Effects of manual therapy combined with therapeutic exercise versus routine physical therapy on brain biomarkers in patients with chronic non-specific neck pain in Thailand: a study protocol for a single-blinded randomised controlled trial.

INTRODUCTION: Structural brain alterations in pain-related areas have been demonstrated in patients with non-specific neck pain. While manual therapy combined with therapeutic exercise is an effective management for neck pain, its underlying mechanisms are poorly understood. The primary objective of this trial is to investigate the effects of manual therapy combined with therapeutic exercise on grey matter volume and thickness in patients with chronic non-specific neck pain. The secondary objectives are to assess changes in white matter integrity, neurochemical biomarkers, clinical features of neck pain, cervical range of motion and cervical muscle strength. METHODS AND ANALYSIS: This study is a single-blinded, randomised controlled trial. Fifty-two participants with chronic non-specific neck pain will be recruited into the study. Participants will be randomly allocated to either an intervention or control group (1:1 ratio). Participants in the intervention group will receive manual therapy combined with therapeutic exercise for 10 weeks (two visits per week). The control group will receive routine physical therapy. Primary outcomes are whole-brain and regional grey matter volume and thickness. Secondary outcomes are white matter integrity (fractional anisotropy and mean diffusivity), neurochemical biomarkers (N-acetylaspartate, creatine, glutamate/glutamine, myoinositol and choline), clinical features (neck pain intensity, duration, neck disability and psychological symptoms), cervical range of motion and cervical muscle strength. All outcome measures will be taken at baseline and postintervention. ETHICS AND DISSEMINATION: Ethical approval of this study has been granted by Faculty of Associated Medical Science, Chiang Mai University. The results of this trial will be disseminated through a peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT05568394.

Effects of low-dose radiation on human blood components after in vitro exposure to gamma radiation from 137Cs radioactivity.

This current study was designed to determine the effects of in vitro exposure to radioactive cesium-137 on human blood components. Whole blood samples were given a radiation dose of 0.02, 0.05, 0.1, 0.2, and 0.3 mGy of gamma radiation using a 137Cs radioactive standard source. The whole blood samples that were exposed to 0 mGy served as sham-controls. The spectrofluoroscopic technique was used to determine the autofluorescence spectrum of protein in plasma or red blood cells by using excitation wavelength and range of emission wavelengths at 280 nm and 300-550 nm, respectively. The hemolysis of red blood cells was evaluated by determination of the release of hemoglobin from the red blood cells to the supernatant. Complete blood counts were also determined in whole blood. The results showed that there was no change in the ratio of fluorescence emission intensity at 340 nm of wavelength of protein extract from irradiated whole blood or red blood cells compared to the corresponding non-irradiated control. The hemolysis value did not change in irradiated whole blood when compared to the corresponding non-irradiated group. In addition, complete blood count values in irradiated groups did not differ from non-irradiated group. These current results suggested that there were no harmful effects of the low-dose gamma radiation from radioactive 137Cs on blood components when human whole blood was exposed to gamma radiation in an in vitro condition.

Modulation of p-glycoprotein-mediated efflux pirarubicin in living multidrug-resistant K562/Dox cell lines by 4-hydroxybenzoic acid and 4-hydroxy-3-methoxybenzoic acid via impairment of the cellular energetic state.

The objective was to investigate the effect of 4-hydroxybenzoic acid (4-HBA) and 4-hydroxy-3-methoxybenzoic acid (Vanillic acid, VA) on p-glycoprotein (P-gp) activity in multidrug-resistant K562/Dox cancer cells. The cytotoxic and co-treatment with pirarubicin (Pira) were analyzed using a resazurin assay. A noninvasive functional spectrofluorometric technique was used to determine the kinetics of Pira uptake in living multidrug-resistant K562/Dox cancer cells. The three biological endpoints for determination of cellular energetic state included the activity of mitochondria, mitochondrial membrane potential (ΔΨm), and ATP levels. The results revealed that 4-HBA (10 mM) and VA (5 and 10 mM) statistically decreased cell viability in K562 and multidrug-resistant K562/Dox cancer cells. In ways consistent with that result, 4-HBA and VA (0.01, 0.1, 1, and 10 mM) could statistically decrease the IC50 of Pira in K562 and multidrug-resistant K562/Dox cancer cells at 48 and 72 h. The overall intracellular Pira concentration increased in 4-HBA- and VA-treated multidrug-resistant K562/Dox cancer cells when compared to control. The ratio of ka i/ka 0 in 4-HBA- and VA-treated multidrug-resistant K562/Dox cancer cells was significantly decreased when 4-HBA and VA concentration increased. The activity of mitochondria, ΔΨm, and ATP levels significantly reduced in multidrug-resistant K562/Dox cancer cells incubated with 0.01, 0.1, 1, and 10 mM 4-HBA and VA at all harvest time points. In conclusion, 4-HBA and VA were able to bring about cell death in multidrug-resistant K562/Dox cancer cell at high concentrations. The 4-HBA and VA could modify P-gp function via an impaired cellular energetic state, resulting in increased in intracellular drug concentration in multidrug-resistant K562/Dox cancer cells.

Effect of pre-low-dose irradiation on anticancer activities of gallic acid in leukemic K562 and K562/Dox cells: cell viability and cellular energetic state studies.

The aim of this study was to determine the effects of pre-low-dose irradiation followed by gallic acid (GA) on cell viability and cellular energetic state of leukemic K562 and K562/Dox cells. The cells were irradiated with 0.02, 0.05, and 0.1 Gy of X-rays. For determining cell viability, pre-low-dose irradiation was followed by 10 or 100 µM GA at 24 h post-irradiation, and the cell viability was then determined at 48 h post-irradiation. For cellular energetic state, pre-low-dose irradiation was followed by 10 or 100 µM GA at 1.5 h post-irradiation and the mitochondrial activity, mitochondrial membrane potential (ΔΨm), and ATP level were determined at 3 h post-irradiation. The % cell viability was significantly decreased in both cells that were irradiated with X-rays followed by treatment with 10 or 100 µM GA at 24 h post-irradiation, when compared with control group. However, this did not happen when compared with GA alone without any pre-low-dose irradiation. The mitochondrial activity had significantly decreased in 10 µM GA-treated K562 cells and the mitochondrial activity, ΔΨm, and ATP levels had significantly decreased in 10 µM GA-treated K562/Dox cells after irradiation to X-rays when compared with GA alone group. In addition, the ΔΨm and ATP levels was significantly decreased in only 100 µM GA-treated K562/Dox cells, but was not decreased in 100 µM GA-treated K562 cells after exposure to X-rays. These findings suggest that pre-low-dose irradiation followed by GA could not kill K562 and K562/Dox cells, but could improve cellular energetic damage of GA effects possibly through mitochondrial impairment.

Noninvasive NMR/MRS Metabolic Parameters to Evaluate Metabolic Syndrome in Rats.

(1) Background: Ectopic fat deposition and its effects, metabolic syndrome, have been significantly correlated to lifestyle and caloric consumption. There is no specific noninvasive evaluation tool being used in order to establish clinical markers for tracing the metabolic pathway implicated in obesity-related abnormalities that occur in the body as a result of a high-fat diet (HFD). The purpose of this work is to investigate in vivo ectopic fat distribution and in vitro metabolite profiles given by HFDs, as well as how they are inter-related, in order to find surrogate metabolic biomarkers in the development of metabolic syndrome utilizing noninvasive approaches. (2) Methods: Male Wistar rats were divided into a standard normal chow diet, ND group, and HFD group. After 16 weeks of different diet administration, blood samples were collected for proton nuclear magnetic resonance (1H NMR) and biochemical analysis. Magnetic resonance imaging/proton magnetic resonance spectroscopy (MRI/1H MRS) was performed on the abdomen, liver, and psoas muscle of the rats. (3) Results: Visceral fat showed the strongest relationship with blood cholesterol. Although liver fat content (LFC) was not associated with any biophysical profiles, it had the highest correlation with metabolites such as (-CH2)n very-low-density lipoprotein/low-density lipoprotein (VLDL/LDL), lactate, and N-acetyl glycoprotein of serum 1H NMR. HFD showed no obvious influence on muscle fat accumulation. Acetoacetate, N-acetyl glycoprotein, lactate, (-CH2)n VLDL/LDL, and valine were the five possible metabolic biomarkers used to differentiate HFD from ND in the present study. (4) Conclusions: Our study has validated the influence of long-term HFD-induced ectopic fat on body metabolism as well as the metabolic profile deterioration both in vivo and in vitro.

The Incidence and Associated Risk Factors of Contrast-Induced Nephropathy after Contrast-Enhanced Computed Tomography in the Emergency Setting: A Systematic Review.

Iodinated contrast media (ICM) during contrast-enhanced computed tomography (CECT) in the emergency department (ED) is essential to diagnose acute conditions, despite risks of contrast-induced nephropathy (CIN) development and its associated complications. This systematic review aims to evaluate the incidence of CIN and CIN-induced complications, and to explore the relevance of classical risk factors for CIN among ED patients receiving ICM. PubMed, Cochrane, and Web of Science were used on 30 August 2021 to search for peer-reviewed English articles reporting on CIN incidence among ED patients aged ≥18 years who underwent an intravenous CECT. The inclusion criteria included studies that were in English, peer-reviewed, and involved ED patients aged ≥18 years who underwent single intravenous CECT. Studies on intra-arterial procedures and preventive strategies, meta-analyses, clinical guidelines, review articles, and case reports were excluded. The JBI critical appraisal checklist was applied to assess the risk of bias. In total, 18 studies were included wherein 15 were retrospective studies while three were prospective studies. We found a relatively higher CIN incidence in the ED, with variations owing to the CIN definitions. Several classical risk factors including acute hypotension remain linked to CIN onset in ED settings unlike factors such as age and diabetes. While risk of adverse renal events due to CIN is low, there is higher risk of CIN-induced mortality in the ED. Therefore, with the higher incidence of CIN and CIN-induced mortality rates in the ED, ICM administration during CECT in the ED should still be clinically justified after assessing both benefits and risks.

Effect of iodinated radiographic contrast media on radioimmunoassay for measuring thyroid hormones.

Radioimmunoassay (RIA) is one of the most routine laboratory tests for diagnosing thyroid disease. Patients might receive iodine in the form of intravenous iodinated radiographic contrast media (IRCM) before testing of serum thyroxin (T4) or triiodothyronine (T3) concentration by RIA. The objective was to determine the effect of IRCM on T4 and T3 hormone tests in normal, hypothyroid, and hyperthyroid hormone conditions by RIA. IRCMs (0, 2.5, 5 and 10 mgI/mL) used in this study were iopromide and iodixanol. RIA was determined by commercial T4 RIA kit and T3 RIA kits. The method suggested by the manufacturer was followed. Normal, hypothyroid, and hyperthyroid hormones condition were 1.2 ng/mL, 0.2 ng/mL and 2.2 ng/mL for T3 hormone concentration and 70 ng/mL, 30 ng/mL and 140 ng/mL for T4 hormone concentration, respectively. %Bound values were compared between IRCM-incubated groups and non-incubated group. The data showed that iopromide-incubated groups did not statistically significant change %bound values of T3 and T4 hormone tests in normal, hypothyroid, and hyperthyroid conditions, compared to the non-incubated group. In the same way, %bound values of T3 and T4 hormone tests in iodixanol-incubated groups did not change at all conditions when compared to the non-incubated group. This finding suggested that iodinated radiographic contrast media was unlikely to result in significant problems with radioimmunoassay for measuring T3 and T4 thyroid hormones.

Dysfunction of insulin-AKT-UCP1 signalling inhibits transdifferentiation of human and mouse white preadipocytes into brown-like adipocytes.

The mechanism of insulin signaling on browning of white preadipocytes remains unclear. Human and mouse primary subcutaneous white preadipocytes (hsASCs and WT lean and obese msASCs, respectively) were induced to transdifferentiate into beige adipocytes under conditions of intact or blocked insulin signaling, respectively. Level of phosphoinositide-3-kinase (PI3K) after induction of beige adipocytes under conditions of normal insulin signaling, phosphorylated protein kinase B (pAKT), peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α), zinc-fifinger transcriptional factor PRD1-BF1-RIZ1 homologous domain-containing protein 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein beta (C/EBPß) were significantly increased. Conversely, when insulin signaling is incompletely inhibited, the expression of the thermogenic and adipogenic factors is significantly reduced, with obvious impairment of adipogenesis. However, phosphorylation level of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and expression level of sirtuin type 1 (SIRT1) had increased. These white preadipocytes from different donors showed similar dynamic change in morphology and molecular levels during the browning. The present data indicate that insulin signaling plays a important role in regulation of browning of hsASCs and msASCs through PI3K-AKT-UCP1 signaling pathway. The insulin-AMPK-SIRT1 pathway was also involved in the adipocytes browning, while its effect is limited.

Advanced Molecular Imaging (MRI/MRS/1H NMR) for Metabolic Information in Young Adults with Health Risk Obesity.

BACKGROUND: Obesity or being overweight is a medical condition of abnormal body fat accumulation which is associated with a higher risk of developing metabolic syndrome. The distinct body fat depots on specific parts of the anatomy have unique metabolic properties and different types of regional excessive fat distribution can be a disease hazard. The aim of this study was to identify the metabolome and molecular imaging phenotypes among a young adult population. METHODS: The amount and distribution of fat and lipid metabolites profile in the abdomen, liver, and calf muscles of 46 normal weight, 17 overweight, and 13 obese participants were acquired using MRI and MR spectroscopy (MRS), respectively. The serum metabolic profile was obtained using proton NMR spectroscopy. NMR spectra were integrated into seven integration regions, which reflect relative metabolites. RESULTS: A significant metabolic disorder symptom appeared in the overweight and obese group, and increased lipid deposition occurred in the abdomen, hepatocytes, and muscles that were statistically significant. Overall, the visceral fat depots had a marked influence on dyslipidemia biomarkers, blood triglyceride (r = 0.592, p < 0.001), and high-density lipoprotein cholesterol (r = -0.484, p < 0.001). Intrahepatocellular lipid was associated with diabetes predictors for hemoglobin (HbA1c%; r = 0.379, p < 0.001) and for fasting blood sugar (r = 0.333, p < 0.05). The lipid signals in serum triglyceride and glucose signals gave similar correspondence to biochemical lipid profiles. CONCLUSIONS: This study proves the association between alteration in metabolome in young adults, which is the key population for early prevention of obesity and metabolic syndrome. This study suggests that dyslipidemia prevalence is influenced mainly by the visceral fat depot, and liver fat depot is a key determinant for glucose metabolism and hyperglycemia. Moreover, noninvasive advanced molecular imaging completely elucidated the impact of fat distribution on the anthropometric and laboratory parameters, especially indices of the metabolic syndrome biomarkers in young adults.

Gallic acid enhances pirarubicin­induced anticancer in living K562 and K562/Dox leukemia cancer cells through cellular energetic state impairment and P­glycoprotein inhibition.

Leukemia is a common malignancy affecting humans worldwide. Pirarubicin (Pira) is one of the anticancer agents used for the treatment of leukemia. Although Pira is effective, drug resistance may develop in cancer cells exposed to this drug, whereas the combination of natural products with Pira may help to overcome this problem. The aim of the present study was to focus on the effect of gallic acid (GA) on the anticancer activity of Pira in K562 leukemia cells and K562/doxorubicin (Dox)­resistant leukemia cells in order to investigate the possible underlying mechanisms. The cell viability, mitochondrial activity, mitochondrial membrane potential (ΔΨm) and ATP levels were assessed in living K562 and K562/Dox cancer cells following treatment with GA/Pira combination, GA alone or Pira alone. P­glycoprotein­mediated efflux of Pira was determined in GA­treated K562/Dox cancer cells. The results demonstrated that GA/Pira combination decreased cell viability, mitochondrial activity, ΔΨm and ATP levels in K562 and K562/Dox cancer cells in a GA concentration­dependent manner compared with non­treated or Pira­treated cells. GA inhibited P­glycoprotein­mediated efflux of Pira in GA­treated K562/Dox cancer cells. Therefore, GA enhanced the anticancer effect of Pira on K562 and K562/Dox cancer cells through cellular energy status impairment, and was able to reverse drug resistance in living K562/Dox cancer cells by inhibiting the function of P­glycoprotein.

Waist Circumference and BMI Are Strongly Correlated with MRI-Derived Fat Compartments in Young Adults.

Young adulthood is increasingly considered as a vulnerable age group for significant weight gain, and it is apparent that there is an increasing number of new cases of metabolic syndrome developing among this population. This study included 60 young adult volunteers (18-26 years old). All participants obtained a calculated total abdominal fat percentage, subcutaneous fat percentage, and visceral fat percentage using a semiautomatic segmentation technique from T1-weighted magnetic resonance imaging (MRI) images of the abdomen. The results show strongest correlation between abdominal fat and BMI (r = 0.824) followed by subcutaneous fat (r = 0.768), and visceral fat (r = 0.633) respectively, (p < 0.001 for all, after having been adjusted for age and gender). Among anthropometric measurements, waist circumference showed strong correlation with all fat compartments (r = 0.737 for abdominal, r = 0.707 for subcutaneous fat, and r = 0.512 for visceral fat; p < 0.001 for all). The results obtained from examining the blood revealed that there was a moderate positive correlation relationship between all fat compartments with triglyceride, high-density lipoprotein, and fasting glucose levels (p < 0.05 for all). This study suggests that both BMI and waist circumference could be used to assess the fat compartments and treatment targets to reduce the risk of metabolic disorders and health risks in the young adult population.

Identification of Metabolic Phenotypes in Young Adults with Obesity by 1H NMR Metabolomics of Blood Serum.

(1) Since the obesity prevalence rate has been consistently increasing, it is necessary to find an effective way to prevent and treat it. Although progress is being made to reduce obesity in the young adult population, a better understanding of obesity-related metabolomics and related biochemical mechanisms is urgently needed for developing appropriate screening strategies. Therefore, the aim of this study is to identify the serum metabolic profile associated with young adult obesity and its metabolic phenotypes. (2) Methods: The serum metabolic profile of 30 obese and 30 normal-weight young adults was obtained using proton nuclear magnetic resonance spectroscopy (1H NMR). 1H NMR spectra were integrated into 24 integration regions, which reflect relative metabolites, and were used as statistical variables. (3) Results: The obese group showed increased levels of lipids, glucose, glutamate, N-acetyl glycoprotein, alanine, lactate, 3 hydroxybutyrate and branch chain amino acid (BCAA), and decreased levels of choline as compared with the normal-weight group. Non-hyperlipidemia obese adults showed lower levels of lipids and lactate, glutamate, acetoacetate, N-acetyl glycoprotein, isoleucine, and higher levels of choline and glutamine, as compared with hyperlipidemic obese adults. (4) Conclusions: This study reveals valuable findings in the field of metabolomics and young adult obesity. We propose several serum biomarkers that distinguish between normal weight and obese adults, i.e., glutamine (higher in the normal group, p < 0.05), and lactate, BCAAs, acetoacetate and 3-hydroxybutyrate (higher in the obese group, p < 0.05). In addition, visceral fat and serum TG, glutamate, acetoacetate, N-acetyl glycoprotein, unsaturated lipid, isoleucine, and VLDL/LDL are higher (p < 0.05) in the obese with hyperlipidemia. Therefore, they can be used as biomarkers to identify these two types of obesity.

Protein binding of 4-hydroxybenzoic acid and 4-hydroxy-3-methoxybenzoic acid to human serum albumin and their anti-proliferation on doxorubicin-sensitive and doxorubicin-resistant leukemia cells.

4-Hydroxybenzoic acids (4-HBA) and 4-hydroxy-3-methoxybenzoic acid (Vanillic acid, VA) have exhibited several pharmacological activities. Generally, the biological activities of compounds are highly involved in the interaction between protein and compounds in blood plasma. The objective was to investigate the interaction of 4-HBA or VA with human serum albumin (HSA) and their anti-proliferation properties on doxorubicin-sensitive K562 and doxorubicin-resistant K562/Dox leukemia cells. The protein binding of 4-HBA or VA to HSA was investigated using fluorescence quenching at temperatures of 298 and 310 Kelvin (K) under the pH of 6.0, 7.4, and 8.0 conditions. The effect of 4-HBA and VA on anti-proliferation was also studied on doxorubicin-sensitive K562 and doxorubicin-resistant K562/Dox leukemia cells using resazurin assay. The results showed that 4-HBA and VA could interact with HSA. The fluorescence quenching process in HSA-4-HBA system might be attributed to static quenching mechanism. In contrast, a dynamic quenching mechanism might be mainly involved in the fluorescence quenching process in the HSA-VA system. Thermodynamic data suggested that the spontaneous interaction between HSA and 4-HBA or VA had occurred in the system and it also indicated that hydrogen bonds and Van der Waals forces contributed to the binding of HSA to 4-HBA or VA. In addition, 4-HBA and VA decreased K562 and K562/Dox cells viability in a dose- and time-dependence manner. In conclusions, the 4-HBA and VA could interact with HSA. In addition, the 4-HBA and VA decreased in cell viability for both doxorubicin-sensitive K562 and doxorubicin-resistant K562/Dox leukemia cells in a dose- and time-dependence manner. Therefore, these current studies could provide useful information about the nature of 4-HBA or VA binding to protein HSA and their anticancer activities in both of these types of leukemia cells. The cell death mechanisms should be investigated through future study.

Magnetic Resonance Spectroscopy of Hepatic Fat from Fundamental to Clinical Applications.

The number of individuals suffering from fatty liver is increasing worldwide, leading to interest in the noninvasive study of liver fat. Magnetic resonance spectroscopy (MRS) is a powerful tool that allows direct quantification of metabolites in tissue or areas of interest. MRS has been applied in both research and clinical studies to assess liver fat noninvasively in vivo. MRS has also demonstrated excellent performance in liver fat assessment with high sensitivity and specificity compared to biopsy and other imaging modalities. Because of these qualities, MRS has been generally accepted as the reference standard for the noninvasive measurement of liver steatosis. MRS is an evolving technique with high potential as a diagnostic tool in the clinical setting. This review aims to provide a brief overview of the MRS principle for liver fat assessment and its application, and to summarize the current state of MRS study in comparison to other techniques.

Challenges and optimization strategies in medical imaging service delivery during COVID-19.

In coronavirus disease 2019 (COVID-19), medical imaging plays an essential role in the diagnosis, management and disease progression surveillance. Chest radiography and computed tomography are commonly used imaging techniques globally during this pandemic. As the pandemic continues to unfold, many healthcare systems worldwide struggle to balance the heavy strain due to overwhelming demand for healthcare resources. Changes are required across the entire healthcare system and medical imaging departments are no exception. The COVID-19 pandemic had a devastating impact on medical imaging practices. It is now time to pay further attention to the profound challenges of COVID-19 on medical imaging services and develop effective strategies to get ahead of the crisis. Additionally, preparation for operations and survival in the post-pandemic future are necessary considerations. This review aims to comprehensively examine the challenges and optimization of delivering medical imaging services in relation to the current COVID-19 global pandemic, including the role of medical imaging during these challenging times and potential future directions post-COVID-19.

Different responses of normal cells (red blood cells) and cancer cells (K562 and K562/Dox cells) to low-dose 137Cs gamma-rays.

High-dose radiation is deleterious to cells or tissues. However, the health risks of exposure to low-dose radiation remain unclear. The present study aimed to investigate the biological responses of low-dose gamma-ray in vitro exposure to normal red blood cells (RBCs) and erythroleukemia (K562 and K562/Dox) cancer cells. Cells were given a low dose of 0.03, 0.05 and 0.1 mGy of 137Cs gamma-rays (at a dose rate of 0.001 Gy/min) under in vitro conditions. Cells exposed to 0 Gy served as controls. Hemolysis and reactive oxygen species (ROS) were measured in exposed RBCs following exposure to low-dose gamma-rays. In addition, complete blood count (CBC) parameters were determined in irradiated whole blood. For irradiated K562 and K562/Dox cancer cells, ROS and mitochondrial activity were measured at 0, 30, 60 and 120 post-irradiation times. The results showed no change in the percentage of ROS and hemolysis in irradiated RBCs. The data indicated no perturbation in the CBC parameters in irradiated whole blood. By contrast, statistically significant dose-dependent increases in the percentage of ROS and decreases in the mitochondrial activity in the K562 and K562/Dox cancer cells were observed from 0 min up to 120 min post-irradiation. These findings concluded that there were differences in biological responses in normal cells (RBCs) and cancer cells (K562 and K562/Dox) to low-dose gamma-rays when cells were irradiated under in vitro conditions.

Differences in Spectroscopic Properties of Saliva Taken From Normal Subjects and Oral Cancer Patients: Comparison Studies.

Oral cancer disease is among the most common cancers in the world and are associated with mortality and morbidity. The characterization of saliva samples may help to distinguish patients with oral cancer disease from normal subjects. To characterize spectra of saliva samples from normal subjects and oral cancer patients by use of fluorescence, absorption, and 1H-NMR spectroscopy. Whole unstimulated saliva samples were collected from patients with oral cancer disease and normal subjects. The saliva samples were analyzed by absorption, fluorescence and 1H-NMR spectroscopic techniques. The characteristic spectra of saliva samples from patients with oral cancer disease and normal subjects were compared. For fluorescence spectroscopic studies, six fluorophores were found in saliva samples. Autofluorescence emission spectra and synchronous spectra of saliva were different between normal subjects and oral cancer patients. For absorption spectroscopic studies, the typical absorption spectra of saliva samples from normal subjects and oral cancer patients were also different in absorption intensity, 1st and 2nd derivative of absorption spectra values. For 1H-NMR studies, nine metabolites and four metabolites were found in saliva samples taken from normal subjects and oral cancer patients, respectively. The metabolic profiles of saliva samples from normal subjects and oral cancer patients were not similar. The characteristic spectra of saliva samples from normal subjects and oral cancer patients were found. These results showed differences in the spectra of saliva samples between both that groups. The spectra from each spectroscopic techniques could determine a candidate saliva biomarkers for distinguishing patients with oral cancer disease from normal subjects.

Dapagliflozin ameliorates pancreatic injury and activates kidney autophagy by modulating the AMPK/mTOR signaling pathway in obese rats.

Chronic consumption of a high-fat diet induces obesity and impairs the ultra-structure of organs and tissues. We examined the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor-dapagliflozin on renal and pancreatic injuries in obese condition. Rats were fed a high-fat diet for 16 weeks to induce obesity. After that, dapagliflozin or vildagliptin, 1.0 or 3.0 mg/kg/day, respectively, was administered by oral gavage for 4 weeks. The effects of dapagliflozin on insulin resistance, kidney autophagy, pancreatic oxidative stress, endoplasmic reticulum (ER) stress, inflammation, and apoptosis in high-fat diet-induced obese rats were elucidated. High-fat-diet fed rats demonstrated metabolic abnormalities including increased body weight, visceral fat weight, plasma insulin, plasma cholesterol, homeostasis model assessment (HOMA) index, and TAUCg, indicating the obese-insulin resistant and glucose intolerance conditions. Also, high-fat-diet fed rats exhibited significant pancreatic injury accompanied by decreased kidney autophagy. Dapagliflozin or vildagliptin treatment for 4 weeks ameliorated pancreatic oxidative stress, ER stress, inflammation, and apoptosis and restored kidney autophagy in obese rats. Moreover, the morphology changes of the pancreas and kidney were improved in the treated groups. Interestingly, dapagliflozin showed higher efficacy than vildagliptin in improving body weight, visceral fat weight, plasma cholesterol level, and pancreatic oxidative stress in our model. Taken together, the present study demonstrated that the therapeutic effects of dapagliflozin attenuated pancreatic injury, pancreatic oxidative stress, ER stress, inflammation, apoptosis, and exerted renoprotective effects by restoring autophagic signaling in obese rats.

Autophagy participants in the dedifferentiation of mouse 3T3-L1 adipocytes triggered by hypofunction of insulin signaling.

Our previous data indicate that both insulin and IGF-1 signallings dysfunction promotes the dedifferentiation of primary human and mouse white adipocytes. Based on the fact that insulin activates mTOR and inhibits autophagy, and autophagy deficiency can inhibit the differentiation of white adipocytes, we speculate that autophagy may be related to the dedifferentiation of white adipocytes. We investigated the underlying mechanism of autophagy during dedifferentiation of mouse 3T3-L1 adipocytes. After incomplete inhibition of insulin and IGF-1 signallings, 3T3-L1 adipocytes manifest dedifferentiation accompanied with an increase of autophagy level. If induction only of autophagy in the adipocytes, then the cells also occur somewhat dedifferentiation, and with a slight decrease of insulin signal, while its degree was weaker than insulin signal inhibited cells. Notably, after inhibition of the insulin and IGF-1 signallings and simultaneously inducing autophagy, the dedifferentiation of 3T3-L1 adipocytes was the most obvious compared with other groups, and the insulin and IGF-1 signallings decreases was greater than the cells with inhibition only of insulin signalling. If inhibition of both insulin signal and autophagy simultaneously, the dedifferentiation of the adipocytes reveals similar tendencies to the cells that insulin signal was inhibited. No significant dedifferentiation occurs of 3T3-L1 cells if only inhibition of autophagy. Taken all together, in this study, we proved that autophagy is positively related to the dedifferentiation of 3T3-L1 adipocytes and is regulated through the insulin-PI3K-AKT-mTOCR1-autophagy pathway. Autophagy may also has a certain degree of negative feedback affect on the insulin signalling of 3T3-L1 cells. Our work may help to better understand the biological properties of mature adipocytes and may help formulate anti-obesity strategies by regulating insulin and insulin signaling level.

Fornix Integrity Is Differently Associated With Cognition in Healthy Aging and Non-amnestic Mild Cognitive Impairment: A Pilot Diffusion Tensor Imaging Study in Thai Older Adults.

Damage to the fornix leads to significant memory impairment and executive dysfunction and is associated with dementia risk. We sought to identify if fornix integrity and fiber length are disrupted in mild cognitive impairment (MCI) and how they associate with cognition. Data from 14 healthy older adult controls (HCs) and 17 subjects with non-amnestic MCI (n-aMCI) were analyzed. Diffusion tensor imaging (DTI) at 1.5 Tesla MRI was performed to enable manual tracing of the fornix and calculation of DTI parameters. Higher fractional anisotropy of body and column of the fornix was associated with better executive functioning and memory, more strongly in the HC than in the n-aMCI group. Fornix fiber tract length (FTL) was associated with better executive function, more strongly in the n-aMCI than in the HC group, and with better memory, more strongly in the HC than in the n-aMCI group. These results highlight a decline in the contributions of the fornix to cognition in n-aMCI and suggest that maintenance of fornix FTL is essential for sustaining executive functioning in people with n-aMCI.