Dynamics of morphological manifestations of the experimental acute aspiration bronchopneumonia development.

Background. Currently, there is a need to create an experimental model for reproducing the main pathogenetic mechanisms of COVID-associated lungs damage. The first stage of such a model may be reproducing acute aspiration bronchopneumonia in rats. Objective. Examine the dynamics of morphological changes in the lungs in the development of experimental acute aspiration bronchopneumonia. Methods. The group of laboratory Wistar rats (n=25) in compliance with bioethical norms under typoental anesthesia was carried out operational intervention with the introduction of a sterile capron thread 2.5 cm long and a thickness of 0.2 mm to a depth of 2.5 cm. In the control group included 5 false-controlled animals. At 7, 14, 21, 28 and 56 days, the animals were derived from the experiment, morphological studies were carried out with the painting serial sections with hematoxylin-eosin. Results. On the 7 day, the morphological picture testified to the development of the acute stage of exudative inflammation with the full-blood of vessels, microtrombosis, dyslectasis, hyperplasia of alveolocytes II type. After 14 days, the proliferative stage was formed with alveolocytes hyperplasia, the epithelium of bronchi, as well as fibroblasts with the formation of sharp peribronchial and alveolar abscesses. After 21 days, the development of the lungs fibrosis with the organization of acute peribronchial and alveolar abscesses was noted, peribronchial and intraalveoli pronounced interstitial edema and the reactive hyperplasia of lymphoid follicles of a mixed nature. After 28 days, bronchopneumonia was organized in the form of fibrosis parenchyma, sections of chronic productive inflammation with the formation of resorbative granuloms; sections of the blood vessels hyalinose. For 56 days, these phenomena were progressed before the development of dense fibrosis (carnification) with sections of chronic abscesses with a formed by a connective tissue capsule, the development of vascular hyalinose. Conclusion. Thus, the model of acute aspiration bronchopneumonia reproduces the dynamics of morphological manifestations of acute lung damage, which is the basis for the development of pathogenetic therapy fields.

What Is a Solitary Keratoacanthoma? A Benign Follicular Neoplasm, Frequently Associated with Squamous Cell Carcinoma

We present histopathological criteria for diagnosing keratoacanthoma (KA). In KA, four histological stages are recognized, which are the early/proliferative stage, well-developed stage, regressing stage and regressed stage. In diagnosing KA, we emphasize that KA consists of the proliferation of enlarged pale pink cells with ground glass-like cytoplasm without nuclear atypia, other than crateriform architecture. KA sometimes exhibits malignant transformation within the lesions. We describe the characteristics of benign and malignant epithelial crateriform tumors that should be differentiated from KA. We also present the data of histopathological diagnosis of lesions clinically diagnosed as KA, its natural course and related lesions after partial biopsy, and incidence of crateriform epithelial neoplasms. Based on these data, we recommend complete excision of the lesion when KA is clinically suspected, especially when the lesion is located on a sun-exposed area of an elderly patient. If complete excision is impossible, partial excision of a sufficient specimen with intact architecture is required. In such a case, however, careful investigation after biopsy will be needed, even if the histopathological diagnosis is KA, because there is some possibility that a conventional SCC lesion remains in the residual tissue.

Retinal vasculitis – Clinical manifestations and outcome at tertiary eye care centre in south India

To study the various causes, clinical presentation, management and outcome of the retinal vasculitis cases at tertiary eye care centre. Tertiary eye care centre, Telangana State, South India. Retrospective Interventional Study. Jan 2016 to Dec 2020. Fifty one patients of retinal vasculitis presented with various clinical manifestations were examined in detail and managed. Data collected from medical records. All young patients of different age group presented with retinal vascular changes are included in the study. Patients underwent examination and laboratory workup. Few patients showed ocular and systemic investigations were with in the normal limits. These patients were considered as idiopathic cases. BCVA, slit lamp examination, fundus examination, FFA, OCT, B SCAN in hazy media and documentation done in all cases. Bilateral presentation was common, some presented with aggressive disease in both eyes (early and delayed presentation). Common presentation was blurred vision and sudden drop of vision. Few patients showed tuberculin skin test positive and managed as presumed ocular tuberculosis. Patients who were HIV positive managed with HART, prognosis was poor in these patients. Medical and surgical management done based on the stage of presentation, oral steroids, laser therapy, anti VEGF followed by pars plana vitrectomy with or with silicone oil tamponade done. Oral steroids were started after physician clearance and tapered based on the activity of the disease. Patients followed regularly every month till the activity ceases in medically managed cases and in operated cases we followed till the silicone oil is removed from the eye. Few patients presented with the reactivity of the disease were managed again based on the presentation. Results were good in idiopathic cases, patients presented with inflammatory and ischemic stages also showed good outcome. Patients presented with proliferative stage showed fair outcome, patients presented with severe proliferative stage showed poor prognosis. Retinal vasculitis is one of the ocular condition which can cause vision loss in young adults, if present in early stage, can be managed medically. Prognosis is good in early stages. Recurrent vitreous haemorrhage, tractional retinal detachment, combined retinal detachment were common presentations. Infective cases showed more proliferative changes. Risk of neovascular glaucoma is one of the cause of blindness.

Elevated miR-10a-5p facilitates cell cycle and restrains adipogenic differentiation via targeting Map2k6 and Fasn, respectively

miRNAs are a small class of noncoding RNAs that perform biological functions by regulating the stability or translation of target genes in various biological processes. This study illustrated the role of miR-10a-5p, which is relatively enriched in adipose tissues, using primary mouse preadipocytes as model. With elevated miR-10a-5p expression, the proliferative ability of mouse preadipocytes was significantly enhanced, indicated by increased EdU+ cells and G1/S transition, accompanied by upregulated Cyclin B, Cyclin D and PCNA and downregulated p21 and p27. Meanwhile, the adipogenic differentiation was significantly attenuated by elevated miR-10a-5p, supported by Oil Red O staining and suppressed PPARγ and aP2 expression. Furthermore, Map2k6 and Fasn were predicted to be the target genes of miR-10a-5p in silico, and dual luciferase reporter assay confirmed the direct targeting effects. Western blot analysis results showed that miR-10a-5p specially reduced Map2k6 expression at the proliferative stage without affecting Fasn expression, while significantly restrained Fasn expression with unchanged Map2k6 expression during adipogenic differentiation. Taken together, these results revealed a potential role of miR-10a-5p in adipogenesis and in the treatment of obesity.

High-resolution architecture of human epiphysis formation

SummaryHuman limb skeletal system consists of both bone and cartilage which originated from fetal cartilage. However, the roadmap of chondrocyte divergent differentiation to bone and articular cartilage has yet to be established. Epiphysis possesses articular cartilage, growth plate and the secondary ossification center (SOC), making it an ideal model to uncover the trajectory of chondrocyte divergent differentiation. Here, we mapped differentiation trajectory of human chondrocyte during postnatal finger epiphysis development by using single-cell RNA sequencing. Our results uncovered that chondroprogenitors have two differentiation pathways to hypertrophic chondrocytes during ossification, and one pathway to articular chondrocytes for formation of cartilages. Interestingly, we found that, as an addition to the known typical endochondral ossification path from resting, proliferative to hypertrophic chondrocytes, there was a bypass by which chondroprogenitors differentiate into hypertrophic chondrocytes without proliferative stage. Furthermore, our results revealed two new chondrocyte subpopulations (bypass chondrocytes as it appeared in the ossification bypass, and ID1+ chondroblasts in articular chondrocyte path) during postnatal epiphysis development in addition to six well-known subpopulations. Overall, our study provides a comprehensive roadmap of chondrocyte differentiation in human epiphysis thereby expanding the knowledge of bone and articular cartilage, which could be utilized to design biotherapeutics for bone and articular cartilage regeneration.

Epo receptor signaling in macrophages alters the splenic niche to promote erythroid differentiation

Anemic stress induces stress erythropoiesis, which rapidly generates new erythrocytes to restore tissue oxygenation. Stress erythropoiesis is best understood in mice where it is extramedullary and occurs primarily in the spleen. However, both human and mouse stress erythropoiesis use signals and progenitor cells that are distinct from steady-state erythropoiesis. Immature stress erythroid progenitors (SEPs) are derived from short-term hematopoietic stem cells. Although the SEPs are capable of self-renewal, they are erythroid restricted. Inflammation and anemic stress induce the rapid proliferation of SEPs, but they do not differentiate until serum erythropoietin (Epo) levels increase. Here we show that rather than directly regulating SEPs, Epo promotes this transition from proliferation to differentiation by acting on macrophages in the splenic niche. During the proliferative stage, macrophages produce canonical Wnt ligands that promote proliferation and inhibit differentiation. Epo/Stat5-dependent signaling induces the production of bioactive lipid mediators in macrophages. Increased production of prostaglandin J2 (PGJ2) activates peroxisome proliferator-activated receptor γ (PPARγ)-dependent repression of Wnt expression, whereas increased production of prostaglandin E2 (PGE2) promotes the differentiation of SEPs.

Early Photocoagulation for Diabetic Retinopathy

The Early Treatment Diabetic Retinopathy Study (ETDRS) was a randomized clinical trial involving nearly four thousand diabetic patients with early proliferative retinopathy, moderate to severe nonproliferative retinopathy, and/or diabetic macular edema in each eye. This paper (ETDRS report number 9) examined the question of when in the course of diabetic retinopathy it is most effective to initiate photocoagulation therapy. Based on the study findings, the authors recommended that panretinal scatter photocoagulation not be carried out in eyes with mild or moderate nonproliferative diabetic retinopathy; when retinopathy is more severe, however, panretinal scatter photocoagulation usually should not be delayed if the eye has reached the high-risk proliferative stage. Focal treatment should be considered for eyes with macular edema that involves or threatens the center of the macula, preferably before scatter photocoagulation for high-risk proliferative retinopathy becomes urgent.