bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferroptosis and endoplasmic reticulum stress in ischemic stroke
Authors: Li Yina , Li Mingyang , Feng Shi , Xu Qingxue , Zhang Xu , Xiong Xiaoxing , Gu Lijuan 
Published: August 2023

Abstract
Ferroptosis is a form of non-apoptotic programmed cell death, and its mechanisms mainly involve the accumulation of lipid peroxides, imbalance in the amino acid antioxidant system, and disordered iron metabolism. The primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum, and the progression of inflammatory diseases can trigger endoplasmic reticulum stress. Evidence has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell survival. Ferroptosis and endoplasmic reticulum stress may occur after ischemic stroke. However, there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic stroke. This review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke, aiming to provide a reference for developing treatments for ischemic stroke.
Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina
Authors: Norte-Muñoz María , García-Bernal David , García-Ayuso Diego , Vidal-Sanz Manuel , Agudo-Barriuso Marta 
Published: August 2023

Abstract
Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models. Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration, namely trophic factor deprivation and neuroinflammation. Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement. However, little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system. Here, we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system, focusing on recent work in the retina and the importance of the type of transplantation.
Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases
Authors: Gonzalez-Cano Sonia Irais , Flores Gonzalo , Guevara Jorge , Morales-Medina Julio Cesar , Treviño Samuel , Diaz Alfonso 
Published: August 2023

Abstract
Aging is a natural phenomenon characterized by a progressive decline in physiological integrity, leading to a deterioration of cognitive function and increasing the risk of suffering from chronic-degenerative diseases, including cardiovascular diseases, osteoporosis, cancer, diabetes, and neurodegeneration. Aging is considered the major risk factor for Parkinson’s and Alzheimer’s disease develops. Likewise, diabetes and insulin resistance constitute additional risk factors for developing neurodegenerative disorders. Currently, no treatment can effectively reverse these neurodegenerative pathologies. However, some antidiabetic drugs have opened the possibility of being used against neurodegenerative processes. In the previous framework, Vanadium species have demonstrated a notable antidiabetic effect. Our research group evaluated polyoxidovanadates such as decavanadate and metforminium-decavanadate with preventive and corrective activity on neurodegeneration in brain-specific areas from rats with metabolic syndrome. The results suggest that these polyoxidovanadates induce neuronal and cognitive restoration mechanisms. This review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the brain, constituting a therapeutic alternative for aging and neurodegenerative diseases.
Annexin A1 in the nervous and ocular systems
Authors: Wang Aijia , Zhang Hong , Li Xing , Zhao Yin 
Published: August 2023

Abstract
The therapeutic potential of Annexin A1, an important member of the Annexin superfamily, has become evident in results of experiments with multiple human systems and animal models. The anti-inflammatory and pro-resolving effects of Annexin A1 are characteristic of pathologies involving the nervous system. In this review, we initially describe the expression sites of Annexin A1, then outline the mechanisms by which Annexin A1 maintains the neurological homeostasis through either formyl peptide receptor 2 or other molecular approaches; and, finally, we discuss the neuroregenerative potential qualities of Annexin A1. The eye and the nervous system are anatomically and functionally connected, but the association between visual system pathogenesis, especially in the retina, and Annexin A1 alterations has not been well summarized. Therefore, we explain the beneficial effects of Annexin A1 for ocular diseases, especially for retinal diseases and glaucoma on the basis of published findings, and we explore present and future delivery strategies for Annexin A1 to the retina.
Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice
Authors: Mu Jiao , Hao Liufang , Wang Zijue , Fu Xuyang , Li Yusen , Hao Fei , Duan Hongmei , Yang Zhaoyang , Li Xiaoguang 
Published: August 2023

Abstract

JOURNAL/nrgr/04.03/01300535-202403000-00039/inline-graphic1/v/2023-09-27T141015Z/r/image-tiff

Stroke can cause Wallerian degeneration in regions outside of the brain, particularly in the corticospinal tract. To investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke, we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal tract. We first used a routine, sensitive marker of axonal injury, amyloid precursor protein, to examine Wallerian degeneration of the corticospinal tract. An antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex, with no positive signal in distal parts of the corticospinal tract, at all time points. To improve visualization of Wallerian degeneration, we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing axons. Using this approach, we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after stroke. In addition, microglia mobilized and activated early, from day 7 after stroke, but did not maintain a phagocytic state over time. Meanwhile, astrocytes showed relatively delayed mobilization and a moderate response to Wallerian degeneration. Moreover, no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal tract. In conclusion, our data provide evidence for dynamic, pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.
Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis
Authors: Tang Xiuling , Yan Tao , Wang Saiying , Liu Qingqing , Yang Qi , Zhang Yongqiang , Li Yujiao , Wu Yumei , Liu Shuibing , Ma Yulong , Yang Le 
Published: August 2023

Abstract

JOURNAL/nrgr/04.03/01300535-202403000-00040/inline-graphic1/v/2023-09-27T141015Z/r/image-tiff

β-Sitosterol is a type of phytosterol that occurs naturally in plants. Previous studies have shown that it has anti-oxidant, anti-hyperlipidemic, anti-inflammatory, immunomodulatory, and anti-tumor effects, but it is unknown whether β-sitosterol treatment reduces the effects of ischemic stroke. Here we found that, in a mouse model of ischemic stroke induced by middle cerebral artery occlusion, β-sitosterol reduced the volume of cerebral infarction and brain edema, reduced neuronal apoptosis in brain tissue, and alleviated neurological dysfunction; moreover, β-sitosterol increased the activity of oxygen- and glucose-deprived cerebral cortex neurons and reduced apoptosis. Further investigation showed that the neuroprotective effects of β-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke. In addition, β-sitosterol showed high affinity for NPC1L1, a key transporter of cholesterol, and antagonized its activity. In conclusion, β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.
Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model
Authors: Zhang Longqing , Tan Xi , Song Fanhe , Li Danyang , Wu Jiayi , Gao Shaojie , Sun Jia , Liu Daiqiang , Zhou Yaqun , Mei Wei 
Published: August 2023

Abstract

JOURNAL/nrgr/04.03/01300535-202403000-00046/inline-graphic1/v/2023-09-27T141015Z/r/image-tiff

Activated G-protein-coupled receptor 39 (GPR39) has been shown to attenuate inflammation by interacting with sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). However, whether GPR39 attenuates neuropathic pain remains unclear. In this study, we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated rats. Intrathecal injection of TC-G 1008, a specific agonist of GPR39, significantly alleviated mechanical allodynia in the rats with spared nerve injury, improved spinal cord mitochondrial biogenesis, and alleviated neuroinflammation. These changes were abolished by GPR39 small interfering RNA (siRNA), Ex-527 (SIRT1 inhibitor), and PGC-1α siRNA. Taken together, these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1α pathway in rats with spared nerve injury.
Sexual Dysfunction in Diabetes Mellitus – An Observational Cohort Study
Authors: Mohan Gurinder , Mann Gurbir Singh , Sikri Tejinder 
Published: August 2023

Objectives: The objectives of the study are to assess the prevalence and type of sexual dysfunction (SD) in males and females living with diabetes mellitus and to further assess erectile dysfunction in males who score more than 10 points in the Arizona Sexual Experience (ASEX) scale with help of the International Index of Erectile Function-5 (IIEF-5) scale. Materials and Methods: An observational cohort study was conducted on 153 diabetic patients visiting SGRDIMSR hospital, Vallah, Sri Amritsar in the Punjab region of North India. Patients aged between 18 and 50 years who were sexually active and in a healthy sexual relationship with their partner were included in the study after an informed consent. ASEX score was used for the assessment of SD and males who score more than 10 points were further assessed for erectile dysfunction with the help of IIEF-5 scale. SPSS Statistics for Windows, Version 23.0. Armonk, NY, USA: IBM Corp., Chicago, was used for data analysis. Results: SD was prevalent in 64.05% ( n = 98) of study participants overall, 65.9% ( n = 5) in female and 61.5% ( n = 40) in male groups, respectively. Mean scores of each sexual domain were drive (3.85 ± 1.10) > overall satisfaction (3.34 ± 1.06) > orgasm (3.14 ± 0.96) > arousal (3.11 ± 0.84) > erection/lubrication (2.65 ± 0.82) in that order. 69.84% of male diabetic had some degree of erectile dysfunction as assessed further by IIEF-5 score. The prevalence of SD was found to be higher in patients belonging to elderly age group ( P = 0.001), longer duration of diabetes ( P = 0.001), and deteriorating glycemic control ( P = 0.001). Conclusion: Diabetes-related SD is quite prevalent in diabetic patients with 6 out of every 10 patients experiencing this problem. Thus, sexuality needs to be discussed frequently and openly with diabetic patients. In our study, factors such as elderly age of the patient, longer duration of diabetes, and worsening glycemic control of the patient are found to increase the prevalence of SD. Furthermore, the prevalence is higher in patients who already have existing complications of diabetes such as neuropathy, retinopathy, or albuminuria.
A study of phyllode tumors, pathological parameters, and clinical correlations
Authors: Ahmed Amal N. , Elshiekh Sara M. , El Dawi Nadia I.A. 
Published: August 2023

Objectives
Phyllode tumors (PTs) represent a unique entity as mixed fibroepithelial tumors of the breast, which are characterized by a particular histologic appearance, and biologically by frequent local recurrence and low metastatic potential. We aim to study patients with PTs to determine the different histopathological features regarding, tumor grade, margin, hemorrhage, heterologous differentiation, and clinical correlations regarding age, sex, site, local recurrence, and distant metastasis in Sudanese patients.

Materials and methods
This descriptive retrospective study was carried out on PT specimens obtained from the Pathology Department at National Health Laboratory (NHL), Soba University Hospital (SUH), and Khartoum Teaching Hospital (KTH) during the interval between January 2008 and December 2011. Clinical data were collected from patients’ request forms. The slides were reexamined by two histopathologists using WHO classification of PTs, 2012. The data were analyzed using Statistical Package for Social Sciences.

Results
The study included 59 specimens diagnosed as PTs. After reexamination of the slides, two cases were excluded, one being a spindle-cell sarcoma and another being a fibroadenoma. The age of the patients ranged from 18 to 80 years. The most common affected age group was 21–40 years. The mean age was 35±1.75 years, and all of them were females. The tumors were found to occur with an equal propensity in either breast. In total, 18 (35.3%) cases were considered histologically benign, 28 (54.9%) cases were considered malignant, and five (9.8%) cases were classified as borderline. Pushing margins were present in all the cases, except three histologically malignant cases, in which the margin was infiltrative. A statistically significant positive relationship was present between tumor grade and presence of hemorrhage (P<0.05). Tumor size was significantly related to histological grade also (P<0.04). However, an insignificant relation was present between local recurrence and tumor grade (P<0.065). Heterologous mesenchymal differentiation was present only in histologically malignant cases. Regional lymph-node involvement was not detected in any of the studied cases.

Conclusion
In our study, PTs occurred exclusively in females, commonly in the age group 21–40 years, the mean age in our study was 35 years, which is 5 years younger than the mean age reported in the literature, with no reporting of cases below 18 years. Malignant lesions outnumbered the benign lesions. Heterologous differentiation, hemorrhage, large tumor size, and infiltrating tumor margin are positively related to histologically malignant cases. Local recurrence was not significantly related to malignant phenotype, it may reflect the importance of adequate surgical margin.
Prognostic significance of expressed androgen receptor, p53, and p53 mutation in molecular subtypes of breast cancer
Authors: Huwait Hassan F. , Abdulkhaliq Altaf A. , Abd Elmoneim Hanan M. , Nafady Asmaa , Elzahrany Huda R. , Edrees Azzahra , Babtain Nada , Elgendy Hamed , Nafady-Hego Hanaa 
Published: August 2023

Background
Despite the introduction of several methods and new therapeutics to classify and treat breast cancer, it remains the most common cancer among women and contributes to higher mortality rates worldwide.

Purpose
This study aimed to analyze the expression levels of the androgen receptor (AR), P53 protein, and P53 mutations among molecular subtypes of breast cancers and their correlation with patients’ outcome.

Patients and methods
Immunostaining for estrogen receptor (ER), progesterone receptor (PR), Ki-67, and human epidermal growth factor receptor 2 (HER2) to stratify breast cancers into basal-like, HER2 type, luminal A or B types. AR, P53 expressions, and P53 mutations was compared among groups.

Results
Overall, 37.5% of basal-like and 7.1% of HER2 types of invasive breast carcinomas were AR positive. P53 was expressed in 62.5 and 50% of basal-like and HER2 types, respectively. The P53 mutation varied significantly among the molecular subtypes (P<0.0001) and was found in 43.8 and 42.9% of basal-like and HER2 types, respectively. Extensive nodal status, higher stage, and P53 mutation independently predicted the overall survival. AR-negative and P53 mutation-positive tumors had intermediate or poor Nottingham Prognostic Index and were more often nodal positive, higher grade, and higher stage than AR-positive and P53 mutation-negative tumors, respectively, and P53-expressing tumors.

Conclusion
Our findings highlight the importance of AR, P53, and P53 mutations as differentiating cofactors and suggest that the targeting of these marker pathways could lead to novel therapies for those patients with limited therapeutic options. AR could be a potential therapeutic target for the management of breast cancer.
Immunohistochemical expression of poly(ADP-ribose) polymerase 1 and androgen receptors in triple-negative breast cancer
Authors: Shabana Marwa E. , El Din Amina A. Gamal , Anis Shady , Elalfy Zahraa Sh. , Rabah Thanaa M. , Kamel Noura 
Published: August 2023

Background
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. It accounts for 15–20% of all types of breast cancer. Many research studies have begun to study the role of immunotherapy markers for possible TNBC treatment, among which are poly (ADP-ribose) polymerase 1 (PARP-1) and androgen receptors (ARs).

Aim
The aim of the study was to examine the immunohistochemical expression of each of PARP-1 and ARs in TNBC for their possible use as target therapy.

Patients and methods
A total of 52 paraffin blocks of TNBC cases were received from private laboratories with known status of detailed history. The expression of each of PARP-1 and ARs was studied by immunohistochemistry. Nuclear intensity and area percentage of the markers were evaluated using an image analysis system.

Result
PARP-1 was highly expressed in a large percentage of TNBC (91%). There was a significant relation between PARP-1 expression and stage of the tumor, with no significant relation with other clinicopathological parameters. AR expression was high in 29% of cases, with significant relation between its expression and each of grade of the tumor and lymph node metastasis. Morphometric results showed a specific positive correlation between Ki-67 proliferation and different AR statuses and also showed a positive significant correlation between Ki-67 and each of PARP-1 and AR immunohistochemical intensity and also degree of AR expression. There was a significant positive correlation between PARP-1 immunohistochemical intensity and AR immunohistochemical intensity.

Conclusion
The current study showed a high positive immunohistochemical expression of PARP-1 in a large percentage of TNBC cases (91%) and AR immunohistochemical expression in a substantial number of cases (29%), as well as a significant positive correlation between PARP-1 immunohistochemical intensity and AR immunohistochemical intensity, which support that both PARP-1 inhibitor and AR antagonist may be potential therapy options in TNBC treatment. The significant correlation noticed in the study between AR-negative immunohistochemical expression of TNBC cases and presence of lymph node metastasis may suggest the possible future role of AR receptors as a prognostic factor in TNBC cases.
The use of bipolar pure cut mode technology in dissection of parotid tumors: A novel technique
Authors: Abou-Ashour Hady , Shahin Mahmoud A. , Shaker Mohamed Nazeh 
Published: August 2023

Background
The basic concern in parotid surgery is facial nerve preservation. Various methods of dissection have been used to excise the parotid tissue and spare the facial nerve and its branches. Combined (blunt, mosquito tip, monopolar, and bipolar electrocautery, and scissor dissection) procedures are the most widely used techniques. Further new methods were used as an alternative for hemostasis and dissection such as ligasure and ultrasonic devices. New emerging technology of bipolar energy with high voltage and low current gave a benefit of deep coagulation and powerful cutting with less spread of heat to the surrounding tissue. In this study, we tried a new dissection technique with the pure auto-cut bipolar electrodissection with the new versions of bipolar technology to report its effect in parotid tumor surgery.
The primary objective of the study was to evaluate the safety and efficacy of new bipolar pure cut electrodissection and weighing its benefits in the preservation of the facial nerve branches and reducing the postoperative complications.
The secondary objective of the study was to compare the result of the new technique with the results of the conventional technique that was previously performed in our department and the complication of this new technique if any.

Patients and methods
This prospective and retrospective study was held in Menoufia University Hospital. Our study included 30 patients with parotid tumors, where 15 retrospective patients underwent conventional parotidectomy (superficial and/or total parotidectomy) and were referred as group B, and 15 prospective patients underwent parotidectomy (superficial or total parotidectomy) and were referred as group A, using the bipolar pure auto-cut electrodissection technique by advanced bipolar technology.

Results
The mean operative time was significantly lower in group A patients than in group B, where the time for superficial parotidectomy was 100±14 min in group A and 117±11 min in group B and for total parotidectomy was 118±12 min in group A and 139±18 min in group B (P=0.001). Regarding postoperative complications, in group A, we reported one case with temporary nerve affection. However, in group B, we reported two cases of wound infection, one case with salivary fistula, two cases with seroma, two cases of temporary nerve affection, two cases of permanent nerve branch affection, and one case of Frey syndrome. Regarding tumor recurrence, we reported only one case in group B.

Conclusions
Using the new bipolar pure cut technique in various types of parotid tumors is technically easier for meticulous fast dissection around the facial nerve branches, showing significantly shorter operative time and less incidence of seroma, wound infection, salivary fistula, and facial nerve injury.