Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. METHODS: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. DISCUSSION: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].

A PTP1B-Cdk3 Signaling Axis Promotes Cell Cycle Progression of Human Glioblastoma Cells through an Rb-E2F Dependent Pathway.

PTP1B plays a key role in developing different types of cancer. However, the molecular mechanism underlying this effect is unclear. To identify molecular targets of PTP1B that mediate its role in tumorigenesis, we undertook a SILAC-based phosphoproteomic approach, which allowed us to identify Cdk3 as a novel PTP1B substrate. Substrate trapping experiments and docking studies revealed stable interactions between the PTP1B catalytic domain and Cdk3. In addition, we observed that PTP1B dephosphorylates Cdk3 at tyrosine residue 15 in vitro and interacts with it in human glioblastoma cells. Next, we found that pharmacological inhibition of PTP1B or its depletion with siRNA leads to cell cycle arrest with diminished activity of Cdk3, hypophosphorylation of Rb, and the downregulation of E2F target genes Cdk1, Cyclin A, and Cyclin E1. Finally, we observed that the expression of a constitutively active Cdk3 mutant bypasses the requirement of PTP1B for cell cycle progression and expression of E2F target genes. These data delineate a novel signaling pathway from PTP1B to Cdk3 required for efficient cell cycle progression in an Rb-E2F dependent manner in human GB cells.

Circulating miRNAs as Noninvasive Biomarkers for PDAC Diagnosis and Prognosis in Mexico.

Among malignant neoplasms, pancreatic ductal adenocarcinoma (PDAC) has one of the highest fatality rates due to its late detection. Therefore, it is essential to discover a noninvasive, early, specific, and sensitive diagnostic method. MicroRNAs (miRNAs) are attractive biomarkers because they are accessible, highly specific, and sensitive. It is crucial to find miRNAs that could be used as possible biomarkers because PDAC is the eighth most common cause of cancer death in Mexico. With the help of microRNA microarrays, differentially expressed miRNAs (DEmiRNAs) were found in PDAC tissues. The presence of these DEmiRNAs in the plasma of Mexican patients with PDAC was determined using RT-qPCR. Receiver operating characteristic curve analysis was performed to determine the diagnostic capacity of these DEmiRNAs. Gene Expression Omnibus datasets (GEO) were employed to verify our results. The Prisma V8 statistical analysis program was used. Four DEmiRNAs in plasma from PDAC patients and microarray tissues were found. Serum samples from patients with PDAC were used to validate their overexpression in GEO databases. We discovered a new panel of the two miRNAs miR-222-3p and miR-221-3p that could be used to diagnose PDAC, and when miR-221-3p and miR-222-3p were overexpressed, survival rates decreased. Therefore, miR-222-3p and miR-221-3p might be employed as noninvasive indicators for the diagnosis and survival of PDAC in Mexican patients.

p21 Activated kinase 1: Nuclear activity and its role during DNA damage repair.

p21-activated kinase 1 (PAK1) is a serine/threonine kinase activated by the small GTPases Rac1 and Cdc42. It is located in the chromosome 11q13 and is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors. This enzyme plays a pivotal role in the control of a number of fundamental cellular processes by phosphorylating its downstream substrates. In addition to its role in the cytoplasm, it is well documented that PAK1 also plays crucial roles in the nucleus participating in mitotic events and gene expression through its association and/or phosphorylation of several transcription factors, transcriptional co-regulators and cell cycle-related proteins, including Aurora kinase A (AURKA), polo-like kinase 1 (PLK1), the forkhead transcription factor (FKHR), estrogen receptor α (ERα), and Snail. More recently, PAK signaling has emerged as a component of the DNA damage response (DDR) as PAK1 activity influences the cellular sensitivity to ionizing radiation and promotes the expression of several genes involved in the Fanconi Anemia/BRCA pathway. This review will focus on the nuclear functions of PAK1 and its role in the regulation of DNA damage repair.

Obesidad infantil: factor de riesgo para desarrollar pie plano / Childhood obesity: a risk factor for development of flatfoot

Introducción: En México, la prevalencia de sobrepeso y obesidad en escolares es del 34.4% (ENSANUT 2012). Esta puede inducir un círculo vicioso "pie plano-plantalgia-sedentarismo-obesidad". Sin embargo, la presencia y grado de pie plano en escolares con obesidad no se ha descrito en la población mexicana. El objetivo del estudio fue determinar la prevalencia de pie plano y su asociación con obesidad en escolares de Tamaulipas, México. Métodos: Se realizó un estudio analítico, transversal con 1,128 escolares de 9 a 11 años de edad, de los cuales el 48.8% correspondió al sexo masculino (H) y el 51.2% al femenino (M). Se realizaron mediciones antropométricas (peso, talla, perímetro de cintura y cadera). Se calculó el índice de masa corporal (IMC) y se consideró como obesidad cuando el IMC fue mayor del percentil 95. Se fotografió la huella plantar por medio de un podoscopio, utilizando la clasificación de Denis para diagnosticar los grados de pie plano. Resultados: La prevalencia de sobrepeso-obesidad fue del 49.1% y de pie plano fue del 12.1% (H: 8.1%, M: 4%; p = 0.28). La asociación entre obesidad y pie plano fue significativa (p <0.001) y con un riesgo 2.5 veces mayor en los niños con sobrepeso-obesidad en comparación con los de peso normal. Conclusiones: Existe una asociación entre la obesidad y el pie plano, por lo que se sugiere implementar medidas de prevención secundaria en la población.

Background: In Mexico, the prevalence of overweight and obesity is 34.4% in school-age children (ENSANUT 2012), which may induce a vicious cycle of flatfoot-plantalgia-sedentarism-obesity, although the presence and degree of flatfoot in school-age children with obesity has not yet been described in a Mexican population. The objective of the study was to determine the prevalence of flatfoot and its association with obesity in school-age children living in Tampico. Methods: An analytical and cross-sectional study with 1128 students, 48.8% male and 51.2% female, 9- to 11-years of age. Anthropometric measurements (weight and height) were performed. Body mass index (BMI) was calculated and obesity was considered a BMI percentile >95. Plantar footprint was photographed via a podoscope using Denis classification to diagnose flatfoot grades. Results: The prevalence of overweight/obesity was 49.1% and of flatfoot was 12.1% (male: 8.1%, female: 4%, p = 0.28). The association between obesity and flatfoot was significant (p <0.001) and there was a 2.5 times higher risk of overweight-obese children compared to those of normal weight. Conclusions: There is an association between obesity and flatfoot. We suggest implementing secondary prevention measures in this population.

[Childhood obesity: a risk factor for development of flatfoot]. / Obesidad infantil: factor de riesgo para desarrollar pie plano.

BACKGROUND: In Mexico, the prevalence of overweight and obesity is 34.4% in school-age children (ENSANUT 2012), which may induce a vicious cycle of flatfoot-plantalgia-sedentarism-obesity, although the presence and degree of flatfoot in school-age children with obesity has not yet been described in a Mexican population. The objective of the study was to determine the prevalence of flatfoot and its association with obesity in school-age children living in Tampico. METHODS: An analytical and cross-sectional study with 1128 students, 48.8% male and 51.2% female, 9- to 11-years of age. Anthropometric measurements (weight and height) were performed. Body mass index (BMI) was calculated and obesity was considered a BMI percentile >95. Plantar footprint was photographed via a podoscope using Denis classification to diagnose flatfoot grades. RESULTS: The prevalence of overweight/obesity was 49.1% and of flatfoot was 12.1% (male: 8.1%, female: 4%, p = 0.28). The association between obesity and flatfoot was significant (p <0.001) and there was a 2.5 times higher risk of overweight-obese children compared to those of normal weight. CONCLUSIONS: There is an association between obesity and flatfoot. We suggest implementing secondary prevention measures in this population.