HISTOLOGY AND HISTOPATHOLOGY

The methyltransferase KIAA1429 potentiates cervical cancer tumorigenesis via modulating LARP1 mRNA m6A modification and stability
Feng X and Shu L
Cervical cancer (CC) is one of the most common gynecological malignancies in the world and poses a great threat to public health. There is inadequate knowledge of the molecular mechanisms underlying CC. This study aimed to explore the prognostic value of KIAA1429 (VIRMA, vir-Like m6A methyltransferase associated) in patients with CC and analyze its molecular mechanisms. The level of KIAA1429 in tumor specimens was tested using RT-qPCR and western blotting. Cellular biological processes were assessed using CCK-8 and Transwell assays. Xenograft experiments were used to verify the function of KIAA1429 in CC . The results manifested that KIAA1429 expression was enhanced in CC. Downregulation of KIAA1429 hindered the viability, migration, and invasion of CC cells. Moreover, LARP1 (La-related protein 1) was uncovered to be positively modulated by KIAA1429. Further, the anti-tumor impacts of KIAA1429 depletion on the phenotype of CC cells were counteracted by LARP1 amplification. Additionally, KIAA1429 deficiency suppressed the stability of LARP1 through methylating LARP1. Collectively, KIAA1429 can boost the tumorigenesis of CC via modifying LARP1 through m6A methylation to promote its stability. This work highlights the promoting effects of KIAA1429 on CC development and presents new targets for its treatment.
Identification of new tissue markers for the monitoring and standardization of penile cancer according to the degree of differentiation
Casanova-Martín C, Liviu Boaru D, Fraile-Martinez O, Garcia-Montero C, De Leon-Oliva D, De Castro-Martinez P, Gimeno-Longas MJ, Bujan J, García-Honduvilla N, Guijarro LG, Gragera R, Lopez-Gonzalez L, Saez MA, Ferrara-Coppola C, Baena-Romero V, Diaz-Pedrero R, Alvarez-Mon M, Toledo-Lobo MV and Ortega MA
Penile cancer is an uncommon disease compared with other urological tumors and is more common in low- and middle-income countries. Risk factors include age, ethnicity, smoking, hygiene, and human papillomavirus infection. Although carcinoma of the penis can be cured in up to 80% of cases if detected early, late diagnosis drastically reduces survival rates, especially in metastatic cases. More than 95% of cases are squamous cell carcinomas, and the degree of cell differentiation is a key histopathological factor, distinguishing between poorly (P), moderately (M), and well-differentiated (W) carcinomas, with verrucous carcinoma (V) having the best prognosis due to its low metastatic capacity. This study analyses the differential expression of several biomarkers related to cell proliferation and cell cycle, inflammation, epigenetics, and autophagy (cell cycle (IRS-4, Ki-67, RB1, CDK4, cyclin D1, ERBB2, β-catenin, and MAGE-A), inflammation (COX2, NLRP3, and AIF-1), epigenetics (HAT-1) and autophagy (ULK-1 and ATG9A) in penile carcinoma according to the degree of differentiation. Immunohistochemical techniques were performed on 34 penile squamous cell carcinoma (PSCC) samples classified into subtype V (N=6), and groups P (N=9), M (N=9), and W (N=10). The findings suggest a differential expression of molecules according to the degree of cell differentiation, with a higher differential expression of molecules according to the degree of cell differentiation, suggesting that the proteins studied could have predictive value. The study highlights the complexity of PSCC and the need for future studies to explore translational applications and search for new biomarkers to improve clinical management and understanding of this disease.
Expression and prognostic value of PIM-1 kinase in gliomas
Li Z, Wang H, Wang G, Zhang A, Wang C, Mo L, Jia Z and Tong X
This study aimed to explore the correlation of PIM-1 with the clinicopathological features and prognosis of patients.
Paeonol regulates glycolytic metabolism by downregulating BACH1 to ameliorate stemness, angiogenesis, and EMT in SiHa cervical cancer cells
Sheng S, Xu J, Hu D, Qian W, Xu X and He J
As a common reproductive malignancy of the female reproductive system, cervical cancer has increasingly become a public health concern. Paeonol, which is a natural phenolic monomer, has been found to possess substantial anticancer effects in some human cancers. The present study was conceived to explore the role and mechanism of paeonol in cervical cancer. Initially, the cytotoxicity of paeonol on immortalized H8 cervical epithelial cells and the proliferation of SiHa cervical cancer cells with paeonol treatment were detected using the CCK-8 assay. Cell stemness was assessed with the spheroid formation assay while western blot was applied for the measurement of proteins associated with cell stemness. The tube formation assay was used to detect the angiogenesis of human umbilical vein endothelial cells (HUVECs) and western blot was used to estimate the expression of EMT- and angiogenesis-related proteins. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of cells were appraised via a Seahorse XFe24 Flux Analyzer. Lactate production, glucose consumption, and ATP levels were evaluated with corresponding assay kits. Western blot was applied for the evaluation of GLUT1 and HK2. The mRNA and protein expression of BACH1 before and after transfection were detected using RT-qPCR and western blot. The luciferase reporter assay was used to detect the activities of GLUT1 and HK2 promoters. In this study, we found that paeonol inhibited cell proliferation, cell stemness, EMT progress, angiogenesis, and glycolysis in cervical cancer via downregulating BACH1. In summary, paeonol impeded the progression of cervical cancer by regulating glycolytic metabolism through the inhibition of BACH1.
Phosphorylated protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) expression in breast cancer is correlated with malignant proliferation and histological grading
Yang X, Duan S, Zha J, Jiang T, Ye C and Yu S
This study aims to detect the expression of phosphorylated PERK in breast cancer using immunohistochemistry and explore its significance. We examined 134 cases of formalin-fixed and paraffin-embedded breast cancer tissues. It was found that the expression of phosphorylated PERK in ductal carcinoma was higher than that in lobular carcinoma, and the difference between them was statistically significant, suggesting that phosphorylated PERK played different roles in the occurrence and development of different types of breast cancer. Compared with Ki-67-negative breast cancer tissues, phosphorylated PERK has higher expression in Ki-67-positive tissues and is positively correlated with Ki67 expression, indicating that phosphorylated PERK plays an important role in breast cancer's malignant proliferation and progression. We also found a positive correlation between phosphorylated PERK expression and the histological grading of invasive ductal carcinoma, indicating that phosphorylated PERK plays an important role in the differentiation of invasive ductal carcinoma. Our study revealed the differential expression of phosphorylated PERK in subtypes of breast cancer. It contributed to the malignant proliferation of breast cancer and tissue differentiation of invasive ductal carcinoma of the breast.
Assessing the expression of Nectin-4 in solid tumors by immunohistochemistry - what do we know?
Sanders C and Kristiansen G
Antibody-Drug Conjugates (ADCs) represent a promising class of anti-cancer substances that combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs, hence they enable a new approach of targeted therapy. The use of the ADC Entfortumab Vedotin (EV), which targets the viral receptor Nectin-4, showed an impressive clinical response in metastatic urothelial carcinoma. In this review, we present what is known about the expression of Nectin-4 in various tumor entities, focusing on immunohistochemistry as a diagnostic venue to detect positive expression, as this inexpensive technique is readily available in pathology laboratories. Various studies demonstrated expression of Nectin-4 in many solid tumor entities with the highest expression rates in urothelial carcinomas and breast cancer. To date, the relevance of the subcellular compartment of immunoreactivity (membranous vs. cytoplasmic) is still unclear in respect of its predictive value for EV therapy, which ought to be clarified in further studies.
Hsa_circ_0088036 promotes tumorigenesis and chemotherapy resistance in hepatocellular carcinoma via the miR-140-3p/KIF2A axis
Wang Z, Wang L, Yin G, Li H, Zhang R, Feng Y and Chang W
Hepatocellular carcinoma (HCC) is a cancer with high morbidity and mortality. There are limited treatment options, particularly for chemotherapy-resistant HCC patients. Circular RNA hsa_circ_0088036 was associated with the development of bladder cancer and non-small cell lung cancer. However, whether it might be a potential therapeutic target for HCC remains elusive.
Melatonin inhibits the activation of microglia and cough sensitivity of guinea pigs exposed to PM2.5
Zhang S, Long L, Chai S, Lin M, Lu H, Liu X, He Y, Dong R and Chen Z
The study aimed to examine the impact of melatonin on mitigating brain inflammation and cough sensitivity resulting from exposure to particulate matter 2.5 (PM2.5).
Impact of 6-OHDA injection and microtrauma in the rat on local brain amyloid beta protein concentrations in the affected area
Roldán-Kalil JA, Vendrell-Gonzalez SE, Espinosa-Ponce N, Colón-Vasques J, Ortiz-Rivera J, Tsytsarev V, Alves JM and Inyushin M
Amyloid beta peptides (Aβ) are key indicators of Alzheimer's disease and are also linked to cognitive decline in Parkinson's disease (PD) and other neurodegenerative disorders. This study explored the accumulation of Aβ in a standard 6-Hydroxydopamine (6-OHDA) model of PD. We unilaterally injected 6-OHDA into the of Wistar rats to induce dopaminergic cell degeneration and death, a characteristic of PD. The goal was to detect Aβ protein in tissues and blood vessels showing inflammation or degeneration from the 6-OHDA injection. Our results showed that 6-OHDA injection produced a statistically significant rise in Aβ concentration at the injection site 60 minutes after injection, which was slightly reduced 24 hours post-injection but still significantly higher than in controls. We also tried Gp120 injection in the same zone but it only produced effects comparable to control needle trauma. The presence of Aβ in tissues and blood vessel walls after injection was confirmed through ELISA tests and was supported by immunohistochemical staining of injection areas. We found that the increased Aβ concentration was visible in and around blood vessels and inside blood vessel walls, and also, to a lesser extent in some cells, most probably neurons, in the area. This research highlights the connection between dopaminergic cell poisoning and the accumulation of Aβ, offering insights into the progression of PD to cognitive disorders and dementia.
Experimental murine models of interstitial cystitis/bladder pain syndrome: A review
Saito T, Minagawa T, Yoshimura N, Luo Y and Akiyama Y
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic enigmatic disease of the urinary bladder characterized by persistent bladder/pelvic pain in conjunction with lower urinary tract symptoms. IC/BPS is categorized as either Hunner-type IC (HIC) or BPS based on the presence/absence of the Hunner lesion, a reddish mucosal lesion in the bladder. HIC and BPS present with similar symptoms, however, the etiologies are completely different. Recent evidence suggests that HIC is an immune-mediated inflammatory disease of the urinary bladder. In contrast, BPS, other forms of HIC lacking Hunner lesions, is a minimally inflamed condition comprising various clinical phenotypes. Based on this evidence, basic research into IC/BPS has shifted to target each subtype of IC/BPS. Today, experimental murine models of autoimmune cystitis are used for HIC research, whereas models related to neurophysiological and psychosocial dysfunctions have been developed for BPS research. This emerging concept of a subtype-tailored approach may contribute to a better understanding of the full picture of IC/BPS, thereby improving current clinical management strategies and the development of novel therapies.
Ferroptosis: A key regulator and potential target for tissue injury
Liu R, Luo Q and Song G
The maintenance of iron homeostasis is essential for proper body function. A growing body of evidence suggests that iron imbalance is the common denominator in many tissue injuries, including acute, chronic, and reperfusion injuries. Ferroptosis, a novel form of programmed cell death due to metabolic abnormalities, has become increasingly recognized as an important process mediating the pathogenesis and progression of numerous tissue injuries, including cerebral, myocardial, lung, liver, kidney, and intestinal injuries. Therefore, a thorough understanding of the mechanisms involved in the regulation of ferroptosis might contribute to improvements in disease management. In this review, we summarize the importance of ferroptosis in various tissue injuries, discuss the potential targets of ferroptosis in the treatment of tissue injuries, and describe the current limitations and future directions of these novel treatment targets.
Aerobic exercise remodels gut microbiota to alleviate cerebral ischemia-reperfusion injury
Zhu M, Zhu J, Pan J, Fu R, Pan G and Zhang J
Aerobic exercise exhibits a neuroprotective role against cerebral ischemia-reperfusion (I/R) injury, and the present study explored the underlying mechanisms. Adult Sprague-Dawley rats (n=87) were used in the study, and cerebral I/R injury in rats was modeled using middle cerebral artery occlusion and reperfusion (MCAOR), followed by interval aerobic exercise training at a moderate intensity. Colonization with gut microbiota from the trained rats was performed on MCAOR rats. Neurobehavioral assessments were performed. Cerebral infarction and neuronal damage were detected by tissue staining and molecular experiments. Gut microbiota composition was analyzed by 16S rRNA gene sequencing. Neuroinflammation was detected using an enzyme-linked immunosorbent assay. Aerobic exercise ameliorated neurological deficit, spontaneous locomotor activity, and spatial learning and memory impairment in MCAOR rats (<0.001). Further, aerobic exercise decreased infarct volume, attenuated neuronal damage, increased SYN1 and PSD95 expression, as well as reduced neuroinflammation by upregulating IL-10 and downregulating IL-6, TNF-α, IL-17, and TGF-β in MCAOR rats (<0.05). Aerobic exercise altered gut microbiota composition in MCAOR rats. Gut microbiota colonization in rats alleviated cerebral I/R injury by reducing neurological deficit scores, promoting spontaneous locomotor activity, decreasing infarct volume, elevating SYN1 and PSD95 expression, and improving neuroinflammation (<0.05). In conclusion, aerobic exercise remodeled the gut microbiota in rats to attenuate cognitive dysfunction and neuroinflammation after cerebral I/R.
Does old-to-young kidney transplantation rejuvenate old donor kidneys?
Takahashi-Kobayashi M, Kawanishi K, Usui J, Yamazaki S, Seshan SV and Yamagata K
The number of older organ donors is increasing due to the aging population. Aged kidneys often face problems such as delayed graft function but previous murine experiments suggested the possibilities of rejuvenation, for example, in a parabiosis setting between old and young mice. To investigate kidney-graft rejuvenation, we compared an old-to-young (O-Y) patient transplantation group and a transplantation group with donors/recipients of approx. the same age (SA) with the renal senescence marker p16 in kidney biopsy samples at baseline and one year post-transplantation.
The role of the Ki-67 labelling index as an independent prognostic factor in indonesian glioma patients
Dwianingsih EK, Pranacipta S, Theresia E, Safitri S, Hartanto RA and Malueka RG
Gliomas are the most common type of brain tumor. However, interpreting glioma morphology is subjective, and identifying mitosis can be challenging. This can impact the determination of the patient's tumor grade, therapy, and prognosis. In addition, the Ki-67 expression level, which reflects the tumor cells' ability to proliferate, is closely related to the patient's survival. This study aims to find a correlation between Ki-67 expression and the overall survival (OS) of glioma patients in the Indonesian population.
USP33 promotes pulmonary microvascular endothelial cell pyroptosis by stabilizing TRAF2 through deubiquitination
Liang J, Chen J and Xu P
Inhibiting the pyroptosis of human pulmonary microvascular endothelial cells (HPMECs) is a promising therapeutic modality for acute lung injury (ALI). Given the undefined effect of ubiquitin-specific protease 33 (USP33) and tumor necrosis factor receptor-associated factor 2 (TRAF2) on pyroptosis in lung injury, this study investigates their roles in the pyroptosis of HPMECs during ALI.
E2F1-induced upregulation of contributes to endometrial cancer progression
Wang S, Sun Y, Guo M, Zhu P and Xin B
To investigate the role of Trophinin-associated protein (TROAP) in endometrial cancer (EC) progression and elucidate how the transcription factor E2F transcription factor 1 (E2F1) modulates EC by upregulating expression.
Biomechanical and histological analyses of a multilayer stent in a swine model of suprarenal aortic aneurysm
Tobita AM, Strazzi APWB, Portugal MFC, Wolosker N, Aun R, Monteiro FLJ, da Silva ES and Sincos IR
To analyze and compare, in an animal model, the treatment of thoracoabdominal aneurysms with multilayer stents and its hemodynamic effects through the biomechanical and histological analysis of the aortic wall in contact with the stent.
Associations between BCL-2 expression and different histopathological prognostic factors in different molecular subtypes of invasive breast carcinoma of no special type
Hassan WA, El-Assmy M, ElBanna AK, Harbieh I, Noufal N, Lotfy H, Shemais TAH, Haikal OA, Saber MM and Ali RI
Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to the unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein, has been proposed as a marker of poor prognosis, associated with resistance to therapy in most tumor types expressing BCL-2. In breast cancer, however, BCL-2 expression has been reported to be a favorable prognostic factor. This study aimed to describe the association between BCL-2 and other well-known pathological prognostic markers among different molecular sub-types of invasive breast carcinoma of no special type (IBC; NST).
Fortunellin attenuates sepsis-induced acute kidney injury by inhibiting inflammation and ferroptosis via the TLR4/NF-κB pathway
Zhang Y, Liu T and Zuo Z
To investigate the potential protective effect of fortunellin in sepsis-induced acute kidney injury (AKI) and its underlying mechanisms.
Clinicopathological diagnosis of axillary signet-ring cell-like/histiocytoid carcinoma: a case report and literature review
Zhang L, Li L, Wang Y and Wang XL
To explore the clinicopathological and morphological characteristics, diagnosis, differential diagnosis, treatment, and prognosis of primary signet-ring cell/histiocytoid carcinoma (SRCHC) of the axilla.
Time course analysis of changes in neuronal loss, oxidative stress, and excitotoxicity in gerbil hippocampus following ischemia and reperfusion under hyperthermic conditions
Lee TK, Kim DW, Park JH, Lee CH, Yang SR, Shin MC, Won MH, Cho JH and Ahn JH
Oxidative stress and excitotoxicity are the major causes of neuronal death/loss in the brain following ischemia and reperfusion (IR). Hyperthermia is known to exacerbate ischemic neuronal damage; however, the underlying mechanisms remain unclear. This study investigated the mechanisms underlying neuronal damage caused by IR injury (IRI) under hyperthermic conditions in the gerbil hippocampal CA1 region. Gerbils were controlled at normothermia (37.5±0.2°C) or hyperthermia (39.5±0.2°C). After temperature control for 30 min, the animals received IRI (following 5 min of transient forebrain ischemia) or sham ischemia, and were subsequently sacrificed at 0, 3, 6, 12, 24, 48, and 120h after IRI. Neuronal death was examined using neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence. Oxidative stress was analyzed by immunohistochemistry for 8-Hydroxy-2'-deoxyguanosine (8OHdG) and superoxide dismutase 2 (SOD2). Excitotoxicity was investigated by immunohistochemistry and western blotting for glutamate transporter 1 (GLT1). Immunohistochemical staining for glial fibrillary acidic proteins (GFAP) was performed to detect reactive astrogliosis. Loss of pyramidal neurons was detected earlier (48h post-IRI) in the hyperthermia-IRI group than in the normothermia-IRI group (120h post-IRI). Further, 8OHdG and SOD2 immunoreactivity in the hyperthermia-IRI group was significantly higher than that in the normothermia-IRI group. Changes in GLT1 immunoreactivity in both groups were biphasic, indicating that the immunoreactivity and protein levels were significantly lower in the hyperthermia-IRI group. GFAP immunoreactivity was enhanced following neuronal loss, indicating that the immunoreactivity was significantly higher in the hyperthermia-IRI group. Taken together, these results suggest that brain IR under hyperthermic conditions can aggravate neuronal damage in the hippocampal CA1 region through severe oxidative stress and excitotoxicity.