstructive Sleep Apnea.

Background and Objectives: The mechanisms connecting obstructive sleep apnea (OSA) and cardiovascular disease are multifactorial, involving intermittent hypoxia, hypercapnia, and sympathetic activation. The aim of this study was to explore the oscillations of sympathetic activity during the sleep apnea episodes throughout the entire night in patients with OSA. Materials and Methods: The participants received whole-night polysomnography (PSG), and electrocardiogram (EKG) data from the PSG were collected for heart rate variability (HRV) analysis. HRV measurements were conducted in the time and frequency domains. The root mean square of successive differences between normal heartbeats (RMSSD), which reflects parasympathetic activity, and the ratio of the absolute power of the low-frequency band (0.04-0.15 Hz) to the absolute power of the high-frequency band (0.015-0.4 Hz) (LF/HF ratio), which indicates sympathetic activity, were computed. Results: A total of 43 participants (35 men and 8 women) were included in the analysis. The mean age of the participants was 44.1 ± 11.3 years old, and the mean BMI was 28.6 ± 5.4 kg/m2. The sleep apnea episodes throughout the entire night in patients with OSA were selected randomly and occurred most frequently during the non-REM stages (39, 90.7%). The selected sleep apnea episodes typically exhibited multiple apneas, often interrupted by snoring respiration and followed by hyperventilation at the end of the episode (HE). Our findings indicate that the centers of the 5 min HRV window for the lowest and highest LF/HF ratios, at 111.8 ± 88.2 and 117.4 ± 88.6 min after sleep onset, respectively, showed a statistically significant difference (p < 0.001). Similarly, the ratios of the lowest and highest LF/HF, at 0.82 ± 0.56 and 3.53 ± 2.94, respectively, exhibited a statistically significant difference (p < 0.001). Conclusions: In the current study, the selected sleep apnea episodes throughout the entire night in patients with OSA occurred primarily during the non-REM stages. Additionally, we observed that sympathetic activity reached its peak in the window that includes hyperventilation at the end stage of apnea, potentially posing a cardiovascular risk. However, additional studies are needed to validate these results.

Oscillation of Sympathetic Activity in Patients with Obstructive Sleep Apnea during the First Hour of Sleep.

(1) Background: Snoring is a cardinal symptom of obstructive sleep apnea (OSA) and has been suggested to potentially increase sympathetic activity. On the other hand, sleep itself usually leads to a decrease in sympathetic activity. Heart rate variability (HRV) analysis is a non-invasive technique used to assess autonomic nervous system function. However, there is limited research on the combined impact of sleep and snoring on sympathetic activity in individuals with OSA, particularly during the first hour of sleep (non-rapid eye movement sleep). The current study aims to investigate the net effect of sleep and snoring on sympathetic activity and explore factors that might contribute to increased sympathetic activity in individuals with OSA during the first hour of sleep. (2) Methods: The participants were referred from the outpatient department for OSA diagnosis and underwent whole-night polysomnography (PSG). Electrocardiogram (EKG) data from the PSG were downloaded for HRV analysis. HRV measurements were conducted in both the time and frequency domain, including the root mean square of successive differences between normal heartbeats (RMSSD) and the ratio of the absolute power of the low-frequency (LF) band (0.04-0.15 Hz) to the absolute power of the high-frequency (HF) band (0.15-0.4 Hz) (LF/HF ratio), respectively. (3) Results: A total of 45 participants (38 men and 7 women) were included in the analysis. The RMSSD gradually increased from 0-5 min to 50-60 min (p = 0.024), while the LF/HF ratio decreased (p < 0.001) during the first hour of sleep (non-rapid eye movement sleep). The LF/HF ratios of the "S" (snoring) episodes were compared with those of the pre-S episodes. An elevated LF/HF ratio during the S episode was associated with the first snoring episode occurring more than 20 min after lying down to sleep (Odds ratio, OR = 10.9, p = 0.004) and with patients diagnosed with severe OSA (OR = 5.01, p = 0.045), as determined by logistic regression. (4) Conclusions: The study observed an increase in the value of RMSSD and a decrease in the value of the LF/HF ratio during the first hour of sleep for patients with OSA. Higher LF/HF ratios were associated with the first occurrence of snoring while lying down for more than 20 min and with patients with severe OSA.

Association of Heart Rate Variability with Obstructive Sleep Apnea in Adults.

Background and Objectives: Heart rate variability (HRV) analysis is a noninvasive method used to examine autonomic system function, and the clinical applications of HRV analysis have been well documented. The aim of this study is to investigate the association between HRV and the apnea-hypopnea index (AHI) in patients referred for polysomnography (PSG) for obstructive sleep apnea (OSA) diagnosis. Materials and Methods: Patients underwent whole-night PSG. Data on nocturnal HRV and AHI were analyzed. We determined the correlation of time- and frequency-domain parameters of HRV with the AHI. Results: A total of 62 participants (50 men and 12 women) were enrolled. The mean age, body mass index (BMI), neck circumference, and AHI score of the patients were 44.4 ± 11.5 years, 28.7 ± 5.2, 40.2 ± 4.8 cm, and 32.1 ± 27.0, respectively. The log root mean square of successive differences between normal heartbeats (RMSSD) were negatively correlated with BMI (p = 0.034) and neck circumference (p = 0.003). The log absolute power of the low-frequency band over high-frequency band (LF/HF) ratio was positively correlated with the AHI (p = 0.006). A higher log LF/HF power ratio (ß = 5.01, p = 0.029) and BMI (ß = 2.20, p < 0.001) were associated with a higher AHI value in multiple linear regression analysis. Conclusions: A higher log LF/HF power ratio and BMI were positively and significantly associated with the AHI during whole-night PSG in adult patients.

Snoring Index and Neck Circumference as Predictors of Adult Obstructive Sleep Apnea.

Background. Snoring is the cardinal symptom of obstructive sleep apnea (OSA). The acoustic features of snoring sounds include intra-snore (including snoring index [SI]) and inter-snore features. However, the correlation between snoring sounds and the severity of OSA according to the apnea−hypopnea index (AHI) is still unclear. We aimed to use the snoring index (SI) and the Epworth Sleepiness Scale (ESS) to predict OSA and its severity according to the AHI among middle-aged participants referred for polysomnography (PSG). Methods. In total, 50 participants (mean age, 47.5 ± 12.6 years; BMI: 29.2 ± 5.6 kg/m2) who reported snoring and were referred for a diagnosis of OSA and who underwent a whole night of PSG were recruited. Results. The mean AHI was 30.2 ± 27.2, and the mean SI was 87.9 ± 56.3 events/hour. Overall, 11 participants had daytime sleepiness (ESS > 10). The correlation between SI and AHI (r = 0.33, p = 0.021) was significant. Univariate linear regression analysis showed that male gender, body mass index, neck circumference, ESS, and SI were associated with AHI. SI (ß = 0.18, p = 0.004) and neck circumference (ß = 2.40, p < 0.001) remained significantly associated with AHI by the multivariate linear regression model. Conclusion. The total number of snores per hour of sleep and neck circumference were positively associated with OSA among adults referred for PSG.

Correlation between snoring sounds and obstructive sleep apnea in adults: a meta-regression analysis.

Objective: Snoring is a dominant clinical symptom in patients with obstructive sleep apnea (OSA), and analyzing snoring sounds might be a potential alternative to polysomnography (PSG) for the assessment of OSA. This study aimed to systematically examine the correlation between the snoring sounds and the apnea-hypopnea index (AHI) as the measures of OSA severity. Material and Methods: A comprehensive literature review using the MEDLINE, Embase, Cochrane Library, Scopus, and PubMed databases identified the published studies reporting the correlations between and severity of snoring and the AHI values by meta-regression analysis. Results: In total, 13 studies involving 3,153 adult patients were included in this study. The pooled correlation coefficient for snoring sounds and AHI values was 0.71 (95%CI: 0.49, 0.85) from the random-effects meta-analysis with the Knapp and Hartung adjustment. The I 2 and chi-square Q test demonstrated significant heterogeneity (97.6% and p<0.001). After adjusting for the effects of the other covariates, the mean value of the Fisher's r-to-z transformed correlation coefficient would have 0.80 less by the snoring rate (95%CI = -1.02, -0.57), 1.46 less by the snoring index (95%CI = -1.85, -1.07), and 0.21 less in the mean body mass index (95%CI = -0.31, -0.11), but 0.15 more in the mean age (95%CI = 0.10, 0.20). It fitted the data very well (R 2=0.9641). Conclusion: A high correlation between the severity of snoring and the AHI was found in the studies with PSG. As compared to the snoring rate and the snoring index, the snoring intensity, the snoring frequency, and the snoring time interval index were more sensitive measures for the severity of snoring.

Long-term benefits of a new oral appliance on adult snoring: a trend analysis.

Background: Snoring constitutes a worldwide public health concern that may be associated with daytime fatigue, endothelial dysfunction, vascular injury, stroke, cardiovascular diseases, and diabetes among female patients. This study explored the effects of the so-called Lin Oral Appliance (LOA) on Taiwanese adults' snoring rates. Methods: A time series analysis was conducted to examine the associations between LOAs' tongue compressors of different lengths, and snoring rates were calculated using the SnoreClock app. The LOA comprises 2 components: custom- made dental braces and tongue compressors of adjustable lengths; different versions had different-length compressors. Results: Our multiple linear regression time-series model revealed the effects of the LOA on snoring rates. The results indicated the following: i) LOA tongue compressor lengths of 1 and 2.5 cm (LOA-1 and LOA-2.5, respectively) were associated with reduced snoring rates; ii) sleep durations of 5.5-7.5 h and daytime sleepiness were associated with increased snoring rates; and iii) among participants with snoring rates above 10%, the snoring rates observed 1-7 days before a given day constituted a significant factor influencing snoring rates on the given day. Conclusions: We discovered that the LOA could reduce snoring rates and that the 2.5-cm compressor length in the LOA produced the best results.

Effects of a novel oral appliance on snoring in adults: A pilot study.

ABSTRACTBACKGROUND/PURPOSE: Oral appliances (OAs) have been recommended as alternatives for adult patients with obstructive sleep apnea who are intolerant of continuous positive airway pressure therapy. The aim of this study was to explore the effect on snoring rates among adult patients through use of a novel OA termed the Lin OA (LOA, airflow-interference-type nasal congestion relieving and snore-ceasing oral appliance). MATERIALS AND METHODS: The LOA consist of two parts: dental braces and a fixed tongue compressor. The compressor lengths range from 0.5 cm to 3.5 cm across versions. Patients used the LOA during sleep and the SnoreClock smartphone application recorded their snoring rates. RESULTS: A total of 4920 recordings (4239 recordings from 34 men, 681 recordings from 8 women) were used for the analysis. The recordings were sorted in accordance with the applied length of the LOA tongue compressor (0.5-3.5 cm, LOA-0.5, LOA-1 and LOA-3.5), and participants not using the LOA were denoted as the LOA-0 group. The women had higher snoring rates in the LOA-0, LOA-0.5 to LOA-2 groups, but lower snoring rates in the LOA-3 group than men by the univariate analysis. The snoring rates were significantly reduced by a mean of 5.04% with every 1 cm increase in tongue compressor length. Continuous LOA use resulted in snoring rate reductions of 0.02% per day by the random intercept model of the linear regression. CONCLUSION: Use of this novel LOA may significantly reduce snoring rates by 5.04% with each 1 cm increase in tongue compressor length.

Dependable algorithm for visualizing snoring duration through acoustic analysis: A pilot study.

Snoring is a nuisance for the bed partners of people who snore and is also associated with chronic diseases. Estimating the snoring duration from a whole-night sleep period is challenging. The authors present a dependable algorithm for visualizing snoring durations through acoustic analysis. Both instruments (Sony digital recorder and smartphone's SnoreClock app) were placed within 30 cm from the examinee's head during the sleep period. Subsequently, spectrograms were plotted based on audio files recorded from Sony recorders. The authors thereby developed an algorithm to validate snoring durations through visualization of typical snoring segments. In total, 37 snoring recordings obtained from 6 individuals were analyzed. The mean age of the participants was 44.6 ±â€…9.9 years. Every recorded file was tailored to a regular 600-second segment and plotted. Visualization revealed that the typical features of the clustered snores in the amplitude domains were near-isometric spikes (most had an ascending-descending trend). The recorded snores exhibited 1 or more visibly fixed frequency bands. Intervals were noted between the snoring clusters and were incorporated into the whole-night snoring calculation. The correlative coefficients of snoring rates from digitally recorded files examined between Examiners A and B were higher (0.865, P < .001) than those with SnoreClock app and Examiners (0.757, P < .001; 0.787, P < .001, respectively). A dependable algorithm with high reproducibility was developed for visualizing snoring durations.

Validation of snoring detection using a smartphone app.

PURPOSE: Snoring is closely related to obstructive sleep apnea in adults. The increasing abundance and availability of smartphone technology has facilitated the examination and monitoring of snoring at home through snoring apps. However, the accuracy of snoring detection by snoring apps is unclear. This study explored the snoring detection accuracy of Snore Clock-a paid snoring detection app for smartphones. METHODS: Snoring rates were detected by smartphones that had been installed with the paid app Snore Clock. The app provides information on the following variables: sleep duration, snoring duration, snoring loudness (in dB), maximum snoring loudness (in dB), and snoring duration rate (%). In brief, we first reviewed the snoring rates detected by Snore Clock; thereafter, an ear, nose, and throat specialist reviewed the actual snoring rates by using the playback of the app recordings. RESULTS: In total, the 201 snoring records of 11 patients were analyzed. Snoring rates measured by Snore Clock and those measured manually were closely correlated (r = 0.907). The mean snoring detection accuracy rate of Snore Clock was 95%, with a positive predictive value, negative predictive value, sensitivity, and specificity of 65% ± 35%, 97% ± 4%, 78% ± 25%, and 97% ± 4%, respectively. However, the higher the snoring rates, the higher were the false-negative rates for the app. CONCLUSION: Snore Clock is compatible with various brands of smartphones and has a high predictive value for snoring. Based on the strong correlation between Snore Clock and manual approaches for snoring detection, these findings have validated that Snore Clock has the capacity for at-home snoring detection.

Plate osteosynthesis of single metacarpal fracture: WALANT technique is a cost-effective approach to reduce postoperative pain and discomfort in contrast to general anesthesia and wrist block.

BACKGROUND: The WALANT (wide-awake local anesthesia with no tourniquet) technique was based on local infiltration of lidocaine and epinephrine. This technique has rapidly gained popularity in recent years and can perform most hand operations. This study aimed to investigate the time spent on anesthesia and operation and perform an economic analysis among general anesthesia, wrist block with a tourniquet, and the WALANT technique for the internal fixation of metacarpal fractures. METHODS: We retrospectively reviewed all the single metacarpal fractures managed with the same procedure, open reduction, and internal fixation with the plate between January 2015 and December 2019. They were divided into three groups according to the method of anesthesia: (1) general anesthesia (GA group), (2) wrist block with a tourniquet (WB group), and (3) WALANT technique (WALANT group). We collected and analyzed patient demographic data, perioperative or postoperative complications, number of hospital days, and postoperative functional recovery assessment. RESULTS: A total of 63 patients met the inclusion criteria, including 24 in the GA group, 28 in the wrist block group using a tourniquet, and 11 in the WALANT group. There were no complications during the operation and follow-up in each group. The GA group had an average of 32.8 min of anesthesia time, significantly longer than the other two groups. However, there is no significant difference regarding surgical time among the presenting three groups. The discomfort of vomiting and nausea after surgery occurred in 20 patients in the GA group (38.1%). Nevertheless, there was no postoperative vomiting and nausea present in both the WB and WALANT groups. Most patients achieved full recovery of pre-injury interphalangeal and metacarpophalangeal motion at the final assessment of functional recovery. CONCLUSIONS: The patients undergoing metacarpal fixation surgery under WALANT or WB had significantly less anesthesia time and postoperative vomiting and nausea. Moreover, there was no difference in surgical time and intraoperative complications. The time-related reduction improved the utilization of the operation room for additional cases. The reduction of the preoperative examination, anesthesia fee, postoperative recovery room observation, and hospitalization can effectively reduce medical costs. Furthermore, the WALANT group is more acceptable because of no tourniquet, which commonly causes discomfort.

Metabolomics profiling of haloperidol and validation of thromboxane-related signaling in the early development of zebrafish.

Haloperidol is a common butyrophenone-derivative antipsychotic drug that is used clinically to treat schizophrenia and to control Tourette disorder. Haloperidol has been shown to be an embryonic toxicant and to cause a variety of adverse effects that affect human embryonic development. However, the pathway impaired by haloperidol during the developmental stages remains unclear. To elucidate the innate toxicological pathway of haloperidol, we investigated the lethality of haloperidol during the embryonic development of zebrafish. We observed that haloperidol caused serious morphological changes, with an LD50 of 9.7 x 10-6 ± 2.4 x 10-6 µg/L. Next, we established a systematic approach to perform metabolite profiling in embryonic zebrafish with various concentrations of haloperidol and analyzed the metabolites using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). A total of 304 metabolites were identified and 86 metabolites were chosen to predict potential pathways. Among the metabolites, we found through prediction that numerous metabolomics-biological pathways are associated with haloperidol, including peroxisome-proliferator-activated receptor (ppar), thromboxane, and mTOR signaling. Quantitative real time-qPCR was then used to validate the gene expression potentially associated with the thromboxane, which is a metabolic product of arachidonic acid and considered to be important for cell proliferation and the inflammatory response. To sum up, analysis of metabolites in the zebrafish model provides a system for mining biomarkers that reflect biological significance and highlight the therapeutic potency in humans. In addition, it may show potential for application to other pharmaceuticals to identify their various activities and clarify functional mechanisms in the future.

Fucoidan⁻Fucoxanthin Ameliorated Cardiac Function via IRS1/GRB2/ SOS1, GSK3ß/CREB Pathways and Metabolic Pathways in Senescent Mice.

The effects of low molecular weight fucoidan (LMWF) in combination with high-stability fucoxanthin (HSFUCO) on cardiac function and the metabolic pathways of aging mice (Mus musculus) were investigated. We demonstrated that LMWF and HSFUCO could improve cardiac function in aging mice. Aging mice were treated with LMWF and HSFUCO, either on their own or in combination, on 28 consecutive days. Electrocardiography and whole-cell patch-clamp were used to measure QT interval and action potential duration (APD) of the subjects. Cardiac tissue morphology, reactive oxygen species, and Western blot were also applied. Ultra-high-performance liquid chromatography⁻quadrupole time-of-flight (UPLC-QTOF) mass spectrometry was used for investigating metabolic alterations. The use of LMWF and HSFUCO resulted in improvements in both ventricular rhythms (QT and APD). Treatment with fucoidan and fucoxanthin reduced the expression levels of SOS1 and GRB2 while increasing GSK3ß, CREB and IRS1 proteins expression in the aging process. Three main metabolic pathways, namely the TCA cycle, glycolysis, and steroid hormone biosynthesis, were highly enriched in the pathway enrichment analysis. When taken together, the LMWF and HSFUCO treatment improved both the ventricular rhythm and the muscular function of aging subjects by interfering with the metabolism and gene function.

Spontaneously hypertensive rats exhibit higher sensitivity to ethanol-induced hypotensive effects: Role of NMDA receptors and nitric oxide in rostral ventrolateral medulla.

Intake of ethanol (alcohol) affects cardiovascular function. Acute ethanol intake has been shown to lower blood pressure (BP) in hypertensive patients. The present study was undertaken to examine the effects and mechanisms of acute administration of ethanol on BP in hypertensive and normotensive rats. Ethanol was given by intraperitoneal (i.p.) injection in male spontaneously hypertensive rats (SHRs) and the normotensive Wistar-Kyoto rats (WKYs). BP responses were measured in free-moving conscious rats or in urethane-anesthetized rats. Inhibitors were applied by bilateral microinjection into the rostral ventrolateral medulla (RVLM). Nitric oxide (NO•) levels and glutamate levels were determined by nitrate and nitrite (NOx) analyzer and HPLC-ECD, respectively. Intraperitoneal (i.p.) injection of ethanol (1.6 g/kg) caused a significant decrease in BP in free-moving or in anesthetized SHRs but not in WKYs. A higher dose (3.2 g/kg) of ethanol decreased BP in both SHRs and WKYs, although the depressor responses in SHRs occurred significantly earlier than those in WKYs. The blood ethanol concentrations 60 min after injection were similar in SHRs and WKYs. Bilateral microinjection of nitric oxide synthase (NOS) inhibitors or glutamatergic NMDA receptor antagonists into the RVLM 5 min after administration of ethanol significantly inhibited the ethanol-induced depressor effects in SHRs. The levels of NOx and glutamate release in the RVLM following ethanol administration and the NOx content in the RVLM areas 30 min after administration were significantly increased in SHRs, but not in WKYs. Our results showed that SHRs were more sensitive to ethanol-induced hypotensive effects than WKYs because of augmentation of ethanol-induced expression of the glutamatergic NMDA receptor/NO• signal in the RVLM of SHRs.

PM2.5 induced cardiac hypertrophy via CREB/GSK3b/SOS1 pathway and metabolomics alterations.

The particle matter with diameter less 2.5µm (PM2.5) easier to adsorb toxic substance, and interfere with pulmonary gas exchange. In this study, cardioprotective effects of low molecular weight (LMW) fucoidan in cardiac hypertrophy subjects induced by PM2.5 exposure was conducted by measuring QT interval, Blood pressure, cardiac structure, metabolites and proteins expression in different organs. After PM2.5 exposure, increase in blood pressure, abnormal cardiac function (Prolongation of Action Potential Duration and QT Interval), and structral remodeling (cardiac hypertrophy and fibrosis) were recorded. Fucoidan supplement in consecutive 28 days can reduce the damage to myocardial injury caused by PM2.5. Clearance effect of fucoidan in serum, heart, kidney, lung and liver was found due to organic and inorganic compounds reduced SOS1, CREB, GSK3b, and GRB2 protein level were changed under PM2.5 exposure. Whereas, only CREB level was reduced after fucoidan treatment. Metabolic alteration was also determined that PM2.5 severely damage cardiac tissue and compromise its function. After treatment with fucoidan, the cardiac function was significantly recovered. Our finding demonstrated that LMW could enhance the cardiac status of mice with PM2.5 exposures by rescued QT interval prolongation, action potential and cardiac hypertrophy, and cardiac fibrosis decline.

Arsenic induces cardiac rhythm dysfunction and acylcarnitines metabolism perturbation in rats.

BACKGROUND: Arsenic has been shown to cause various diseases (such as blackfoot disease, cardiovascular diseases, bladder cancer and skin cancer) in many areas of the world. However, the effects of arsenic on cardiac rhythm functions still lack investigation. METHODS: In this study, different concentrations of arsenic were orally applied to Sprague Dawley rats in order to examine the relationship between arsenic and cardiovascular rhythm (i.e. long QT) via electrocardiography measurement. In addition, QT correction formulas were used to correct the QT interval. Linear regression analysis was used to examine the correlation between the QT interval and cardiac cycle length, corrected QT and heart rate. A metabolomic approach was applied to study carnitine-derived metabolites under arsenic exposure by using an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) system. RESULTS: The present findings showed that exposure to arsenic causes QT and corrected (QTc) prolongation and heart rate declines. However, the linear correlation analysis showed that there is no significant correlation between cardiac cycle length and the QT interval in both the uncorrected QT and corrected QT. The expression of acylcarnitine metabolites can be used to discriminate the control and arsenic-treated groups. CONCLUSIONS: This study provides information concerning the effect of arsenic at different concentrations on cardiac rhythm (such as QT, QTc, and heart rate) but not on cardiac cycle length. The metabolism of acylcarnitine metabolites can be a potential pathway for arsenic-induced cardiac rhythm dysfunction in rats.

Highly efficient adsorption of dyes by biochar derived from pigments-extracted macroalgae pyrolyzed at different temperature.

Biochar is known to efficiently adsorb dyes from wastewater. In this study, biochar was derived from macroalgae residue by pyrolysis, and the influence of varying temperature (from 400 °C to 800 °C) on biochar characteristics was investigated. Among the biochar samples tested, macroalgae-derived biochar possessing highly porous structure, special surface chemical behavior and high thermal stability was found to be efficient in removing malachite green, crystal violet and Congo red. The biochar derived by pyrolysis at 800 °C showed the highest adsorption capacity for malachite green (5306.2 mg g-1). In this study, the transformation of microalgae residue into a highly efficient dye adsorbent is a promising procedure for economic and environmental protection.

Metabolomic assessment of arsenite toxicity and novel biomarker discovery in early development of zebrafish embryos.

CONTEXT: Arsenic poisoning commonly occurs through exposure to water contaminated with arsenic and causes long-term symptoms. Of all the arsenic derivatives, arsenite is the one of the most toxic compounds. However, the toxicity of arsenite during developmental stages is still unclear. OBJECTIVE: In this study, we performed a metabolomic analysis of arsenite responses in embryonic zebrafish. MATERIALS AND METHODS: Embryonic zebrafish were used as an animal model in this study. They were exposed to sodium arsenite under different concentrations (0.5, 1.0, 2.0, and 5.0 mg/L) in 24 h, 48 h and 72 h post fertilization. Changes in morphology were observed through a light microscope. Changes in metabolomics were identified using an ultraperformance liquid chromatography quadrupole time-of-flight system. RESULTS: The IC50 range was 0.75 ±â€¯0.25 mg/L. Compared with the control group, the embryonic lethality rate decreased to 33.3% under 1.0 mg/L of arsenite treatment, whereas it decreased to 20.0% under 2.0 mg/L of arsenite treatment. Numerous body axis curvatures were also observed under treatment with 2.0 and 5.0 mg/L of arsenic. Pericardium and yolk sac edema were randomly discovered and found to worsen over time. Moreover, the 10 metabolites with the highest variable importance in projection score were identified as potential biomarkers for arsenic exposure. CONCLUSION: Arsenic exposure not only leads to a change in the morphology of embryonic zebrafish but also disturbs the metabolism of zebrafish in early developmental stages.

Distinct expression of CDCA3, CDCA5, and CDCA8 leads to shorter relapse free survival in breast cancer patient.

Breast cancer is a dangerous disease that results in high mortality rates for cancer patients. Many methods have been developed for the treatment and prevention of this disease. Determining the expression patterns of certain target genes in specific subtypes of breast cancer is important for developing new therapies for breast cancer. In the present study, we performed a holistic approach to screening the mRNA expression of six members of the cell division cycle-associated gene family (CDCA) with a focus on breast cancer using the Oncomine and The Cancer Cell Line Encyclopedia (CCLE) databases. Furthermore, Gene Expression-Based Outcome for Breast Cancer Online (GOBO) was also used to deeply mine the expression of each CDCA gene in clinical breast cancer tissue and breast cancer cell lines. Finally, the mRNA expression of the CDCA genes as related to breast cancer patient survival were analyzed using a Kaplan-Meier plot. CDCA3, CDCA5, and CDCA8 mRNA expression levels were significantly higher than the control sample in both clinical tumor sample and cancer cell lines. These highly expressed genes in the tumors of breast cancer patients dramatically reduced patient survival. The interaction network of CDCA3, CDCA5, and CDCA8 with their co-expressed genes also revealed that CDCA3 expression was highly correlated with cell cycle related genes such as CCNB2, CDC20, CDKN3, and CCNB1. CDCA5 expression was correlated with BUB1 and TRIP13, while CDCA8 expression was correlated with BUB1 and CCNB1. Altogether, these findings suggested CDCA3, CDCA5, and CDCA8 could have a high potency as targeted breast cancer therapies.

Zebrafish: A Premier Vertebrate Model for Biomedical Research in Indian Scenario.

The zebrafish (Danio rerio) is a versatile model organism that has been used in biomedical research for several decades to study a wide range of biological phenomena. There are many technical advantages of using zebrafish over other vertebrate models. They are readily available, hardy, easy, and inexpensive to maintain in the laboratory, have a short life cycle, and have excellent fecundity. Due to its optical clarity and reproducible capabilities, it has become one of the predominant models of human genetic diseases. Zebrafish research has made rapid strides in the United States and Europe, but in India the field is at an early stage and many researchers still remain unaware of the full research potential of this tiny fish. The zebrafish model system was introduced into India in the early 2000s. Up to now, more than 200 scientific referred articles have been published by Indian researchers. This review gives an overview of the current state of knowledge for zebrafish research in India, with the aim of promoting wider utilization of zebrafish for high level biological studies.

Voltage-gated calcium channels: Novel targets for cancer therapy.

Voltage-gated calcium channels (VGCCs) comprise five subtypes: The L-type; R-type; N-type; P/Q-type; and T-type, which are encoded by α1 subunit genes. Calcium ion channels also have confirmed roles in cellular functions, including mitogenesis, proliferation, differentiation, apoptosis and metastasis. An association between VGCCs, a reduction in proliferation and an increase in apoptosis in prostate cancer cells has also been reported. Therefore, in the present study, the online clinical database Oncomine was used to identify the alterations in the mRNA expression level of VGCCs in 19 cancer subtypes. Overall, VGCC family genes exhibited under-expression in numerous types of cancer, including brain, breast, kidney and lung cancers. Notably, the majority of VGCC family members (CACNA1C, CACNA1D, CACNA1A, CACNA1B, CACNA1E, CACNA1H and CACNA1I) exhibited low expression in brain tumors, with mRNA expression levels in the top 1-9% of downregulated gene rankings. A total of 5 VGCC family members (CACNA1A, CACNA1B, CACNA1E, CACNA1G and CACNA1I) were under-expressed in breast cancer, with a gene ranking in the top 1-10% of the low-expressed genes compared with normal tissue. In kidney and lung cancers, CACNA1S, CACNA1C, CACNA1D, CACNA1A and CACNA1H exhibited low expression, with gene rankings in the top 1-8% of downregulated genes. In conclusion, the present findings may contribute to the development of new cancer treatment approaches by identifying target genes involved in specific types of cancer.