bluuebunny/crossref_metadata_2025 huggingface dataset:
miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow–derived neural crest cells
Authors: Cong Meng , Hu Jing-Jing , Yu Yan , Li Xiao-Li , Sun Xiao-Ting , Wang Li-Ting , Wu Xia , Zhu Ling-Jie , Yang Xiao-Jia , He Qian-Ru , Ding Fei , Shi Hai-Yan
Published: December 2023

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-12-10T152134Z/r/image-tiff

Our previous study found that rat bone marrow–derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.
In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke
Authors: Yuan Meng , Tang Yao , Huang Tianwen , Ke Lining , Huang En
Published: December 2023

JOURNAL/nrgr/04.03/01300535-202410000-00025/figure1/v/2024-02-06T055622Z/r/image-tiff

In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1 (PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.eB-GFAP-shPTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-shPTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.
Microglial NLRP3 inflammasome-mediated neuroinflammation and therapeutic strategies in depression
Authors: Han Qiuqin , Li Wenhui , Chen Peiqing , Wang Lijuan , Bao Xiwen , Huang Renyan , Liu Guobin , Chen Xiaorong
Published: December 2023

Previous studies have demonstrated a bidirectional relationship between inflammation and depression. Activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes is closely related to the pathogenesis of various neurological diseases. In patients with major depressive disorder, NLRP3 inflammasome levels are significantly elevated. Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic strategies. In this review, we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 inflammasome. Moreover, we outlined various therapeutic strategies that target the NLRP3 inflammasome, including NLRP3 inflammatory pathway inhibitors, natural compounds, and other therapeutic compounds that have been shown to be effective in treating depression. Additionally, we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to depression. Currently, there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression treatment. The modulation of NLRP3 inflammasomes in microglia holds promise for the management of depression. Further investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.
Cell reprogramming therapy for Parkinson’s disease
Authors: Dong Wenjing , Liu Shuyi , Li Shangang , Wang Zhengbo
Published: December 2023

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease. The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease, which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice. However, ethical issues and tumor formation were limitations of its clinical application. Induced pluripotent stem cells can be acquired without sacrificing human embryos, which eliminates the huge ethical barriers of human stem cell therapy. Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons, without the need for intermediate proliferation states, thus avoiding issues of immune rejection and tumor formation. Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease. However, there are also ethical concerns and the risk of tumor formation that need to be addressed. This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease, focusing on the use of induced pluripotent stem cells in cell replacement therapy, including preclinical animal models and progress in clinical research. The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease, as well as the controversy surrounding in vivo reprogramming. These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.
Cav3.2 channel regulates cerebral ischemia/reperfusion injury: a promising target for intervention
Authors: Dai Feibiao , Hu Chengyun , Li Xue , Zhang Zhetao , Wang Hongtao , Zhou Wanjun , Wang Jiawu , Geng Qingtian , Dong Yongfei , Tang Chaoliang
Published: December 2023

JOURNAL/nrgr/04.03/01300535-202411000-00028/figure1/v/2024-04-10T160327Z/r/image-tiff

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury. Various calcium channels are involved in cerebral ischemia/reperfusion injury. Cav3.2 channel is a main subtype of T-type calcium channels. T-type calcium channel blockers, such as pimozide and mibefradil, have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury. However, the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear. Here, in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons. The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons. We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury. Cav3.2 knockout markedly reduced infarct volume and brain water content, and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury. Additionally, Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress, inflammatory response, and neuronal apoptosis. In the hippocampus of Cav3.2-knockout mice, calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury. These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling. Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.
Therapeutic advances in neural regeneration for Huntington's disease
Authors: D'Egidio Francesco , Castelli Vanessa , Lombardozzi Giorgia , Ammannito Fabrizio , Cimini Annamaria , d'Angelo Michele
Published: December 2023

Huntington's disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington's disease. From a clinical point of view, Huntington's disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington's disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington's disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington's disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington's disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, numerous have been the attempts in several preclinical models of Huntington's disease to evaluate the feasibility of invasive and non-invasive approaches. Thus, the aim of this review is to offer an overview of the most appealing approaches spanning from stem cell-based cell therapy to extracellular vesicles such as exosomes in light of promoting neurogenesis, discussing the results obtained so far, their limits and the future perspectives regarding the neural regeneration in the context of Huntington's disease.
Interplay between the glymphatic system and neurotoxic proteins in Parkinson's disease and related disorders: current knowledge and future directions
Authors: Yue Yumei , Zhang Xiaodan , Lv Wen , Lai Hsin-Yi , Shen Ting
Published: December 2023

Parkinson's disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins, including α-synuclein, amyloid-β, and tau, in addition to the impaired elimination of these neurotoxic protein. Atypical parkinsonism, which has the same clinical presentation and neuropathology as Parkinson's disease, expands the disease landscape within the continuum of Parkinson's disease and related disorders. The glymphatic system is a waste clearance system in the brain, which is responsible for eliminating the neurotoxic proteins from the interstitial fluid. Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease, as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage. Therefore, impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration. Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson's disease and related disorders; however, many unanswered questions remain. This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson's disease and related disorders. The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins, including loss of polarization of aquaporin-4 in astrocytic endfeet, sleep and circadian rhythms, neuroinflammation, astrogliosis, and gliosis. This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson's disease and related disorders, and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.
NADPH oxidase 4 (NOX4) as a biomarker and therapeutic target in neurodegenerative diseases
Authors: Boonpraman Napissara , Yi Sun Shin
Published: December 2023

Diseases like Alzheimer's and Parkinson's diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer's disease and Parkinson's disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.
How do neurons age? A focused review on the aging of the microtubular cytoskeleton
Authors: Richardson Brad , Goedert Thomas , Quraishe Shmma , Deinhardt Katrin , Mudher Amritpal
Published: December 2023

Aging is the leading risk factor for Alzheimer's disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer's disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer's disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clear disparities between model organisms and brain regions that are worthy of further investigation. Additionally, longitudinal studies of neuronal/cytoskeletal aging should also investigate whether these age-related changes contribute not just to vulnerability to disease but also to the decline in nervous system function and behavioral output that all organisms experience. This will highlight the utility, if any, of cytoskeletal fortification for the promotion of healthy neuronal aging and potential protection against age-related neurodegenerative disease. This review seeks to summarize what is currently known about the physiological aging of the neuron and microtubular cytoskeleton in the hope of uncovering mechanisms underpinning age-related risk to disease.
Rebuilding insight into the pathophysiology of Alzheimer's disease through new blood-brain barrier models
Authors: Matsuo Kinya , Nshihara Hideaki
Published: December 2023

The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system. Blood-brain barrier breakdown is a common pathology in various neurological diseases, such as Alzheimer's disease, stroke, multiple sclerosis, and Parkinson's disease. Traditionally, it has been considered a consequence of neuroinflammation or neurodegeneration, but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal loss. Thus, the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics. To elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases, there is a growing demand for experimental models of human origin that allow for functional assessments. Recently, several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been proposed. Especially in the Alzheimer's disease field, the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain barrier. In this review, we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer's disease from pathological analyses, imaging studies, animal models, and stem cell sources. Additionally, we discuss the potential future directions for blood-brain barrier research.
Elucidation of Immune Regulation Mechanism of Renshen Guben Oral Liquid by Network Pharmacology and Molecular Docking
Authors: Tan Ying-Ying , Liu Ying-Ying , Zhang Jing-Yuan , Li Jia-Lin , Ye Pei-Zhi , Stalin Antony , Fan Xiao-Tian , Huang Zhi-Hong , Li Bing , Wu Chao , Lu Shan , Wu Zhi-Shan , Zhang Xiao-Meng , Cheng Guo-Liang , Wu Jia-Rui , Mou Yan-Fang
Published: December 2023

Objective:

To investigate the mechanism of Renshen Guben oral liquid (RSGB) enhancing immune function.

Materials and Methods:

Network pharmacology and molecular docking were used to intuitively demonstrate the mechanism of immune regulation of RSGB.

Results:

A total of 112 active compounds of RSGB were found, and 501 targets were predicted. Furthermore, 2974 immune targets were obtained from UniProt and NCBI Gene databases, and 111 common targets of RSGB and immunity were obtained. Among them, interleukin (IL) 6, tumor necrosis factor, AKT1, VEGFA, STAT3, MAPK1, SRC, EGFR, IL1B, and PTGS2 might be the key targets for RSGB to improve immunity. ClueGO and Kyoto Encyclopedia of Genes and Genomes analysis showed that the immunoregulatory mechanism of RSGB may find a relation with the B cell receptor signaling pathway and T cell receptor signaling pathway. Furthermore, this study preliminarily explored the mechanism of RSGB improving menopausal syndrome, polycystic ovary syndrome, and cancer-related fatigue by enhancing immunity.

Conclusions:

RSGB can improve the body’s immunity through multicomponent, multitarget, and multipathway. In addition, RSGB can also improve the immune capacity of the body to assist in the treatment of diseases, which has great potential as an immunomodulator.
Efficacy of Hypnotherapy in the Management of Fibromyalgia: A Prospective Randomized Controlled Study
Authors: Baykuş Hürmet Ebru , Güç Ayşe Atilabey , Karabaş Çağlar , Çalış Havva Talay
Published: December 2023

Objective:

A multi-modal approach to fibromyalgia syndrome is necessary as it is affected by emotional, cognitive, and behavioral factors. In this context, hypnosis is one of the treatment methods used in fibromyalgia. However, studies on the use of hypnosis in fibromyalgia have mostly been conducted with short treatment durations of self-hypnosis. For this reason, we aimed to conduct this study in which the hypnosis sessions were face-to-face and the treatment duration was longer.

Materials and Methods:

Twenty-five patients who met the fibromyalgia diagnostic criteria published in the American College of Rheumatology (ACR) 2016 and whose medical treatment was planned were included in the study. A total of 20 patients completed the study (10 hypnosis group and 10 control group). No additional treatment was applied to the control group other than medical treatment and exercise recommendations. In addition to medical treatment and exercise, patients in the hypnosis group received face-to-face hypnosis therapy once a week for 60 min, a total of 10 sessions. Evaluations of the patients before the treatment and in the 3rd month after the treatment were made with the pain score and the fibromyalgia disease activity score.

Results:

Ages 18–65 years, with widespread pain for at least 3 months, according to ACR 2016 fibromyalgia diagnostic criteria; A total of 20 patients with fibromyalgia, 10 in the hypnosis treatment group and 10 in the control treatment group completed the study. When the 3rd month Visual Analog Scale (VAS) and Fibromyalgia Impact Questionnaire (FIQ) values of the group receiving hypnosis treatment were compared with the control group, a statistical difference was found (P < 0.001). When the pre-treatment VAS and FIQ values of the group receiving hypnosis treatment were compared with the 3rd month values, a statistically significant improvement was found (respectively; P = 0.006, P = 0.005). When the pretreatment and 3rd month VAS and FIQ values of the control group were compared, no statistical difference was found (P = 0.063).

Conclusions:

Hypnosis treatment is effective in reducing pain and increasing daily life activities in fibromyalgia patients, and no side effects were reported. It can be considered a complementary treatment within the multimodal approach in fibromyalgia patients.
Close Correlations Between Carotid Arterial Mean Blood Flow Velocity, Body Mass Index, and Temperature in Normal Individuals
Authors: Zhu Xiang , Gao Wei , Chi Yong , Wang Zhi-Yong , Shao Jun-Jie
Published: December 2023

Objective:

Assessing carotid and radial pulses is an essential sphygmology method in traditional Chinese medicine (TCM). It is believed in TCM and by doctors that pulse force is markedly linked with the physiological state of a human, including body mass index (BMI) and temperature. However, comprehensive analysis elucidating these potential correlations remains undetermined. Therefore, this investigation aimed to assess the association of pulse strength with human metabolism.

Materials and Methods:

The mean blood flow velocity (MBFV) of the carotid artery and pulse force of 122 healthy adults included in this investigation were assessed using ultrasound and manual palpation. Their thermal texture map was also acquired.

Results:

No substantial variation was observed in the carotid arterial MBFV among normal individuals (P > 0.05) regardless of body side and gender. However, young individuals had higher blood velocity than middle-aged individuals (P < 0.05). Furthermore, it was identified that MBFV was negatively associated with BMI and torso temperature; however, it was positively linked with hand temperature.

Conclusions:

This investigation revealed that carotid arterial MBFV could indicate the physical state of humans, including BMI and temperature, and therefore, is valuable for elucidating the effect of TCM on yin–yang. The data validated some TCM beliefs and supported the implementation of sphygmology in TCM.
Five Cases of Idiopathic Sciatic Mononeuropathy: Clinical, Electrophysiological, Radiological, and Histological Features
Authors: Khadilkar Satish , Kamat Saurabh , Deshmukh Narayan , Shah Neha , Shetty Vanaja , Shah Swati , Halani Hiral A. , Mansukhani Khushnuma
Published: December 2023

Background:

Common etiologies of sciatic mononeuropathy are compressive, infiltrative, traumatic, or diabetic. However, in a proportion of patients, the etiology remains elusive despite extensive serological, electrophysiological, radiological, and histological investigations.

Methods:

Patients with unexplained sciatic mononeuropathy were studied with regard to their clinical, radiological, pathological, and treatment aspects.

Results:

We could identify five cases of sciatic mononeuropathy wherein the etiology remained unknown even after a comprehensive evaluation. The compressive, metabolic, hematological, and immune causes were ruled out with necessary investigations. The clinical, electrophysiological, radiological, and histological features of these patients are discussed.

Conclusion:

The etiology of sciatic mononeuropathy can remain obscure in certain instances in spite of the comprehensive workup. The role of investigations and the exclusion process of various diagnostic entities are discussed.
Causes and pathological characteristics of native renal thrombotic microangiopathy in an Egyptian population with clinical correlation
Authors: Hamza Wael M , Shaker Amr M
Published: December 2023

Introduction

Thrombotic microangiopathy (TMA) in needle renal biopsy stands as one of the most important diagnostic critical values in nephropathology, and a diagnostic challenge in many of affected patients. The condition has various etiologies with different underlying pathogenetic mechanisms. The urgent handling of such cases with clinical anticipation and histopathological diagnosis draws the management and prognosis of these patients.

Objectives

In this paper, the histopathological characteristics of native renal TMA lesions were analyzed with determination of the possible underlying etiology and correlation with the clinical findings in Egyptian patients over a duration of 5 years.

Patients and methods

A retrospective study was conducted to analyze the pathological findings and clinical data of our patients with biopsy-proven renal TMA over a duration of 5 years (from January 2014 to January 2019). One hundred and twenty-seven cases were included.

Results

The prevalence of native renal TMA in our patients was 3.90% with male: female ratio (0.9: 1) and age range (2–80 years). The most common manifestation was acute kidney injury (64.57%). An underlying etiology was identified in 88 (69.29%) cases and the most common cause was association with autoimmune diseases (27.27%), followed by drug-induced TMA (15.91%), infection-associated TMA, and malignant hypertension (14.77% each). Acute TMA pathological features without evidence of chronicity were seen in 56 (44.09%) cases. The most encountered acute glomerular pathological lesion was irregular capillary wall thickening (68.50%), followed by tuft thrombosis (67.72%) and endothelial swelling (63.78%). Cortical necrosis was detected in 14 (11.02%) patients. The highest percentage of chronic damage features was detected in malignant hypertension and pregnancy-associated TMA.

Conclusion

TMA is a rare finding in needle native renal biopsy in the study’s Egyptian population with varied underlying etiological agents. The clinicopathological integration and implementing the recent clinical laboratory tests for identification of the underlying etiology of TMA has utmost importance to guide the appropriate management plan of these patients.
Evaluating the expression of immunohistochemical panel of p53, CDX2, IMP3 and AMCAR in grading dysplasia of Barrett’s esophagus and predicting the progression to esophageal adenocarcinoma
Authors: Bassyoni Omneya Y , Abdalla Rana M , Eleleimy Hiam A
Published: December 2023

Objective

Barrett’s esophagus (BE) is an established precursor to esophageal adenocarcinoma, which has a poor prognosis unless detected at an early stage. The progression of BE to adenocarcinoma is slow and unpredictable. Currently, the best predictor of adenocarcinoma is histological detection of dysplasia.

Accurate grading of dysplasia and especially discriminating low-grade dysplasia LGD from high-grade dysplasia HGD is important for management. Marked variability exists when diagnosing dysplasia in BE. This highlights the need for a diagnostic adjunct, especially in histologically challenging cases.

This study aims at evaluating the role of immunohistochemical expression of (p53, IMP3, AMCAR and CDx2) in Barrett’s oesophagus spectrum, to increase the diagnostic accuracy of grading dysplasia and predicting progression risk.

Methods

This is a retrospective immunohistochemical study, performed on selected 52 cases of esophageal biopsies.

Results

The p53 was negative in nondysplastic Barrett’s esophagus (ND-BE) and LGD and strong positivity towards HGD/esophageal adenocarcinoma (EAC). CDX2 showed highest expression among ND-BE and decreased towards EAD. IMP3 and AMCAR were negative in all cases of ND-BE with gradual increase among HGD/esophageal adenocarcinoma cases.

IMP3, AMCAR, and CDX2 were found to be more sensitive in detecting HGD (80%, 70% & 70%). Meanwhile, p53 is more specific (100%), IMP3 and AMCAR are more sensitive discriminating LGD from HGD (80%) than p53 and CDX2 (60%, 70%).

Conclusion

This combined panel of p53, CDX2, IMP3, and AMACR could be used in conjunction with histology as a promising tool to accurately predict progression form BE to HGD/adenocarcinoma with a great value for early detecting high grade dysplasia, discriminating it from LGD, improving risk stratification in BE, and optimizing patient care.
Expression status of MLH1 and MSH2 mismatch repair proteins in colorectal carcinoma
Authors: Mohamed Said A-A , Tealeb Al-Sayed MI , Abd-Elhameed Nageh R , Eldowik Yasser M
Published: December 2023

Background

Colorectal carcinoma (CRC) is a main cause of morbidity and mortality worldwide. Lynch syndrome or hereditary nonpolyposis colorectal carcinoma is a cancer syndrome that accounts for 5–10% of cases of CRCs, and it is caused by a germline mutation in one or more of mismatch repair (MMR) genes, that is, MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6, PMS1 homolog (PMS2), and epithelial cellular adhesion molecule. Nearly 90% of cases have mutations in either MLH1 or MSH2 gene.

Aim

To study the immunohistochemistry of MLH1 and MSH2 MMR proteins in CRC and to study the association of abnormal MMR protein expression with clinicopathological parameters.

Patients and methods

This study included 48 cases of consecutive colectomy specimens submitted to the Pathology Department of Al-Azhar University hospitals and some private laboratories. The patients’ age ranged between 22 and 81 years (median, 53 years), and 35 (72.9%) cases were male and 13 (27.1%) cases were females.

Results

Among the 48 studied CRC cases, 11 (22.9%) cases were MMR deficient, whereas 37 (77.1%) cases were MMR proficient. MMR defects owing to germline mutations of MSH2 were eight (72.7%) cases of the MMR deficient and that due to the functional missense mutation or hypermethylation of MLH1 were three (27.3%) cases.

Conclusions

Immunohistochemistry for MLH1 and MSH2 is a rapid, reliable, effective, and relatively inexpensive method to detect MMR deficiency in CRC tumors. The patterns of expression of MMR protein demonstrated distinct associations with right-sided mucinous colon carcinoma and high tumor grade, which may be valuable for prognosis and clinical treatment of CRCs.
Preferential expression of prostate specific membrane in CD34 labeled Neo-vasculature of Hepatocellular carcinoma: Prognostic and therapeutic potentials
Authors: Abd El Khalek Safaa MM , Mohammed Mona QR , Al Balakosy Amira M
Published: December 2023

Background

Hepatocellular carcinoma (HCC) is highly prevalent and lethal worldwide. Viral hepatitis related HCC represents 80% of all HCC cases. Eventually, angiogenesis becomes a crucial step in all HCCs. Angiogenetic markers are shared by non-malignant conditions. Finding a marker specifically expressed in tumor-vasculature and predict prognosis can provide optimal guide for decision making and involvement of new therapeutic options. prostate specific membrane antigen (PSMA) is a type II transmembrane protein upgraded in many tumours with promising role in prostate cancer as a potential prognostic and therapeutic indicator. However, the role of PSMA in HCC is not widely studied yet. This work aimed at evaluating PSMA expression in HCC.

Methodology

PSMA immunohistochemical staining was performed on 73 HCC cases to evaluate its expression. Relationship to different clinico-pathologic parameters was assessed statistically.

Results

PSMA was expressed in tumor-vasculature of HCC with 32% showed high expression. Adjacent non-tumoral tissue showed negative expression for PSMA. PSMA expression was significantly correlated with viral hepatitis related HCC (P=0.03), tumor grade (P=0.07), stage, node and distant metastasis (P=0.001 each). PSMA is the most independent predictor for OS and PFS.

Conclusion

PSMA is expressed preferentially in tumor-vasculature of HCC with higher expression in viral hepatitis related HCC and correlation with poor prognostic parameters, short OS and PFS. PSMA is considered a promising prognostic and therapeutic marker in HCC especially viral hepatitis related.
Immunohistochemical expression of CXCL5 as a valuable prognostic marker in urinary bladder urothelial carcinoma
Authors: Ahmed Nagwa Abd El-Sadek , Abdelnaby Amira A , Elsherief Ahmed MMA , Abdelghaffar Alshaymaa , Abdelkareem Rasha M
Published: December 2023

Background and aim

Urothelial carcinoma (UC) is the most common histologic subtype of bladder carcinoma. Detection of novel biomarkers that could predict UC progression and prognosis represents an active focus of research in the oncology field. CXCL5 is a member of the CXC chemokine family. It has been implicated in progression of many cancers, but its prognostic value in UC remains unclear. This study aimed to evaluate the immunohistochemical expression of CXCL5 in noninvasive and invasive UC of the urinary bladder and to correlate its expression with different studied clinicopathological characteristics to evaluate its potential prognostic value.

Patients and methods

A total of 60 specimens of primary invasive and noninvasive urothelial bladder carcinomas were included in this study. Paraffin-embedded tissue blocks were prepared from the specimens. Two serial tissue sections were obtained from each specimen. One tissue section was stained by hematoxylin and eosin stain and examined to confirm diagnosis, histologic subtype, tumor grade, muscle invasion, and presence or absence of bilharzial infestation, and the second tissue section was subjected to immunohistochemical using anti-human CXCL5 antibody.

Results

Studying the association between CXCL5 expression and different clinicopathologic parameters in urothelial bladder carcinoma revealed a statistically significant correlation between its expression and poor prognostic indicators. CXCL5 expression is significantly correlated with poorly differentiated (P=0.025), advanced stage (P=0.039), and invasive tumors (P=0.002).

Conclusion

The current study revealed that CXCL5 overexpression in urothelial bladder carcinoma is strongly associated with adverse prognostic factors. CXCL5 might be considered as a reliable biomarker in predicting tumor progression and poor prognosis.
FOXM1 and MMR genes immunohistochemical expression in colorectal cancer: promising prognostic insights and candidate therapeutic targets
Authors: Shash Lobna S , Elgohary Shimaa A , Ibrahim Riham A
Published: December 2023

Background and objectives

Colorectal cancer (CRC) high mortality in developing countries necessitates the delineation of the underlying mechanisms compromising its prognosis despite of current advances. Mismatch repair (MMR) genes protein expression is established as a surrogate to categorize CRC MMR status with different prognostic and therapeutic considerations, variations are observed not only among different classes but also within the same class. FOXM1 is involved in multitask carcinogenesis and is recently targeted in some cancers. Our objective was to study FOXM1 expression in different CRC subclasses to exploit any potential inferences of its role.

Material and methods

This retrospective study encompassed 51 CRC specimens received in Ain Shams University Hospital, immunohistochemical studies for microsatellite stability genes to determine MMR status and FOXM1 expression were performed. Results were statistically compared and correlated to the clinicopathological prognostic indices.

Results

FOXM1 expression was statistically significant when correlated to lymphovascular invasion and nodal metastasis. Despite failing to establish a statistical correlation with FOXM1 expression level yet a suggestive tendency of overexpression with precursor tubulovillous adenoma, mucinous and signet ring CRC, grade 3, PT3 was noted. FOXM1 high expression concorded with MMR deficient status, mounting to a statistical significance in right CRCs, this association was disrupted when nodal status was tested.

Conclusion

FOXM1 shows varying expression in CRC subclasses, variations did not follow a consistent synergistic pattern thus the effect of FOXM1 on prognostic indicators likely involves molecular coded cross-talks with mismatch repair genes as well as others. We offer innovative insights for prognostic aptitudes of FOXM1 that might pave promising utility in future if further validated.
Comparison of sedation efficacy of intravenous infusion of dexmedetomidine versus propofol in terms of opioid consumption in patients requiring postoperative mechanical ventilation after head and neck onco-surgeries – A randomized prospective study
Authors: Patel Anuradha , Garg Rakesh , Bharti Sachidanand Jee , Kumar Vinod , Gupta Nishkarsh , Mishra Seema , Bhatnagar Sushma , Kumar Abhishek
Published: December 2023

Background:

The conventional drug regimen of sedation for patients requiring mechanical ventilation in an intensive care unit (ICU) is propofol or midazolam. Dexmedetomidine is a newer drug for sedation with a better clinical profile. We conducted this study to compare the sedative efficacy of dexmedetomidine versus propofol in patients after head and neck cancer surgeries requiring mechanical ventilation.

Methods:

After ethics committee approval and written informed consent, 80 patients undergoing head and neck onco-surgery were recruited. The patients were randomly allocated to group I [1 mg/kg of bolus propofol over 15 minutes followed by infusion of 1 mg/kg/hour titrated by increasing or decreasing the infusion dose to Ramsay Sedation Score (RSS) 2–4] or group II (a loading dose of dexmedetomidine 1 mcg/kg over 15 minutes followed by a maintenance dose of 0.4 µg/kg/hour titrated to desired sedation level). The RSS, behavioral pain scale (BPS), heart rate, blood pressure, fentanyl consumption, additional sedative agent, extubation time, length of ICU stays, mechanical ventilation duration, side effects, and patient’s satisfaction were noted.

Results:

Total fentanyl required was 0.56 ± 0.13 µg/kg/hour in group II and 0.58 ± 0.18 µg/kg/hour in group I (P = 0.75). Extubation time, RSS, BPS, patient satisfaction, and ICU duration were similar in both the groups. The incidence of hemodynamic-related adverse effects were 41.67% in group II and 11.11% in group I (P = 0.006).

Conclusion:

The fentanyl requirement was comparable in both the groups in the postoperative period. Dexmedetomidine was associated with an increased incidence of bradycardia and hypotension as compared to the propofol group. Propofol should be the preferred sedative for postoperative mechanical ventilation after head and neck onco-surgeries.
Effects of electrode placement on symptoms, memory, and sustainment of results after electroconvulsive therapy- A comparative study
Authors: Chaudhary Ankit , Maggu Gaurav , Chaudhury Suprakash , Saldanha Daniel
Published: December 2023

Background:

The memory-related side-effects rank among the strongest reasons for hostility against Modified Electroconvulsive Therapy (MECT). Most of the studies comparing the Unilateral v/s Bilateral Electrode placements on memory have been conducted on patients with depression while very few studies have been conducted on patients with psychosis in the Indian population.

Aim:

To compare the effects of right unilateral (RU/L) and bilateral (B/L) MECT on the severity of symptoms as well as memory in patients with psychosis after the fourth session and two weeks after the final session of the MECT.

Materials and Methods:

One hundred patients having a psychotic illness were randomized into either RU/L or B/L group. Comprehensive psychopathological rating scale (CPRS), clinical global impressions scale (CGI-S), and PGI-memory scale were applied before starting of MECT, after four sessions of MECT and two weeks after the last session of ECT.

Results:

The results show similar symptomatic improvement in patients receiving RU/L and B/L MECT and the results persisted beyond the therapy sessions. But, in the case of RU/L-MECT group, the deterioration in memory was less as compared to the B/L-MECT group. Both groups had no significant difference in psychopathology and its severity (CPRS and CGI). Both groups were significantly different in memory side effects after the fourth session and two weeks after the last session. Both groups showed a consistent downward trend in psychopathology and its severity. The consistent fall in the total PGI scores remained even after two weeks of the final session in the B/L group (total of six points as compared to baseline) while it came to baseline levels in the RU/L group. Both groups differed significantly in total PGI scores after the fourth session and two weeks after the final session.

Conclusion:

This study points toward a favorable outcome in the case of therapeutic response with MECT without any significant difference between both types of electrode placements and even after stopping MECT, the improvement appears to be stable over time. Although, there was a side-effect of memory impairment, it appears to be for a shorter duration and it improves with time. The side-effect profile of RU/L electrode placement is lower as compared to bilateral placement. In the post-MECT period, the patients receiving MECT with RU/L electrode placement showed better improvement in memory functions.
Parity of esteem: A global COVID-19 vaccination approach for people with mental illnesses, based on facts from 34 countries; recommendations and solutions
Authors: Shoib Sheikh , Saeed Fahimeh , Philip Sharad , Chandradasa Miyuru , Das Soumitra , de Filippis Renato , Yousaf Zohaib , Ojeahere Margaret , Gad Hasnaa K. , Yadivel Ramyadarshni , Legris Zahra , Jatchavala Chonnakarn , Paul Ravi , Gupta Anoop K. , Handuleh Jibril I. M. , Gürcan Ahmet , da Costa Mariana Pinto , Dannatt Lisa , Ahmad Araz R. , Jaguga Florence , Saleem Sheikh M. , Sawitri Brihastami , Arif Nigar , Islam Md. Saiful , Haque Md Ariful , Őri Dorottya , Chumakov Egor , Swed Sarya , Roza Thiago H. , Islam Sheikh Mohammed Shariful
Published: December 2023

Background:

The coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has detrimental effects on physical and mental health. Patients with severe mental illness are at higher risk of contracting the virus due to social determinants of health. Vulnerable populations include the elderly, people with pre-existing conditions, and those exposed to SARS-CoV-2. Unfortunately, only a few countries have updated vaccination strategies to prioritize patients with mental illnesses. Therefore, we aimed to explore whether individuals with mental disorders are prioritized in vaccine allocation strategies in different world regions. They are often neglected in policymaking but are highly vulnerable to the threatening complications of COVID-19.

Methods:

A questionnaire was developed to record details regarding COVID-19 vaccination and prioritizations for groups of persons with non-communicable diseases (NCDs), mental disorders, and substance use disorders (SUDs). NCDs were defined according to the WHO as chronic diseases that are the result of a combination of genetic, physiological, environmental, and behavioral factors such as cardiovascular diseases, cancer, respiratory diseases, and diabetes.

Results:

Most countries surveyed (80%) reported healthcare delivery via a nationalized health service. It was found that 82% of the countries had set up advisory groups, but only 26% included a mental health professional. Most frequently, malignancy (68%) was prioritized followed by diabetes type 2 (62%) and type 1 (59%). Only nine countries (26%) prioritized mental health conditions.

Conclusion:

The spread of the coronavirus has exposed both the strengths and flaws of our healthcare systems. The most vulnerable groups suffered the most and were hit first and faced most challenges. These findings raise awareness that patients with mental illnesses have been overlooked in immunization campaigns. The range of their mortality, morbidity, and quality of life could have widened due to this delay.