Collagen V Promotes Fibroblast Contractility, And Adhesion Formation, And Stability

Ehlers-Danlos syndrome, classical type, (cEDS) is a hereditary connective tissue disorder causing excessive elasticity and fragility of the connective tissue and problems with wound healing. Most cases of cEDS are caused by haploinsufficiency for collagen V. Collagen V regulates collagen fibril diameter. In cEDS fibroblast migration is impaired and integrin expression is altered. The effects of collagen V on collagen gel ultrastructure and how it alters its mechanical properties were measured using scanning electron microscopy (SEM) and rheology respectively. Fibroblast contractility and adhesion dynamics were investigated to better understand the role of fibroblast disfunction in wound healing in cEDS. To quantify these, traction force microscopy (TFM) and time lapse imaging were used. Collagen V decreased fibril diameter and curvature, and increased gel stiffness, indicating that the fibrils themselves were likely stiffer. Cells cultured on collagen V were more contractile and adhesions assembled faster

Double phase culture system mediated enhanced protocol for shoot proliferation of Vanilla andamanica Rolfe. - an endemic wild relative of commercial Vanilla from the Andaman and Nicobar Islands

A liquid overlay culture system in micropropagation improved shoot proliferation in many species. In the present investigation, we have developed an enhanced shoot proliferation protocol using the double phase culture system (DPS) for Vanilla andamanica, an endemic species of the Andaman and Nicobar Islands recognized under the vulnerable category by the IUCN. In vitro generated nodal explants were used for shoot proliferation experiments and were tested in Murashige and Skoog medium augmented with various cytokinins (BAP, KIN, 2iP) and auxins (IBA, NAA, IAA) to produce a maximum of 3.24 ± 0.08 shoots per explant in 5 µM BAP and 5.23±0.67 roots per shoot in basal MS medium. A remarkable increase in shoot regeneration was observed when the nodal explant was cultured on DPS system with optimum cytokinin (5 µM BAP). On evaluation of the influence of DPS and conventional single-phase systems (SPS), (solid medium) exhibits an improved multiplication rate on a DPS with optimal BAP (5µM) with an average of 8.66 ± 0.17 shoots per explant, which represents a 2-fold increase over the rate of SPS + 5 µM BAP. The plantlets were rooted at 100% frequency in half-strength MS medium devoid of auxins and acclimatized with 100% success. A double-phase mediated enhanced shoot proliferating procedure could be employed for large scale multiplication and commercial breeding trials for better results with regard to V. andamanica

HYPERTENSION IN RELATION TO IMMUNE SYSTEM AND WAY OF LIFE ALONG WITH TREATMENT

The objective of the review is to explain the pathophysiology, different causes and various treatments involved in hypertension. This article discusses the disease's pathogenesis, etiology, diagnosis, and immunity. This review looks at the main significant epidemiological and clinical studies on the role of several lifestyle factors in hypertension development. This review examines the numerous mechanisms that cause hypertension in order to discover new treatments. In addition, it covers the many types of hypertension therapy. According to different studies, lifestyle habits may have an impact on blood pressure levels. Moreover, the importance of chronic inflammation in hypertension and its repercussions has been confirmed in genetically engineered mice lacking components of innate and/or adaptive immunity. Immune cell depletion enhances endothelial function, lowers oxidative stress, lowers the vascular tone, and protects against renal interstitial infiltrates, salt retention, and kidney injury. Based on existing literature, there is strong evidence that lifestyle variables can affect blood pressure levels. Then, in hypertensive people, lifestyle changes can help by lowering overall cardiovascular risk and death from any cause. The involvement of immunity as a common thread in the hypertension processes of many organ systems

Femoropatellar alterations in knees with chronic anterior cruciate ligament injuries: a radiographic analysis

Background: The objective of this study was to correlate the occurrence of patellofemoral malalignment in a chronic anterior cruciate ligament (ACL) deficient knee using common radiological parameters. Methods: A case-control study was conducted on 35 adult patients with previously diagnosed unilateral chronic ACL injury. The injured knee was considered as the case, while the contralateral normal knee served as the control. Radiological parameters including the Caton-Deschamps patellar height index, Merchant patellar congruence angle, and Laurin lateral patellar tilt angle were measured on X-rays obtained from both normal and ACL injured knees. A comparative analysis was performed between the two groups. Results: The Caton-Deschamps patellar height index had a mean value of 0.95±0.05 in the ACL-deficient knee. The Merchant patellar congruence angle showed mean values of 12.66±0.84 degrees in the ACL injured knee, while the Laurin lateral patellar tilt angle was 8.06±1.41 degrees in knees with ACL failure. These results indicate lower patellar height, greater lateral displacement of the patella, and increased lateral patellar tilt in knees with chronic ACL tears, thereby affecting the patellofemoral joint. Conclusions: Chronic ACL tears are associated with patellofemoral malalignment, characterized by decreased patellar height, increased lateral displacement of the patella, and greater lateral patellar tilt, thus impacting the patellofemoral joint

IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment

Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFNγ. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment. Keywords: dendritic cells; homeostasis; differentiation; IFNγ; tumor microenvironment; melanoma tolerance; immunotherapy; suppressor-of-cytokine-signaling 2 (SOCS2); tissue mononuclear phagocyte

Polymerizing actin regulates myosin-independent mechanosensing by modulating actin elasticity and flow fluctuation

The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions. However, it has been unclear if the stiffness-dependent differential tension is induced solely by myosin activity. Here, we report that in the absence of myosin contractility, 3T3 fibroblasts still transmit stiffness-dependent differential levels of traction. This myosin-independent differential traction is regulated by polymerizing actin assisted by actin nucleators Arp2/3 and formin where formin has stronger contribution than Arp2/3. Interestingly, we report a four-fold reduction in traction of cells when both Arp2/3 and myosin were inhibited, compared to cells with only myosin inhibition, while there was only a slight reduction in F-actin flow speed in those cells. We show that the conventional rigid-actin-based clutch model is insufficient to explain this force-flow behavior and requires the inclusion of F-actin’s own elasticity into consideration. Our model prediction suggests that Arp2/3 and formin modulate stiffness sensing via stiffening F-actin network with stronger effect from formin. Analysis of F-actin flow reveals stiffness-dependent fluctuation frequency in the flow speed, which is predictable only via the model considering actin elasticity. Our data and model provide a potential role of the polymerizing actin and its elasticity in myosin-independent mechanosensing

Low Shear in Short-Term Impacts Endothelial Cell Traction and Alignment in Long-Term

Within the vascular system, endothelial cells (ECs) are exposed to fluid shear stress (FSS), a mechanical force exerted by blood flow that is critical for regulating cellular tension and maintaining vascular homeostasis. The way ECs react to FSS varies significantly; while high, laminar FSS supports vasodilation and suppresses inflammation, low or disturbed FSS can lead to endothelial dysfunction and increase the risk of cardiovascular diseases. Yet, the adaptation of ECs to dynamically varying FSS remains poorly understood. This study focuses on the dynamic responses of ECs to brief periods of low FSS, examining its impact on endothelial traction—a measure of cellular tension that plays a crucial role in how endothelial cells respond to mechanical stimuli. By integrating traction force microscopy (TFM) with a custom-built flow chamber, we analyzed how human umbilical vein endothelial cells (HUVECs) adjust their traction in response to shifts from low to high shear stress. We discovered that initial exposure to low FSS prompts a marked increase in traction force, which continues to rise over 10 hours before slowly decreasing. In contrast, immediate exposure to high FSS causes a quick spike in traction followed by a swift reduction, revealing distinct patterns of traction behavior under different shear conditions. Importantly, the direction of traction forces and the resulting cellular alignment under these conditions indicate that the initial shear experience dictates long-term endothelial behavior. Our findings shed light on the critical influence of short-lived low-shear stress experiences in shaping endothelial function, indicating that early exposure to low FSS results in enduring changes in endothelial contractility and alignment, with significant consequences for vascular health and the development of cardiovascular diseases

Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin

The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions, triggering differential mechanoresponses. However, it has been unclear if the stiffness-dependent differential tension is induced solely by myosin activity. Here, we report that in the absence of myosin contractility, 3T3 fibroblasts still transmit stiffness-dependent differential levels of traction. This myosin-independent differential traction is regulated by polymerizing actin assisted by actin nucleators Arp2/3 and formin where formin has a stronger contribution than Arp2/3 to both traction and actin flow. Intriguingly, despite only slight changes in F-actin flow speed observed in cells with the combined inhibition of Arp2/3 and myosin compared to cells with sole myosin inhibition, they show a 4-times reduction in traction than cells with myosin-only inhibition. Our analyses indicate that traditional models based on rigid F-actin are inadequate for capturing such dramatic force reduction with similar actin flow. Instead, incorporating the F-actin network’s viscoelastic properties is crucial. Our new model including the F-actin viscoelasticity reveals that Arp2/3 and formin enhance stiffness sensitivity by mechanically reinforcing the F-actin network, thereby facilitating more effective transmission of flow-induced forces. This model is validated by cell stiffness measurement with atomic force microscopy and experimental observation of model-predicted stiffness-dependent actin flow fluctuation