68 research outputs found
Modeling the effect of levothyroxine therapy on bone mass density in postmenopausal women: a different approach leads to new inference
<p>Abstract</p> <p>Background</p> <p>The diagnosis, treatment and prevention of osteoporosis is a national health emergency. Osteoporosis quietly progresses without symptoms until late stage complications occur. Older patients are more commonly at risk of fractures due to osteoporosis. The fracture risk increases when suppressive doses of levothyroxine are administered especially in postmenopausal women. The question is; "When should bone mass density be tested in postmenopausal women after the initiation of suppressive levothyroxine therapy?". Standard guidelines for the prevention of osteoporosis suggest that follow-up be done in 1 to 2 years. We were interested in predicting the level of bone mass density in postmenopausal women after the initiation of suppressive levothyroxine therapy with a novel approach.</p> <p>Methods</p> <p>The study used data from the literature on the influence of exogenous thyroid hormones on bone mass density. Four cubic polynomial equations were obtained by curve fitting for Ward's triangle, trochanter, spine and femoral neck. The behaviors of the models were investigated by statistical and mathematical analyses.</p> <p>Results</p> <p>There are four points of inflexion on the graphs of the first derivatives of the equations with respect to time at about 6, 5, 7 and 5 months. In other words, there is a maximum speed of bone loss around the 6<sup>th </sup>month after the start of suppressive L-thyroxine therapy in post-menopausal women.</p> <p>Conclusion</p> <p>It seems reasonable to check bone mass density at the 6<sup>th </sup>month of therapy. More research is needed to explain the cause and to confirm the clinical application of this phenomenon for osteoporosis, but such an approach can be used as a guide to future experimentation. The investigation of change over time may lead to more sophisticated decision making in a wide variety of clinical problems.</p
Single-cell transcriptome analysis for cancer and biology of the pancreas: A review on recent progress
Single-cell sequencing has become one of the most used techniques across the wide field of biology. It has enabled researchers to investigate the whole transcriptome at the cellular level across tissues, which unlocks numerous potentials for basic and applied studies in future diagnosis and therapy. Here, we review the impact of single-cell RNA sequencing, as the prominent single-cell technique, in pancreatic biology and cancer. We discuss the most recent findings about pancreatic physiology and pathophysiology owing to this technological advancement in the past few years. Using single-cell RNA sequencing, researchers have been able to discover cellular heterogeneity across healthy cell types, as well as cancer tissues of the pancreas. We will discuss the new immunological targets and new molecular mechanisms of progression in the microenvironment of pancreatic cancer studied using single-cell RNA sequencing. The scope is not limited to cancer tissues, and we cover novel developmental, evolutionary, physiological, and heterogenic insights that have also been achieved recently for pancreatic tissues. We cover all biological insights derived from the single-cell RNA sequencing data, discuss the corresponding pros and cons, and finally, conclude how future research can move better by utilizing single-cell analysis for pancreatic biology
Anti-inflammatory effect of AMPK signaling pathway in rat model of diabetic neuropathy
Abstract Diabetic neuropathy (DN) is characterized as
Hyperglycemia activates thdisturbed nerve conduction and
progressive chronic pain. Inflammatory mediators, particularly
cytokines, have a determinant role in the
pathogenesis of neuropathic pain. The activity of adenosine
monophosphate protein kinase (AMPK), an energy charge
sensor with neuroprotective properties, is decreased in
diabetes. It has been reported that activation of AMPK
reduces the systemic inflammation through inhibition of
cytokines. In this study, we aimed to investigate the
probable protective effects of AMPK on DN in a rat of
diabetes. DN was induced by injection of streptozotocin
(65 mg/kg, i.p.). Motor nerve conduction velocities
(MNCV) of the sciatic nerve, as an electrophysiological
marker for peripheral nerve damage, were measured.
Plasma levels of IL-6, TNF-a, CRP were assessed as
relevant markers for inflammatory response. Also, the
expression of phosphorylated AMPK (p-AMPK) and nonphosphorylated
(non-p-AMPK) was evaluated by western
blotting in the dorsal root ganglia. Histopathological
assessment was performed to determine the extent of nerve
damage in sciatic nerve. Our findings showed that activation
of AMPK by metformin (300 mg/kg) significantly
increased the MNCV and reduced the levels of inflammatory
cytokines. In addition, we showed that administration
of metformin increased the expression of p-AMPK as well
as decline in the level of non p-AMPK. Our results
demonstrated that co-administration of dorsomorphin with
metformin reversed the beneficial effects of metformin. In
conclusion, the results of this study demonstrated that the
activation of AMPK signaling pathway in diabetic neuropathy
might be associated with the anti-inflammatory
response
Shift working and risk of lipid disorders: A cross-sectional study
BACKGROUND: previous studies have indicated on association between shift work and lipid profile disturbances. Lipid profile disturbances could be due to internal desynchronization. The aim of this study was to analyze whether there is relationship between shift work and serum lipids, fasting blood glucose and hypertension. RESULTS: A total of 424 rail road workers between the ages of 21 and 64 years in this study filled out a questionnaire, and total cholesterol, triglyceride and HDL-C concentration were measured after 12-hours fasting. Association between shift work and biochemical variables and blood pressure were measured. The X(2 )and fisher's exact test was used for comparing the qualitative variables and for quantitative variables with normal distribution we used the parametric tests. Odds ratio (OR) with the 95% confidence interval (95% CI) was used for comparing the proportions of risk variables. Sub-populations in this study were consisting of 158 (37.3%) shift workers and 266 (62.7%) day workers. High levels of total cholesterol (> 200 mg/dl) and LDL-cholesterol (> 130 mg/dl) were significantly more prevalent in nearly all groups of shift workers irrespective of age. But there is no differences in the serum levels of triglyceride, HDL-C, fasting blood glucose and blood pressure between shift workers and day workers. Adjusted Odd's ratio for the effect of shift working on high serum total cholesterol and LDL-C level were 2.11(95%CI: 1.33–3.36) and 1.76(95%CI: 1.09–2.83), respectively. CONCLUSION: This study showed that high serum total cholesterol and LDL-C level were more common in shift workers than in day workers. This finding persisted after adjustment was made for age and food type. But there was no difference in the prevalence of HDL-C, triglyceride, fasting blood glucose and hypertension between shift working and day working. It was concluded that shift work is a risk factor for lipid profile disturbances
Tropisetron suppresses colitis-associated cancer in a mouse model in the remission stage
Patients with inflammatory bowel disease (IBD) have a high risk for development of colitis-associated cancer
(CAC). Serotonin is a neurotransmitter produced by enterochromaffin cells of the intestine. Serotonin and its receptors,
mainly 5-HT3 receptor, are overexpressed in IBD and promote development of CAC through production
of inflammatory cytokines. In the present study, we demonstrated the in vivo activity of tropisetron, a 5-HT3 receptor
antagonist, against experimental CAC. CAC was induced by azoxymethane (AOM)/dextran sodium sulfate
(DDS) in BALB/c mice. The histopathology of colon tissue was performed. Beta-catenin and Cox-2 expression was
evaluated by immunohistochemistry as well as quantitative reverse transcription-PCR (qRT-PCR). Alterations in
the expression of 5-HT3 receptor and inflammatory-associated genes such as Il-1β, Tnf-α, Tlr4 and Myd88 were
determined by qRT-PCR. Our results showed that tumor development in tropisetron-treated CAC group was significantly
lower than the controls. The qRT-PCR analysis demonstrated that the expression of 5-HT3 receptor was
significantly increased following CAC induction. In addition, tropisetron reduced expression of β-catenin and
Cox-2 in the CAC experimental group. The levels of Il-1β, Tnf-α, Tlr4 and Myd88 were significantly decreased
upon tropisetron treatment in the AOM/DSS group. Taken together, our data show that tropisetron inhibits development
of CAC probably by attenuation of inflammatory reactions in the colitis
Effects of Levothyroxine and Liothyronine on Cirrhotic Cardiomyopathy in Rats
In liver cirrhosis, there is low T3 syndrome associated with a decrease in total triiodothyronine (T3) and free T3 concentrations and cirrhotic cardiomyopathy (CCM) with chronotropic incompetence. Thus, we aimed to investigate the effects of eliminating T3 and thyroxine (T4) deficiencies on cardiac chronotropic dysfunction. Bile duct ligation (BDL) was used to induce cirrhosis in male Wistar rats. The chronotropic responses were studied through the Power Lab system in sham/saline, sham/T3T4, BDL/saline, and BDL/T3T4 groups. The serum T3 and T4, and T3 resin uptake (T3RU) levels were assessed. The atrial T3 receptor expression was investigated through a real-time polymerase chain reaction (Real-time PCR). The chronotropic responses were decreased in the BDL/saline group and raised in the BDL/T3T4 group. The serum T3 levels decreased in the BDL/saline group compared to sham group, but increased in the BDL/T3T4 group compared to the BDL/saline group. The serum T4 level increased in the BDL/saline and decreased in the BDL/T3T4 group. The serum T3RU level decreased in the BDL/saline and increased in the BDL/T3T4 group. The T3 receptor expression in atria increased in the BDL/saline group, nonetheless, it did not change in the BDL/T3T4 group compared to the sham/saline and the BDL/saline groups. T3T4 treatment did not increase the chronotropic response in the control group but the treatment improved the chronotropic hyporesponsiveness, and serum T4 and T3 RU abnormalities in cirrhosis, however, it is not related to the atrial T3 receptor expression
Acute Transplantation of Human Olfactory Mucosa-Derived Olfactory Ensheathing Cells Fails to Improve Locomotor Recovery in Rats
Olfactory ensheathing cells-based therapy for spinal cord injury (SCI) repair has been a possible treatment for clinical study because of their safety in autologous transplantation and potential regenerative capability. However, there are contradictory reports on the results after transplantation in animal models. The purpose of this research was to investigate the effect of acute transplantation of human mucosa-derived olfactory ensheathing cells (OECs) on the repair of the spinal cord. Human olfactory ensheathing cells were isolated from the human mucosa and cultured under supplemented neuronal cell culture medium. They were characterized by immunocytochemistry for olfactory ensheathing cell markers. We induced spinal cord injury at T8-T9 of rats by aneurysm clips and simultaneously injected two million OECs into subarachnoid space of spinal cord. Sensory and motor behaviors were recorded by tail-flick reflex (TFR) and BBB scores, respectively every week for seven weeks after injury. Morphology and S100-beta antigen expression in olfactory ensheathing cells of the human olfactory mucosa was confirmed by immunostaining. OECs transplantation did not recover inflammation, neuronal vacuolation, hemorrhage, and cyst formation. These findings suggest that OECs transplantation in this experimental setting did not lead to tissue regeneration to enhance locomotion. These results broaden current knowledge and are additions to the science and literature
National, sub-national, and risk-attributed burden of thyroid cancer in Iran from 1990 to 2019
An updated exploration of the burden of thyroid cancer across a country is always required for making correct decisions. The objective of this study is to present the thyroid cancer burden and attributed burden to the high Body Mass Index (BMI) in Iran at national and sub-national levels from 1990 to 2019. The data was obtained from the GBD 2019 study estimates. To explain the pattern of changes in incidence from 1990 to 2019, decomposition analysis was conducted. Besides, the attribution of high BMI in the thyroid cancer DALYs and deaths were obtained. The age-standardized incidence rate of thyroid cancer was 1.57 (95% UI: 1.33–1.86) in 1990 and increased 131% (53–191) until 2019. The age-standardized prevalence rate of thyroid cancer was 30.19 (18.75–34.55) in 2019 which increased 164% (77–246) from 11.44 (9.38–13.85) in 1990. In 2019, the death rate, and Disability-adjusted life years of thyroid cancer was 0.49 (0.36–0.53), and 13.16 (8.93–14.62), respectively. These numbers also increased since 1990. The DALYs and deaths attributable to high BMI was 1.91 (0.95–3.11) and 0.07 (0.04–0.11), respectively. The thyroid cancer burden and high BMI attributed burden has increased from 1990 to 2019 in Iran. This study and similar studies’ results can be used for accurate resource allocation for efficient management and all potential risks’ modification for thyroid cancer with a cost-conscious view
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