Resveratrol Alleviates Osteoporosis by Promoting Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells via SITR1/PI3K/AKT Pathway / El Resveratrol Alivia la Osteoporosis al Promover la Diferenciación Osteogénica de las Células Madre Mesenquimales de la Médula Ósea a Través de la Vía SITR1/PI3K/AKT

SUMMARY: Senile osteoporosis is mainly caused by reduced osteoblast differentiation and has become the leading cause of fractures in the elderly worldwide. Natural organics are emerging as a potential option for the prevention and treatment of osteoporosis. This study was designed to study the effect of resveratrol on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in osteoporosis mice. A mouse model of osteoporosis was established by subcutaneous injection of dexamethasone and treated with resveratrol administered by gavage. In vivo and in vitro, we used western blot to detect protein expression, and evaluated osteogenic differentiation of BMSCs by detecting the expression of osteogenic differentiation related proteins, calcium deposition, ALP activity and osteocalcin content. Resveratrol treatment significantly increased the body weight of mice, the level of serum Ca2+, 25(OH)D and osteocalcin, ration of bone weight, bone volume/total volume, trabecular thickness, trabecular number, trabecular spacing and cortical thickness in osteoporosis mice. In BMSCs of osteoporosis mice, resveratrol treatment significantly increased the expression of Runx2, osterix (OSX) and osteocalcin (OCN) protein, the level of calcium deposition, ALP activity and osteocalcin content. In addition, resveratrol treatment also significantly increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT in BMSCs of osteoporosis mice. In vitro, resveratrol increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT, Runx2, OSX and OCN protein, the level of calcium deposition, ALP activity and osteocalcin content in BMSCs in a concentration-dependent manner, while SIRT1 knockdown significantly reversed the effect of resveratrol. Resveratrol can attenuate osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells, and the mechanism may be related to the regulation of SIRT1/PI3K/AKT pathway.

La osteoporosis senil es causada principalmente por una diferenciación reducida de osteoblastos y se ha convertido en la principal causa de fracturas en las personas mayores en todo el mundo. Los productos orgánicos naturales están surgiendo como una opción potencial para la prevención y el tratamiento de la osteoporosis. Este estudio fue diseñado para estudiar el efecto del resveratrol en la diferenciación osteogénica de las células madre mesenquimales de la médula ósea (BMSC) en ratones con osteoporosis. Se estableció un modelo de osteoporosis en ratones mediante inyección subcutánea de dexametasona y se trató con resveratrol administrado por sonda. In vivo e in vitro, utilizamos Western blot para detectar la expresión de proteínas y evaluamos la diferenciación osteogénica de BMSC detectando la expresión de proteínas relacionadas con la diferenciación osteogénica, la deposición de calcio, la actividad de ALP y el contenido de osteocalcina. El tratamiento con resveratrol aumentó significativamente el peso corporal de los ratones, el nivel sérico de Ca2+, 25(OH)D y osteocalcina, la proporción de peso óseo, el volumen óseo/ volumen total, el espesor trabecular, el número trabecular, el espaciado trabecular y el espesor cortical en ratones con osteoporosis. En BMSC de ratones con osteoporosis, el tratamiento con resveratrol aumentó significativamente la expresión de las proteínas Runx2, osterix (OSX) y osteocalcina (OCN), el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina. Además, el tratamiento con resveratrol también aumentó significativamente la expresión de SIRT1, p-PI3K/PI3K y p-AKT/AKT en BMSC de ratones con osteoporosis. In vitro, el resveratrol aumentó la expresión de las proteínas SIRT1, p-PI3K/PI3K y p- AKT/AKT, Runx2, OSX y OCN, el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina en BMSC de manera dependiente de la concentración, mientras que La caída de SIRT1 revirtió significativamente el efecto del resveratrol. El resveratrol puede atenuar la osteoporosis al promover la diferenciación osteogénica de las células madre mesenquimales de la médula ósea, y el mecanismo puede estar relacionado con la regulación de la vía SIRT1/PI3K/AKT.

Influence of the addition of nanohydroxyapatite to scaffolds on proliferation and differentiation of human mesenchymal stem cells: a systematic review of in vitro studies

One of the main challenges of tissue engineering in dentistry is to replace bone and dental tissues with strategies or techniques that simulate physiological tissue repair conditions. This systematic review of in vitro studies aimed to evaluate the influence of the addition of nanohydroxyapatite (NHap) to scaffolds on cell proliferation and osteogenic and odontogenic differentiation of human mesenchymal stem cells. In vitro studies on human stem cells that proliferated and differentiated into odontogenic and osteogenic cells in scaffolds containing NHap were included in this study. Searches in PubMed/MEDLINE, Scopus, Web of Science, OpenGrey, ProQuest, and Cochrane Library electronic databases were performed. The total of 333 articles was found across all databases. After reading and analyzing titles and abstracts, 8 articles were selected for full reading and extraction of qualitative data. Results showed that despite the large variability in scaffold composition, NHap-containing scaffolds promoted high rates of cell proliferation, increased alkaline phosphatase (ALP) activity during short culture periods, and induced differentiation, as evidenced by the high expression of genes involved in osteogenesis and odontogenesis. However, further studies with greater standardization regarding NHap concentration, type of scaffolds, and evaluation period are needed to observe possible interference of these criteria in the action of NHap on the proliferation and differentiation of human stem cells.

Fibroblasts inhibit osteogenesis by regulating nuclear-cytoplasmic shuttling of YAP in mesenchymal stem cells and secreting DKK1

Background Fibrous scars frequently form at the sites of bone nonunion when attempts to repair bone fractures have failed. However, the detailed mechanism by which fibroblasts, which are the main components of fibrous scars, impede osteogenesis remains largely unknown. Results In this study, we found that fibroblasts compete with osteogenesis in both human bone nonunion tissues and BMP2-induced ectopic osteogenesis in a mouse model. Fibroblasts could inhibit the osteoblastic differentiation of mesenchymal stem cells (MSCs) via direct and indirect cell competition. During this process, fibroblasts modulated the nuclear-cytoplasmic shuttling of YAP in MSCs. Knocking down YAP could inhibit osteoblast differentiation of MSCs, while overexpression of nuclear-localized YAP-5SA could reverse the inhibition of osteoblast differentiation of MSCs caused by fibroblasts. Furthermore, fibroblasts secreted DKK1, which further inhibited the formation of calcium nodules during the late stage of osteogenesis but did not affect the early stage of osteogenesis. Thus, fibroblasts could inhibit osteogenesis by regulating YAP localization in MSCs and secreting DKK1. Conclusions Our research revealed that fibroblasts could modulate the nuclear-cytoplasmic shuttling of YAP in MSCs, thereby inhibiting their osteoblast differentiation. Fibroblasts could also secrete DKK1, which inhibited calcium nodule formation at the late stage of osteogenesis.

Research progress of nitrobenzoyl sesquiterpenoids as marine characteristic natural products / 药学学报

Sesquiterpenoids are widely found in nature, while nitrobenzoyl sesquiterpenoids are relatively rare. Twelve natural nitrobenzoyl sesquiterpenoids were all derived from marine Aspergillus fungi, which are typical natural products with marine characteristics. These natural products exhibit good antitumor, antiviral, and inhibition of osteoclast differentiation activity, especially in the treatment of osteoclast-related diseases, showing good medicinal development value. This article reviews the natural product sources, chemical structure, chemical synthesis, biosynthesis, bioactivity, and pharmacological mechanisms of nitrobenzoyl sesquiterpenoids and predicts and discusses their absorption, distribution, metabolism, excretion, toxicity (ADME/T), and drug-likeness, providing a comprehensive understanding of the natural products of nitrobenzoyl sesquiterpenoids from marine sources and their potential for pharmaceutical development.

Exploration of Decision-Making Methods Based on Syndrome Differentiation by “Data-Knowledge” Dual-Driven Models： A Case Study of Gastric Precancerous State / 中医杂志

Data analysis models may assist the transmission of traditional Chinese medicine （TCM） experience and clinical diagnosis and treatment， and the possibility of constructing a “data-knowledge” dual-drive model was explored by taking gastric precancerous state as an example. Data-driven is to make clinical decisions around data analysis， and its syndrome-differentiation decision-making research relies on hidden structural models and partially observable Markov decision-making processes to identify the etiology of diseases， syndrome elements， evolution of pathogenesis， and syndrome differentiation protocols； knowledge-driven is to make use of data and information to promote decision-making and action processes， and its syndrome-differentiation decision-making research relies on convolutional neural networks to improve the accuracy of local disease identification and syndrome differentiation. The “data-knowledge” dual-driven model can make up for the shortcomings of single-drive numerical simulation accuracy， and achieve a balance between local disease identification and macroscopic syndrome differentiation. On the basis of previous research， we explored the construction method of diagnostic assisted decision-making platform for gastric precancerous state， and believed that the diagnostic and decision-making ability of doctors can be extended through the assistance of machines and algorithms. Meanwhile， the related research methods were integrated and the core features of gastric precancerous state based on TCM syndrome differentiation and endoscopic pathology diagnosis and prediction were obtained， and the elements of endoscopic pathology recognition based on TCM syndrome differentiation were explored， so as to provide ideas for the in-depth research and innovative application of cutting-edge data analysis technology in the field of intelligent TCM syndrome differentiation.

Construction of a Three-dimensional Syndrome Differentiation System for Pulmonary Nodules under the Perspective of Qi， Blood and Fluids / 中医杂志

Based on the theory of qi， blood and fluids， and taking into account of the pathogenesis evolution process from constraint to phlegm， stasis and then mass in pulmonary nodules， an attempt has been made to construct a three-dimensional differentiation system for pulmonary nodules from the dimensions of time and space. The temporal progression of the early， middle， and late stages of pulmonary nodules reflects the pathological changes from constraint to phlegm and then stasis in the metabolism disorders of qi， blood and fluid. The spatial structures such as size， density， and morphology of pulmonary nodules reflect the pathological states of the duration， severity， and primary and secondary conditions of qi， blood and fluid metabolism disorders. Based on the temporal progression， the therapeutic principles have been proposed， which are dispelling pathogenic factors and promoting the use of beneficial factors to interrupt the growth momentum in the early stage， removing turbidity and dispersing phlegm to reduce the degree of nodules in the middle stage， and dispersing nodulation and eliminating abnormalities in the late stage. Based on the spatial structures， the suggested therapeutic methods are using wind herbs， employing multiple approaches to treat phlegm， and promoting blood circulation to resolve stasis， so as to provide theoretical reference for the systematic diagnosis and treatment of pulmonary nodules in traditional Chinese medicine.

Traditional Chinese Medicine Syndromes in Depressive Episodes of Bipolar Disorder Based on Cluster Analysis and Bayesian Network：A Cross-sectional Study / 中医杂志

ObjectiveTo explore the elements， distribution and characteristics of traditional Chinese medicine （TCM） syndromes in depressive episodes of bipolar disorder （BD）. MethodsBasic information， along with the four examination information， the Hamilton Depression Scale and Young Mania Rating Scale scores， were collected from 293 outpatients with BD at Beijing Anding Hospital， Capital Medical University. The four examination information with an occurrence rate greater than 12% were retained. The R language “dist” function was used to calculate the distances between samples using the Euclidean distance method. The hierarchical clustering of the four examination information was performed using the “hclust” function and the squared Euclidean distance method. A team of five researchers was formed to determine the nature and location of the essential elements of TCM syndrome in BD based on the clustering results. The PC algorithm was used to construct a Bayesian network model of the essential elements. The working group combined the essential elements of TCM syndromes in the Bayesian network according to the reference model results， and then extracted common TCM syndromes. The score of each patient based on the essential elements was matched with the common TCM syndromes to determine the syndrome type of each patient. The working group then performs conformity and revision based on this， obtaining the final distribution of TCM syndromes for the patients. ResultsThere were 77 common TCM symptoms in BD with a frequency greater than 12%. The top 15 symptoms with higher frequencies were slippery pulse， mental fatigue and lack of strength， wiry pulse， excessive rumination， preference for solitude， vexation， agitation and irritability， dry mouth， palpitations， profuse dreaming， unwarranted worries， chest oppression， thin white coating， amnesia， frequent sighing， and poor appetite. TCM syndrome elements of BD can be grouped into 11 categories. The nature of disease-related essential elements included fire， qi deficiency， blood deficiency， qi counterflow， yin deficiency， dampness， heat， fire from constraint， and phlegm. The location of disease-related essential elements included heart， liver， spleen， stomach， kidney， bladder channel， and gallbladder. By constructing a Bayesian network model and considering the opinions from the experts， six common syndromes of BD were identified， among which the highest proportion was heart-stomach heat accumulation， accounting for 27.99% （82 cases）， followed by heart-spleen deficiency （55 cases， 18.77%）， non-interaction between the heart and the kidney （49 cases， 16.72%）， liver constraint and blood deficiency （42 cases， 14.33%）， heart qi deficiency （37 cases， 12.63%）， and damp-heat in the liver and gallbladder （28 cases， 9.56%）. ConclusionsThe nature of disease-related elements of BD are predominantly fire and heat， while the location of disease-related essential elements are primarily associated with the heart， liver， and spleen. The most common TCM syndromes are heart-stomach heat accumulation and heart-spleen deficiency.

Exploration of Role of Yin and Yang Syndrome Differentiation in Parkinson's Disease / 中国实验方剂学杂志

The syndrome differentiation of Yin and Yang has the function of controlling the other six principles in the eight principles syndrome differentiation，which is a higher level or general induction of the disease. In the clinical process of traditional Chinese medicine，syndrome differentiation of Yin and Yang runs through the whole process of disease diagnosis and treatment. For Parkinson's disease，syndrome differentiation of Yin and Yang is particularly important. Different symptoms，the transformation of pathogenesis during the development of the disease and the treatment of traditional Chinese and western medicine all reflect the characteristics of Yin and Yang opposition restriction，mutual root and mutual use，and the transformation of ebb and flow. This article discusses the background，application and value of Yin-Yang syndrome differentiation from three aspects：the origin and application of yin-yang syndrome differentiation，the basis of Parkinson's disease syndrome differentiation，and the status and role of Yin-Yang syndrome differentiation in Parkinson's disease. It is of great significance to guide the diagnosis and treatment of Parkinson's disease with "Yin-Yang as the key point".

Potential of human induced pluripotent stem cells differentiating into corneal epithelial cells in simulated limbal stem cell microenvironment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the potential of human induced pluripotent stem cells(hiPSCs)differentiating into corneal epithelial cells in the simulated limbal stem cells(LSCs)microenvironment.METHODS: The hiPSC cell lines were established in vitro, and hiPSCs were co-cultured with corneal stromal cells in transwell system, which simulated the LSC microenvironment. Bone morphogenetic protein 4(BMP4)and a specific transforming growth factor β inhibitor(SB431542)were added to improve the differentiation efficacy. The expression of corneal epithelial cell-specific markers CK3 and CK12, corneal epithelial cell precursor CK15, and the limbal stem cell markers ABCG5 were determined by immunofluorescence staining and flow cytometry.RESULTS: The hiPSCs were actively proliferated in vitro, and immunofluorescence staining showed positive stem cell-specific markers OCT4, SOX2, TRA-1-60 and NANOG. Furthermore, hiPSCs co-cultured with corneal stromal cells exhibited LSCs markers ABCG5 and corneal epithelial cell precursor markers CK15 were positive; however, corneal epithelial cell markers CK3 and CK12 were negative. With the addition of BMP4 and SB431542, hiPSCs showed positive expression of CK3, and the CK3 expression increased over the time.CONCLUSION: With the addition of SB431542 and BMP4, hiPSCs cultured in simulated LSCs microenvironment could differentiate into corneal epithelial cells.

Effect of low concentration of sodium fluoride on osteogenic/odontogenic differentiation of human dental pulp cells / 口腔疾病防治

Objective@#To study the effect of low concentrations of sodium fluoride on the osteogenic/odontogenic differentiation of human dental pulp cells (hDPCs) in vitro.@*Methods@#This study was reviewed and approved by the Ethics Committee. hDPCs were cultured using a modified tissue explant technique in vitro. The effects of different concentrations of sodium fluoride on the proliferation of hDPCs were measured by methylthiazol tetrazolium (MTT) assay. Appropriate concentrations were added to the osteogenic/odontogenic differentiation induction medium, and the cells were induced in vitro. Alizarin red S staining was used to detect the osteoblastic/odontogenic differentiation ability of the cells, and the mRNA expression of the key differentiation factors was detected by RT-qPCR. Moreover, the expression of key molecules of endoplasmic reticulum stress (ERS) was detected by RT-qPCR and Western blot. The data were analyzed with the SPSS 18.0 software package.@*Results@#Low concentration of NaF (0.1 mmol/L) could stimulate cell proliferation in vitro, while a high concentration (5-10 mmol/L) could inhibit cell proliferation (P<0.05). According to the literature and the experimental data, 0.1 mmol/L NaF was selected as the following experimental concentration. The levels of alizarin red S staining were increased after NaF induction of mixed osteogenic/odontogenic differentiation in vitro. The mRNA expression levels of key molecules for osteogenic/odontogenic differentiation, dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP) and osteocalcin (OCN), were increased (P<0.05). The mRNA levels of ERS markers (splicing x-box binding protein-1 (sXBP1), glucose-regulated protein 78 (GRP78) and activating transcription Factor 4 (ATF4) were increased in NaF-treated cells. The protein expression levels of key ER stress molecules (phosphorylated RNA-activated protein kinase-like ER-resident kinase (p-PERK), phosphorylated eukaryotic initiation factor-2α (p-eIF2α) and ATF4) were higher in NaF-treated cells.@*Conclusion@#A low concentration of NaF promotes the osteogenic/odontogenic differentiation of hDPCs and increases the level of ER stress.

Formation of Hyperprogression of Immunotherapy from Perspective of "Yang Deficiency and Toxin Knot" and Role of "Five Views on Differentiation and Treatment" Intervention / 中国实验方剂学杂志

Immune checkpoint inhibitors （ICIs） have shown good efficacy in tumor treatment and have changed the landscape of tumor treatment. However， some patients treated with ICIs have not only failed to achieve the desired therapeutic effect， but also developed an atypical response pattern of abnormally accelerated tumor growth， namely hyperprogressive disease （HPD）. The pathogenesis of HPD is still unclear and it is difficult to diagnose， which poses a challenge for clinical identification and treatment decisions. Exploring the underlying mechanism of HPD is important to improve the effect of immunotherapy. Based on the theory of "Yang deficiency and toxic knot"， this paper discussed the mechanism of HPD in immunotherapy from the perspective of "spleen and kidney Yang deficiency and hefty toxic pathogens". It was concluded that the inactivation of p53 oncogene and immunosuppressive microenvironment were the manifestations of the deficiency of healthy qi in the body and declined yang in the spleen and kidney， serving as an important basis for the occurrence of HPD. Adverse reactions caused by ICIs belong to the category of "drug toxicity". The occurrence and development of murine double minute 2 （MDM2）/murine double minute 4 （MDM4） activation， epidermal growth factor receptor （EGFR） mutation， and tumor inflammatory microenvironment are the manifestations of the hyperactivity of pathogenic Qi， conflict of cancer toxicity and drug toxicity， and being hefty by virtue of deficiency， which can promote the abnormal proliferation of tumor cells， and they are the core pathogenic elements of HPD and are closely related to disease prognosis. In terms of treatment， under the guidance of the theory of "five views on differentiation and treatment" （time-space view， core view， symptom view， precision view， and disease-before-onset view）， which was summarized according to the clinical practice of this research team， this paper， taking the prevention and treatment of HPD as the entry point， formulated traditional Chinese medicine （TCM） compounds to reinforce healthy Qi and warm Yang and realize the dynamic management of the whole spatiotemporal cycle， and removed toxins and resisted cancer to realize the all-round systemic intervention of the specimen. Additionally， targets were enriched in the macro-clinical manifestations and microscopic pathological changes of HPD to improve the targeting of drug selection and the precision of prevention and treatment， giving full play to the unique therapeutic advantages of TCM， and providing new ideas for the clinical application of TCM in the prevention and treatment of HPD.

Relación entre diferenciación del self y agresión entre pares en estudiantes universitarios argentinos / Relationship between Differentiation of Self and Peer Aggression among Argentine University Students

Resumen La agresión entre pares, sea un caso aislado o recurrente, se ha convertido en un problema cada vez más frecuente que socava el desarrollo psicoafectivo saludable en adolescentes y universitarios. Como en el caso de otras conductas de riesgo, la investigación sugiere que los aspectos emocionales son relevantes para su prevención. El objetivo de este trabajo fue explorar la posible relación entre la agresión entre pares, la agresión frecuente como potencial conducta de bullying, y la diferenciación del self, un constructo procedente de la perspectiva sistémica, vinculado con la autorregulación emocional y la madurez afectiva. Universitarios de entre 17 y 20 años (. = 365), completaron sendos cuestionarios autoadministrados sobre estilos de vida (Carlos et al., 2016) y diferenciación del self (Duch-Ceballos et al., 2022). En esta muestra, los análisis realizados indican que menores niveles de diferenciación del self en los varones se asocian con mayor probabilidad de agresión entre pares, tanto sufrida como ejercida. Además, uno de los componentes de la diferenciación del self, la reactividad emocional, predijo también las probabilidades de agresión (sufrida y ejercida) entre las mujeres. La diferenciación del self está recibiendo una creciente atención como variable relevante para explicar la conducta de los adolescentes y jóvenes emergentes, especialmente en lo que refiere a conductas de riesgo. Este sería el primer estudio sobre la relación entre diferenciación del self, agresión entre pares y agresión frecuente como potencial conducta de buylling. Finalmente, a partir de los resultados encontrados, se plantean futuras líneas de investigación y aplicaciones prácticas.

Abstract The socio-emotional well-being of children and adolescents is a subject of interest, both for academics and researchers, as well as for parents, teachers, and educators. Initiatives on this subject promoted from the scientific and social fields are constantly increasing, and tend to have multiple objectives, among which one is to understand the dynamics of violence and aggression (which can lead to harassment situations), in order to design more effective prevention and intervention programs. Research suggests that emotional aspects are relevant to the prevention of aggression. Within this realm, we have focused on Differentiation of self (DoS). The Differentiation of Self is the central construct of Bowen's (1978) systemic family theory, considered from the systemic perspective as one of the most comprehensive theories of human behavior. With multiple applications in various fields, DoS is a multidimensional construct, defined as the ability to balance emotional and intellectual functioning -intrapsychic dimension-, and intimacy and autonomy in personal relationships -interpersonal dimension-. Based on previous studies in which associations between bullying and socio-emotional competencies were found, the objective of this study was to find relationships between differentiation of self and peer aggression. The sample of this study was comprised of university students between 17 and 20 years old (. = 365; . = 18.3, SD = .7), who were studying the first or second year of different careers at a private university in Argentina. Participants completed self-administered questionnaires on lifestyles (Carlos et al., 2016) and the Spanish version of the Differentiation of Self Inventory-Revised (S-DSI; Rodríguez-González et al., 2015). Considering that peer aggression does not represent bullying in all cases, the association between self-differentiation and peer aggression was first analyzed and, second, this same association was analyzed, but considering frequent aggression. Peer aggression was perpetrated by 54 % of women and 63 % of men (. = .043) and suffered by 72 % of women and 61 % of men (. = .124). Frequent peer aggression was perpetrated by 15 % of women and 21 % of men (. = .001) and suffered by 41 % of women and 24 % of men (. = .146). Both measures of DoS (Emotional reactivity and Emotional cutoff) were associated with a lower prevalence of both aggression and frequent aggression. This work offers two main findings. First, given the high incidence of peer aggression, the results of this study confirm the relevance of the research on peer aggression and, specifically, on frequent aggression associated with bullying. Second, present data suggests the existence of a relationship between differentiation of self and aggression. Since the idea and perceptions about aggression could be changing, new research is suggested, based around the cultural context and social changes that identify how the concept of bullying evolves should be promoted. Moreover, it would be positive to develop new research that can delve into the role played by the differentiation of self, since it is a factor that impacts the development and health of adolescents. The significant relationship between peer aggression and DoS found in this study contributes to the empirical corpus that affirms the relevance of the emotional factor in aggressive and bullying behaviors. In this sense, this study joins others that support the idea of intervening in aggression and buylling through the development of school intervention programs aimed at developing emotional competencies, involving students and also parents and educators.

The B-cell non-Hodgkin’s lymphoma: An enigma to diagnose

Non-Hodgkin’s lymphoma is a heterogeneous group of malignancies characterized by an abnormal clonal proliferation of T-cells, B-cells, or both. Sometimes, tuberculosis and lymphoma presentation can share common symptoms and features. In this case report, we present the case of a 28-year-old female patient who came with a chief complaint of swelling on the right side of the face for the past 6 months. Initially, it was not associated with pain but gradually developed severe pain over the region and reduced salivary flow. The patient was planned for surgery with a differential diagnosis of salivary gland pathology. Post-operatively, the histopathological report showed atypical cells which were diffusely positive for cluster of differentiation (CD)20. Focally positive for CD45 and CD3 which was positive in reactive T lymphocytes. Immunohistochemistry pattern favors the diagnosis of B-cell type NHL. Through this case report, we want to share our experience in treating an aggressive tumor that mimics salivary gland pathology.

An Observational Study on Cutaneous Appendageal Tumours with Pilar Differentiation

Background: Cutaneous appendageal tumours belong to a diverse group of tumours with specific histo pathology.The aim of this study is to determine the pattern, age,gender and site distribution of Pilar differentiation tumours. Material & Methods: The study was conducted in the department of Pathology,Government Medical College Srinagar for a period of 18 months. It was an observational cross sectional study.Formalin fixed,paraffin embedded tissue sections were stained with hematoxylin and eosin stain for histopathological analysis. Results: A total of 112 cases of Pilar tumours were studied.108 were benign and 4 were malignant with male to female ratio of 1.07:1. The maximum number of benign cases were observed in 11 -20 years of age group and the malignant tumours age ranges from 35-45 years and the tumour usually presented in the eighth decade.Head and Neck was the most common site. Conclusion: Histopathological examination of Pilar Tumours is the gold standard to differentiate between benign and malignant tumours. It is also useful for exact categorization of cutaneous appendageal tumours.

A rare case of metastatic malignant phyllodes tumor with osteosarcomatous differentiation presenting with intestinal obstruction

Phyllodes tumors (PTs) are uncommon biphasic breast neoplasms constituting 0.5 to 1.0% of all breast tumors. Malignant PTs form a very small proportion of these and may metastasize, especially to the lungs and bones. Aggression and metastatic potential are accentuated in tumors exhibiting heterologous differentiation. Metastases to the gastrointestinal tract (GIT) have seldom been reported and are often confined to a segment of the digestive tract. In the absence of relevant clinical history, such patients presenting with gastrointestinal symptoms can lead to diagnostic perplexities. We report a unique case of a malignant PT with extensive osteosarcomatous differentiation and widespread metastases to the GIT.

Pineocytoma with malignant transformation to pineal parenchymal tumor with intermediate differentiation and leptomeningeal dissemination after subtotal tumor resection and adjuvant radiotherapy

Pineocytoma is a rare tumor. It is rare for pineocytoma to present as leptomeningeal metastasis. We present a rare case of pineocytoma with malignant transformation and leptomeningeal metastasis after subtotal tumor resection and adjuvant radiotherapy. This case was a 58-year-old male with an unsteady gait for 2 months. Enhanced brain magnetic resonance imaging revealed a heterogeneous mass involving the pineal region. The initial pathological diagnosis of pineocytoma was confirmed after subtotal tumor resection. Two years after adjuvant radiotherapy to the primary site, the magnetic resonance imaging showed C2 and T2 metastatic lesions, with the final pathological diagnosis being pineal parenchymal tumor (PPT) with intermediate differentiation after the removal of T2 intramedullary tumor. After that adjuvant radiotherapy at the cervical and thoracic spinal cord was completed. There was no recurrence of the tumor 1 year after the radiotherapy. We report a rare case of pineocytoma with malignant transformation to PPT with intermediate differentiation and leptomeningeal dissemination.

HISTOLOGICAL VARIANTS OF BLADDER TUMORS : DIAGNOSTIC, PROGNOSTIC AND THERAPEUTIC IMPLICATIONS – A CASE SERIES

Bladder cancer is one of the leading malignancies in the world associated with signi?cant morbidity and mortality. About 80% of a bladder cancer is urothelial variant, remaining 20% will have a divergent histological presentation. The pathophysiological study of these variants has recently increased because the therapeutic approach is not uniform for all variants. These variants have important diagnostic, prognostic and therapeutic implications. A molecular and genetic study of these variants will allow them to be better de?ned. Here we present four cases of Histological variants of bladder tumors with varying presentations in the department of urology, Madurai medical college, which is studied over the period of one year (2022-2023).

NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration

Background Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. Results Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. Conclusions These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.

Characterization of neural stem cells derived from human stem cells from the apical papilla undergoing three-dimensional neurosphere induction

Abstract Objectives The endogenous repairing based on the activation of neural stem cells (NSCs) is impaired by neurodegenerative diseases. The present study aims to characterize human stem cells from the apical papilla (hSCAPs) with features of mesenchymal stem cells (MSCs) and to demonstrate the neuronal differentiation of hSCAPs into NSCs through the formation of three-dimensional (3D) neurospheres, verifying the structural, immunophenotyping, self-renewal, gene expression and neuronal activities of these cells to help further improve NSCs transplantation. Methodology The hSCAPs were isolated from healthy impacted human third molar teeth and characterized as MSCs. They were then induced into 3D-neurospheres using a specific neural induction medium. Subsequently, the intra-neurospheral cells were confirmed to be NSCs by the identification of Nissl substance and the analysis of immunofluorescence staining, self-renewal ability, and gene expression of the cells. Moreover, the neuronal activity was investigated using intracellular calcium oscillation. Results The isolated cells from the human apical papilla expressed many markers of MSCs, such as self-renewal ability and multilineage differentiation. These cells were thus characterized as MSCs, specifically as hSCAPs. The neurospheres induced from hSCAPs exhibited a 3D-floating spheroidal shape and larger neurospheres, and consisted of a heterogeneous population of intra-neurospheral cells. Further investigation showed that these intra-neurospheral cells had Nissl body staining and also expressed both Nestin and SOX2. They presented a self-renewal ability as well, which was observed after their disaggregation. Their gene expression profiling also exhibited a significant amount of NSC markers (NES, SOX1, and PAX6). Lastly, a large and dynamic change of the fluorescent signal that indicated calcium ions (Ca2+) was detected in the intracellular calcium oscillation, which indicated the neuronal activity of NSCs-derived hSCAPs. Conclusions The hSCAPs exhibited properties of MSCs and could differentiate into NSCs under 3D-neurosphere generation. The present findings suggest that NSCs-derived hSCAPs may be used as an alternative candidates for cell-based therapy, which uses stem cell transplantation to further treat neurodegenerative diseases.

The ethics of nursing care for transgender people / A ética do cuidado de enfermagem às pessoas transgênero / La ética de la atención de enfermería a las personas transgénero

ABSTRACT Objectives: to discuss ethical aspects in nursing care for transgender people. Methods: reflective study based on the dilemmas that emerges in nursing care for transgender people. The report was structured around the four bioethical principles. Results: health care for trans people is complex, transversal to many devices and specialties and longitudinal in time, that is why it requires coordinated action. There is an ethical framework in which the nursing care must be observed in the care of this group. Final Considerations: the nurse as a health worker can assume several general lines in the care of transgender patients. So, complementary training should be provided not only to professionals, but also to students of nursing and other health sciences.

RESUMO Objetivos: discutir aspectos éticos na assistência de enfermagem às pessoas transgênero. Métodos: estudo reflexivo a partir dos dilemas que surgem no cuidado de enfermagem às pessoas transgênero. O relato foi estruturado em torno dos quatro princípios bioéticos. Resultados: a atenção à saúde de pessoas trans é complexa, transversal a muitos dispositivos e especialidades e longitudinal no tempo, por isso requer ação coordenada. Existe um referencial ético no qual se enquadram os cuidados de enfermagem que devem ser observados no atendimento a esse grupo. Considerações Finais: o enfermeiro como agente de saúde pode assumir diversas linhas gerais no atendimento a pacientes transgênero. Para tal, deve ser proporcionada formação complementar não só aos profissionais, mas também aos estudantes de enfermagem e outras ciências da saúde.

RESUMEN Objetivos: debatir sobre aspectos éticos en la atención de enfermería a personas transgénero. Métodos: estudio reflexivo fundamentado sobre los dilemas que se plantean en los cuidados de enfermería a personas transgénero. El relato se ha estructurado en torno a los cuatro principios bioéticos. Resultados: la atención sanitaria a las personas trans es compleja, transversal a muchos dispositivos y especialidades y longitudinal en el tiempo por lo que precisa de la actuación coordinada. Existe un marco ético en el que se encuadran los cuidados de enfermería que se precisan en la atención a este colectivo. Consideraciones Finales: la enfermera como agente de salud puede asumir diversas líneas generales en la atención a pacientes transgénero. Para ello, se debe brindar formación adicional no solo a los profesionales, también a los estudiantes de enfermería y de las demás ciencias de la salud.