Thermal mapping: Assessing the optimal sites for temperature measurement in the human body and emerging technologies.

Numerous body locations have been utilized to obtain an accurate body temperature. While some are commonly used, their accuracy, response time, invasiveness varies greatly, and determines their potential clinical and/or research use. This review discusses human body temperature locations, their accuracy, ease of use, advantages, and drawbacks. We explain the concept of core body temperature and which of the locations achieve the best correlation to this temperature. The body locations include axilla, oral cavity, rectum, digestive and urinary tracts, skin, tympanic, nasopharynx, esophagus, and pulmonary artery. The review also discusses the latest temperature technologies, heat-flux technology and telemetric ingestible temperature pills, and the body locations used to validate these devices. Rectal and esophageal measurements are the most frequently used.

Nephrotic syndrome in the elderly: epidemiological aspects, clinical data, and renal biopsy findings.

Nephrotic syndrome is the most common clinical presentation of glomerular disease in elderly patients, and renal biopsy is an important diagnostic resource. The aim of this study was to describe nephrotic syndrome among elderly patients in Brazil, focusing on tubulointerstitial and vascular involvement. This was a retrospective study of patients over 65 years of age with nephrotic syndrome who underwent renal biopsy between January 2012 and December 2019. Of the 123 renal biopsies that occurred during the study period, 44 (35.8%) were performed for the investigation of nephrotic syndrome. Among those 44 cases, the main etiologies were membranous nephropathy in 13 cases (29.5%), amyloidosis in ten (22.7%), non-collapsing focal segmental glomerulosclerosis (FSGS) in four (9.1%), and collapsing FSGS in four (9.1%). Patients with minimal change disease (MCD) had the lowest degree of interstitial fibrosis compared with the other glomerulopathies, and histological signs of acute tubular necrosis (ATN) were less common among those with amyloidosis than among those with membranous nephropathy, FSGS, or MCD (P=0.0077). Of the patients with ATN, the frequency of acute kidney injury (AKI) was highest in those with MCD (P<0.001). All patients had some degree of vascular involvement, regardless of the type of glomerulopathy. In conclusion, the second most common cause of nephrotic syndrome in this population was amyloidosis, and acute interstitial tubule involvement was more marked in MCD. Vascular involvement is something that cannot be dissociated from the age of the patient and is not only due to the underlying glomerulopathy.

Nephrotic syndrome in the elderly: epidemiological aspects, clinical data, and renal biopsy findings

Nephrotic syndrome is the most common clinical presentation of glomerular disease in elderly patients, and renal biopsy is an important diagnostic resource. The aim of this study was to describe nephrotic syndrome among elderly patients in Brazil, focusing on tubulointerstitial and vascular involvement. This was a retrospective study of patients over 65 years of age with nephrotic syndrome who underwent renal biopsy between January 2012 and December 2019. Of the 123 renal biopsies that occurred during the study period, 44 (35.8%) were performed for the investigation of nephrotic syndrome. Among those 44 cases, the main etiologies were membranous nephropathy in 13 cases (29.5%), amyloidosis in ten (22.7%), non-collapsing focal segmental glomerulosclerosis (FSGS) in four (9.1%), and collapsing FSGS in four (9.1%). Patients with minimal change disease (MCD) had the lowest degree of interstitial fibrosis compared with the other glomerulopathies, and histological signs of acute tubular necrosis (ATN) were less common among those with amyloidosis than among those with membranous nephropathy, FSGS, or MCD (P=0.0077). Of the patients with ATN, the frequency of acute kidney injury (AKI) was highest in those with MCD (P<0.001). All patients had some degree of vascular involvement, regardless of the type of glomerulopathy. In conclusion, the second most common cause of nephrotic syndrome in this population was amyloidosis, and acute interstitial tubule involvement was more marked in MCD. Vascular involvement is something that cannot be dissociated from the age of the patient and is not only due to the underlying glomerulopathy.

Cytotoxic effect of carbohydrate derivatives of digitoxigenin involves modulation of plasma membrane Ca2+ -ATPase.

Cardiac glycosides, such as digoxin and digitoxin, are compounds that interact with Na+ /K+ -ATPase to induce anti-neoplastic effects; however, these cardiac glycosides have narrow therapeutic index. Thus, semi-synthetic analogs of digitoxin with modifications in the sugar moiety has been shown to be an interesting approach to obtain more selective and more effective analogs than the parent natural product. Therefore, the aim of this study was to assess the cytotoxic potential of novel digitoxigenin derivatives, digitoxigenin-α-L-rhamno-pyranoside (1) and digitoxigenin-α-L-amiceto-pyranoside (2), in cervical carcinoma cells (HeLa) and human diploid lung fibroblasts (Wi-26-VA4). In addition, we studied the anticancer mechanisms of action of these compounds by comparing its cytotoxic effects with the potential to modulate the activity of three P-type ATPases; Na+ /K+ -ATPase, sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA), and plasma membrane Ca2+ -ATPase (PMCA). Briefly, the results showed that compounds 1 and 2 were more cytotoxic and selectivity for HeLa tumor cells than the nontumor cells Wi-26-VA4. While the anticancer cytotoxicity in HeLa cells involves the modulation of Na+ /K+ -ATPase, PMCA and SERCA, the modulation of these P-type ATPases was completely absent in Wi-26-VA4 cells, which suggest the importance of their role in the cytotoxic effect of compounds 1 and 2 in HeLa cells. Furthermore, the compound 2 inhibited directly erythrocyte ghosts PMCA and both compounds were more cytotoxic than digitoxin in HeLa cells. These results provide a better understanding of the mode of action of the synthetic cardiac glycosides and highlights 1 and 2 as potential anticancer agents.

Exchange-bias and magnetic anisotropy fields in core-shell ferrite nanoparticles.

Exchange bias properties of MnFe[Formula: see text]O[Formula: see text]@[Formula: see text]-Fe[Formula: see text]O[Formula: see text] core-shell nanoparticles are investigated. The measured field and temperature dependencies of the magnetization point out a well-ordered ferrimagnetic core surrounded by a layer with spin glass-like arrangement. Quasi-static SQUID magnetization measurements are presented along with high-amplitude pulse ones and are cross-analyzed by comparison against ferromagnetic resonance experiments at 9 GHz. These measurements allow one to discern three types of magnetic anisotropies affecting the dynamics of the magnetic moment of the well-ordered ferrimagnetic NP's core viz. the easy-axis (uniaxial) anisotropy, the unidirectional exchange-bias anisotropy and the rotatable anisotropy. The uniaxial anisotropy originates from the structural core-shell interface. The unidirectional exchange-bias anisotropy is associated with the spin-coupling at the ferrimagnetic/spin glass-like interface; it is observable only at low temperatures after a field-cooling process. The rotatable anisotropy is caused by partially-pinned spins at the core/shell interface; it manifests itself as an intrinsic field always parallel to the external applied magnetic field. The whole set of experimental results is interpreted in the framework of superparamagnetic theory, i.e., essentially taking into account the effect of thermal fluctuations on the magnetic moment of the particle core. In particular, it is found that the rotatable anisotropy of our system is of a uniaxial type.

Expression of bone morphogenetic protein 10 in cases with endometrial carcinoma and its clinical significance.

PURPOSE: To investigate the expression of bone morphogenetic protein 10 (BMP-10) in patients with endometrial carcinoma (EC) and its clinical significance. METHODS: Totally 143 cancer tissue specimens were sampled from patients with EC and retrospectively analyzed. The immunohistochemical method was adopted for quantifying BMP-10 in EC tissues. Then the patients were assigned to high and low BMP-10 expression groups. The Kaplan-Meier method and log-rank test were adopted to compare the difference of tumor-free survival (TFS) rate and overall survival (OS) rate between the two groups. The COX proportional hazard model was used to analyze independent risk factors affecting the TFS rate and OS rate of patients with EC. RESULTS: There were 80 patients (55.94%) with low BMP-10 expression and 63 patients with high BMP-10 expression (54.06%). BMP-10 expression was significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.001), myometrial invasion depth (P < 0.001), histological grade (P < 0.001), and lymph node metastasis (P = 0.009). Additionally, TFS rate (P = 0.004) and OS rate (P = 0.003) in the low BMP-10 expression group were notably lower than those in the high BMP-10 expression group. Multivariate analysis showed that BMP-10 expression (HR: 13.712, 95% CI 1.823-103.158, P = 0.011) was an independent risk factor for the TFS of patients with EC. FIGO stage (P = 0.001) and BMP-10 expression (HR: 8.655, 95% CI 1.098-68.215, P = 0.020) were independent risk factors for the OS of such patients. CONCLUSIONS: BMP-10 can be adopted as a molecular marker for predicting the poor prognosis of patients with EC.

Method of determining the location of the sexual neurovascular bundle (internal pudendal artery, internal pudendal vein and pudendal nerve) / Método para determinar la ubicación del haz neurovascular sexual (vena y arteria pudenda interna y nervio pudendo)

Disorders in the course of the neurovascular bed of the sexual neurovascular bundle (NVB) entail problems of gynecological, andrological and urological nature, for example, the state of impotence in men. The aim of the study was to establish a method to determine a projection. The Arteria pudenda interna, Vena pudenda interna and Nervus pudendus (sexual neurovascular bundle or NVB) from the infrapiriform foramen to the Alcock's canal (pudendal canal) in which the pudendal neurovascular bundle runs. Topographic and anatomical study was performed on 15 corpses without organ complex (remote shore): 9-from men and 6-women, aged 36 to 74 years. Each object of study (corpse) included 2 pairs of sexual NVB, a total of 30 investigated. The information obtained on the projection branches of the pudendal nerve, and pudendal internal artery and pudendal internal vein from infrapiriform foramen to the entrance of the pudendal canal. A method for determining the projection of sexual NVB in the gluteal region was developed. The projection of Arteria pudenda interna, Vena pudenda interna and Nervus pudendus from the infrapiriform foramen in the gluteal region and to the entrance of the pudendal canal is determined. The morphometric data necessary for the mathematical equation developed by us for the calculation of the boundaries of the projection of the desired plane in the course of the sexual NVB are obtained . Using these data in the method of mathematical calculation developed by us using the formula C'c' = 0,2679 x (A'G-AD+3), we determined the projection of the figure, in the form of a trapezoid, in the center of which the projection of the sexual NVB is determined.A method for determining the projection of the sexual neurovascular bundle in the gluteal region for diagnosis and therapeutic effects on sexual NPS was developed.

Los trastornos en el curso de las estructuras del haz neurovascular sexual conllevan problemas de naturaleza ginecológica, andrológica y urológica, por ejemplo, el estado de impotencia en los hombres. El objetivo de este estudio fue establecer un método para determinar una proyección de los vasos pudendos internos y el nervio pudendo (haz neurovascular sexual o HNV) desde el foramen infrapiriforme hasta el canal de Alcock (canal pudendo). Se realizó un estudio topográfico y anatómico en 15 cadáveres: 9 hombres y 6 mujeres, entre 36 y 74 años. Se analizaron 30 muestras, cada cadáver incluyó 2 pares de HNV sexuales. Se obtuvo información sobre las ramas de proyección de la arteria, y vena pudenda interna y del nervio pudendo, desde el foramen infrapiriforme hasta la entrada al canal pudendo. Se desarrolló un método para determinar la proyección de NVB sexual en la región glútea. La proyección de la vena pudenda interna y del nervio pudendo se determinó desde el foramen infrapiriformis en la región glútea, hasta la entrada del canal pudendo. Se obtuvieron datos morfométricos necesarios para la ecuación matemática y obtener el cálculo de los límites de la proyección del plano deseado en el curso de la HNV sexual. Usando estos datos se utilizó la fórmula C'c '= 0,2679 x (A'G-AD + 3), y se realizó la proyección de la figura, en forma de trapecio, en el centro del cual se determinó la proyección de la HNV sexual. Se desarrolló un método para la proyección del haz neurovascular sexual en la región glútea, en el diagnóstico y los efectos terapéuticos sobre el NPS sexual.

Older age of childhood type 1 diabetes onset is associated with islet autoantibody positivity >30 years later: the Pittsburgh Epidemiology of Diabetes Complications Study.

AIMS: To examine the association between islet autoantibody positivity and clinical characteristics, residual ß-cell function (C-peptide) and prevalence of complications in a childhood-onset (age <17 years), long-duration (≥32 years) type 1 diabetes cohort. METHODS: Islet autoantibodies (glutamic acid decarboxylase, insulinoma-associated protein 2 and zinc transporter-8 antibodies) were measured in the serum of participants who attended the 2011-2013 Pittsburgh Epidemiology of Diabetes Complications study follow-up examination (n=177, mean age 51 years, diabetes duration 43 years). RESULTS: Prevalences of islet autoantibodies were: glutamic acid decarboxylase, 32%; insulinoma-associated protein 2, 22%; and zinc transporter-8, 4%. Positivity for each islet autoantibody was associated with older age at diabetes onset (glutamic acid decarboxylase antibodies, P=0.03; insulinoma-associated protein 2 antibodies, P=0.001; zinc transporter-8 antibodies, P<0.0001). Older age at onset was also associated with an increasing number of autoantibodies (P = 0.001). Glutamic acid decarboxylase antibody positivity was also associated with lower HbA1c (P = 0.02), insulinoma-associated protein 2 antibody positivity was associated with lower prevalence of severe hypoglycaemic episodes (P=0.02) and both distal and autonomic neuropathy (P=0.04 for both), and zinc transporter-8 antibody positivity was associated with higher total and LDL cholesterol (P=0.01). No association between autoantibody positivity and C-peptide was observed. CONCLUSIONS: The strong association between islet autoantibody positivity and older age at type 1 diabetes onset supports the hypothesis of a less aggressive, and thus more persistent, immune process in those with older age at onset. This observation suggests that there may be long-term persistence of heterogeneity in the underlying autoimmune process.

Prognostic implication of EGFR mutation status and subtype in resected lung adenocarcinoma patients irrespective of therapy.

OBJECTIVE: This study aimed to investigate the pure prognostic role of epidermal growth factor receptor (EGFR) mutation status and subtype in lung adenocarcinoma patients irrespective of therapy. MATERIALS AND METHODS: We retrospectively enrolled 119 cases of completely resected pathological stage I lung adenocarcinoma patients who received no postoperative chemotherapy or tyrosine kinase inhibitors. EGFR gene mutations from 18 to 21 exons were tested for all the patients. Disease-free survival (DFS) and overall survival (OS) were compared between patients with different EGFR mutation status and subtype using Kaplan-Meier methods. RESULTS: EGFR mutations were detected in 54 (45.4%) patients including two common mutation subtypes: 32 in-frame deletion within exon 19 (19del) and 19 point mutation within exon 21 (L858R). The frequency of EGFR mutations was much greater for patients of non-smokers versus current or ever smokers (58.1 versus 24.4%, P = 0.000), and a little greater for females versus males (53.8 versus 35.2%, P = 0.042). The median follow-up duration was 43.5 months, and there were no differences on DFS (P = 0.461) and OS (P = 0.989) between patients with EGFR mutations and those without in univariate analysis. The patients harboring 19del mutation had a better DFS (P = 0.028) and OS (P = 0.001) than the patients harboring L858R mutation with significant statistical difference. CONCLUSIONS: This study suggests that there is no difference on survival between patients with EGFR mutations and those without, but the patients harboring EGFR 19del mutation have survival advantage compared to those harboring EGFR L858R mutation.

High calpain-1 expression predicts a poor clinical outcome and contributes to tumor progression in pancreatic cancer patients.

BACKGROUND: Pancreatic cancer (PC) is a highly aggressive and metastatic disease, with an elevated mortality rate. It is, therefore, crucial to assess factors affecting the prognosis of PC patients. Meanwhile, calpain-1 is associated with malignant tumor progression and metastasis. Thus, it is meaningful to evaluate the relationship between calpain-1 and PC. MATERIALS AND METHODS: Calpain-1 protein expression was assessed by immunohistochemistry in 96 pancreatic cancer samples and paired adjacent non-cancerous specimens. In addition, calpain-1 protein levels were assessed in six PC cell lines by western blot (WB). Next, PC cells were transfected with calpain-1 siRNA, and silencing was confirmed by WB. Finally, cell proliferation, colony formation, migration and invasion assays, and cell apoptosis analysis were performed to examine the effects of calpain-1 knockdown on proliferation, growth, apoptosis, migration, and invasion in PC cells. RESULTS: The results showed that calpain-1 was overexpressed in PC tissues and cells. Meanwhile, calpain-1 overexpression was associated with tumor site (P = 0.029), metastasis (P = 0.000), and TNM stage (P = 0.000), but showed no associations with histological grade (P = 0.396), age (P = 0.809), sex (P = 1.000), and lesion size (P = 0.679). The Kaplan-Meier method demonstrated that the low calpain-1 expression group had increased overall survival (OS) compared with patients expressing high calpain-1 levels (28.7 ± 4.1 vs. 17.0 ± 2.3 months) (P = 0.005). Besides, calpain-1 in PC cells was successfully silenced by liposome-mediated RNA interference, resulting in reduced cell growth, invasion, and metastasis in PC cells, with no effect on apoptosis. CONCLUSION: The above findings suggest that calpain-1 should be considered a potential biomarker for PC prognosis and therapy.

Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge.

Among the novel class of endogenous long non-coding RNAs, circular RNA (circRNA) is known as a key regulator in the development and progression of different cancers. Its function and mechanism in the tumorigenesis of colorectal cancer, however, has not been well studied. This study thus aimed to investigate potential regulation of colorectal cancer by circRNAs and the corresponding regulatory mechanism. We demonstrated that the expression of circRNA hsa_circ_0000523 (also known as circ_006229) was down-regulated in different colorectal cancer cell lines. It was also found that interference of hsa_circ_0000523 induced proliferation and suppressed apoptosis of colorectal cancer cells, the proliferation rate of which was reduced by the overexpression of hsa_circ_0000523. In addition, we found that miR-31 could recognize hsa_circ_0000523 sequence and that it acted as a "sponge" of miR-31, indirectly regulating Wnt/ß-catenin signaling pathway, which was involved in the progression of colorectal cancer. The results suggested that the expression of hsa_circ_0000523 correlated to the tumorigenesis of colorectal cancer cells. In addition, as a sponge of miR-31, the low level of hsa_circ_0000523 led to activation of Wnt/ß-catenin signaling pathway, inducing the subsequent progress of colorectal cancer.

Prevalencia de cardiopatía isquémica asintomática en pacientes con diabetes mellitus tipo 2 / Prevalence of asymptomatic ischaemic heart disease in patients with type 2 diabetes mellitus

Resumen Introducción: La enfermedad cardiovascular es la causa principal de muerte en pacientes con diabetes mellitus. La prevalencia de cardiopatía isquémica asintomática es más alta en pacientes diabéticos que en no diabéticos y se asocia a peor pronóstico. Objetivo: Identificar la prevalencia de cardiopatía isquémica asintomática en pacientes con diabetes mellitus tipo 2 en un hospital de tercer nivel de atención de Guatemala y analizar la posible asociación de dicha enfermedad con características epidemiológicas, clínicas y metabólicas. Métodos: Estudio de corte transversal en el que se estudió una muestra de 92 pacientes diabéticos seleccionados de forma aleatoria simple. Se realizó electrocardiograma, que cuando fue negativo para isquemia ameritó prueba de esfuerzo, o de lo contrario, ecocardiograma de estrés con dobutamina. Resultados: La edad media de los participantes fue de 57 años, 88% de los cuales eran mujeres; la duración media de la diabetes fue 7 años. Se encontró cardiopatía isquémica asintomática en el 22,8% de los casos. No se hallaron posibles asociaciones entre cardiopatía isquémica asintomática y edad, sexo, enfermedad arterial periférica, índice de masa corporal, índice tobillo-brazo, hipertensión arterial, dislipidemia, tabaquismo activo, sedentarismo, sobrepeso/obesidad, alcoholismo, glucosa en ayunas, hemoglobina glicosilada, colesterol total, colesterol HDL, colesterol LDL, ácido úrico, creatinina, tasa de filtrado glomerular y microalbuminuria. Conclusiones: La prevalencia de cardiopatía isquémica asintomática en la población estudiada con diabetes mellitus tipo 2 fue de 22,8%. No se encontraron posibles asociaciones de cardiopatía isquémica asintomática con las variables estudiadas.

Abstract Introduction: Cardiovascular disease is the main cause of death in patients with diabetes mellitus. The prevalence of asymptomatic ischaemic heart disease is higher in diabetic patients than in non-diabetic ones, and is associated with a worse prognosis. Objective: To determine the prevalence of asymptomatic ischaemic heart disease in patients with type 2 diabetes mellitus in a third level of care hospital in Guatemala, as well as to analyse the possible relationship of this disease with epidemiological, clinical, and metabolic characteristics. Methods: A cross-sectional study was conducted on a sample of 92 randomly selected diabetic patients. An electrocardiogram was performed, which when it was negative for ischaemia, an exercise stress test or a dobutamine stress echocardiogram was performed. Results: The mean age of the participants was 57 years, 88% of whom were women. The mean duration of the diabetes was 7 years. Asymptomatic ischaemic heart disease was found in 22.8% of case. No significant associations were found between ischaemic heart disease and age, gender, peripheral arterial disease, body mass index, ankle-brachial index, arterial hypertension, dyslipidaemia, active smoking, sedentarism, overweight/obesity, alcoholism, fasting glucose, glycosylated haemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, creatinine, glomerular filtration rate, and urine microalbumin. Conclusions: The prevalence of asymptomatic ischaemic heart disease was 22.8% in the population studied with type 2 diabetes mellitus. No significant associations were found between ischaemic heart disease and the variables studied.

Worse renal outcome of subclass IV-G lupus nephritis patients over IV-S.

Background International Society of Nephrology/ Renal Pathology Society (ISN/RPS) consensus on the classification of lupus nephritis (LN) subdivided class IV into diffuse segmental (IV-S) and diffuse global (IV-G). Nephrologists and nephropathologists believe that this subclassification would be clinically relevant based on hypothetical distinct immunopathogenesis of those subclasses guiding therapy as well as judging prognosis. Methods All adult patients with a renal biopsy-confirmed diagnosis of LN class IV undergoing regular follow-up in the Nephrology Division between January 2004 and December 2014 were enrolled excluding those with diabetes, hepatitis B, hepatitis C, HIV as well as those with insufficient clinical and hystopathological data. Biopsies were reviewed and reclassified according to ISN/RPS 2003 classification by two experienced pathologists and were examined by light microscopy and direct immunofluorescence. Results On baseline subclass IV-G compared to IV-S showed higher frequency of males and histologically higher activity (7.5 ± 2.8 vs 5.1 ± 2.3, p = 0.004) and chronicity index (3.4 ± 1.6 vs 2.4 ± 1.8, p = 0.016) as well as a higher percentage of epithelial crescents (12.9 vs 5.1, p = 0.0001) and vessel abnormalities (72% vs 42%, p = 0.017). Although renal function on baseline was not different between subclasses, IV-G showed lower levels, although not significant, of estimated glomerular filtration based on CKD-EPI formula (91.0 ± 34.8 vs 64.4 ± 44.5, p = 0.059) at the end of follow-up. In addition, we observed a higher rate of patients reaching CKD-EPI under 60 mL/min/1.73 m2 in subclass IV-G over IV-S on last follow-up. Conclusion Subclasses IV-S and IV-G patients show some clinical and pathological differences that might represent distinct stages of the same disease and they should thus be treated the same.

Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge

Among the novel class of endogenous long non-coding RNAs, circular RNA (circRNA) is known as a key regulator in the development and progression of different cancers. Its function and mechanism in the tumorigenesis of colorectal cancer, however, has not been well studied. This study thus aimed to investigate potential regulation of colorectal cancer by circRNAs and the corresponding regulatory mechanism. We demonstrated that the expression of circRNA hsa_circ_0000523 (also known as circ_006229) was down-regulated in different colorectal cancer cell lines. It was also found that interference of hsa_circ_0000523 induced proliferation and suppressed apoptosis of colorectal cancer cells, the proliferation rate of which was reduced by the overexpression of hsa_circ_0000523. In addition, we found that miR-31 could recognize hsa_circ_0000523 sequence and that it acted as a "sponge" of miR-31, indirectly regulating Wnt/β-catenin signaling pathway, which was involved in the progression of colorectal cancer. The results suggested that the expression of hsa_circ_0000523 correlated to the tumorigenesis of colorectal cancer cells. In addition, as a sponge of miR-31, the low level of hsa_circ_0000523 led to activation of Wnt/β-catenin signaling pathway, inducing the subsequent progress of colorectal cancer.

Tissue distribution and early developmental expression patterns of aldolase A, B, and C in grass carp Ctenopharyngodon idellus.

Aldolase is a key enzyme involved in glycolysis, gluconeogenesis, and the pentose phosphate pathway. To establish the expression patterns of all three aldolase isozyme genes in different tissues and during early embryogenesis in lower vertebrates, as well as to explore the functional differences between these three isozymes, the grass carp was selected as a model owing to its relatively high glucose-metabolizing capability. Based on the cDNA sequences of the aldolase A, B, and C genes, the expression patterns of these three isozymes were analyzed in different tissues and during early embryogenesis using quantitative real-time polymerase chain reaction (qRT-PCR). Sequence analysis of cDNAs indicated that aldolase A, B, and C (GenBank accession numbers: KM192250, KM192251, and KM192252) consist of 364, 364, and 363 amino acids, respectively. The qRT-PCR results showed that the expression levels of aldolase A, B, and C were highest in the muscle, liver, and brain, respectively. Aldolase A and C exhibited similar expression patterns during embryogenesis, with high levels observed in unfertilized and fertilized eggs and at the blastocyst stage, followed by a decline and then increase after organogenesis. In contrast, aldolase B transcript was not detected during the unfertilized egg stage, and appeared only from gastrulation; the expression increased markedly during the feeding period (72 h after hatching), at which point the level was higher than those of aldolase A and C. These data suggest that the glucose content of grass carp starter feed should be adjusted according to the metabolic activity of aldolase B.

Antiviral activity of shikonin ester derivative PMM-034 against enterovirus 71 in vitro.

Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 µg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1ß, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.

Nramp1 gene expression in different tissues of Meishan piglets from newborn to weaning.

Natural resistance-associated macrophage protein gene 1 (Nramp1) plays an important role in the innate immune response of swine, and is believed to influence disease resistance. In this study, a real-time quantitative polymerase chain reaction technique was used to investigate Nramp1 expression in 12 different tissues in newborn and 7-, 14-, 21-, 28-, and 35-day-old Meishan piglets. Results indicated that Nramp1 was expressed to varying degrees in all sample tissues, although expression differed among growth stages. For example, Nramp1 was highly expressed in the spleen, but minimally expressed in heart, liver, and muscle tissues among the various piglet age classes. Overall, Nramp1 expression increased with age, reaching significant levels in 21- and 28-day-old animals. Nramp1 was expressed in all 12 tissues tested; however, expression in spleen, lung, kidney, and thymus tissues was highest among newborns, which is consistent with this gene's role in innate immunity improvement. Before and after weaning, Nramp1 was highly expressed in digestive (stomach) and intestinal (duodenum, jejunum, and ileum) tissues, further indicating a genetic role in both immune regulation to compensate for weaning stress and enhanced development of intestinal immunity.

Study on the effects of blueberry treatment on histone acetylation modification of CCl4-induced liver disease in rats.

The objective of this study was to investigate the effects of blueberry treatment on histone acetylation modification of carbon tetrachloride (CCl4)-induced liver disease in rats. Laboratory rats were randomly divided into control, hepatic fibrosis, blueberry treatment, blueberry intervention, and natural recovery groups. Rats in the model groups were treated with CCl4 administered subcutaneously at 4- and 8-week intervals, and then executed. Both the 4- and 8-week treatment groups were treated with blueberry juice for 8 weeks, and then executed after 12 and 16 weeks, respectively. Following the experiment, four liver function and hepatic fibrosis indices were measured. Liver index was calculated, hematoxylin-eosin staining was conducted, and H3K9, H3K14, and H3K18 expressions were evaluated among the nuclear proteins of the liver tissues. No differences in alanine transaminase were noted between the control and intervention groups, but significant differences were detected among the model, treatment, and natural recovery groups (P < 0.01). Significant differences were also observed in aspartate transaminase, hyaluronic acid, and collagen IV among the model, treatment, intervention, and natural recovery groups (P < 0.01, P < 0.01, P < 0.01). Liver index, and H3K9 and H3K14 expression were significantly different among the model groups (P < 0.05 and P < 0.01), whereas H3K18 expression was dramatically different among model, treatment, intervention, and natural recovery groups (P < 0.01). Following blueberry treatment, rat liver function and hepatic fibrosis improved, potentially indicating that blueberry components could regulate histone acetylation and improve liver pathologic changes in rats with CCl4-induced disease.

Antiviral activity of shikonin ester derivative PMM-034 against enterovirus 71 in vitro

Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 μg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1β, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.

Activation of p38-mitogen-activated protein kinase contributes to ischemia reperfusion in rat brain.

Inflammation plays an important role in cerebral ischemia reperfusion, which can cause severe damage to the brain and may lead to cerebral hemorrhage transformation. p38-mitogen-activated protein kinase (p38mapk) has been implicated in the etiology of a number of diseases because it is a cause of inflammation, but comparatively little research has been carried out into its role in the etiology of ischemia reperfusion. We investigated the expression of p38mapk in cerebral ischemia reperfusion to gain a better understanding of its potential role in hemorrhagic transformation (HT). One hundred rats were randomly divided into three groups: an ischemia reperfusion group, an ischemia group, and a sham-operated group. We carried out neurological deficit assessments, infarct volume measurements, histopathological examinations, and immunohistochemistry analyses. p38mapk was overexpressed in the ischemia reperfusion group, which exhibited severe tissue damage and greater edema than the other two groups. These results suggest that p38mapk plays an important role in cerebral ischemia reperfusion, and may be one of the causes of HT.