Blebology: principles of bleb-based migration.

Bleb-based migration, a conserved cell motility mode, has a crucial role in both physiological and pathological processes. Unlike the well-elucidated mechanisms of lamellipodium-based mesenchymal migration, the dynamics of bleb-based migration remain less understood. In this review, we highlight in a systematic way the establishment of front-rear polarity, bleb formation and extension, and the distinct regimes of bleb dynamics. We emphasize new evidence proposing a regulatory role of plasma membrane-cortex interactions in blebbing behavior and discuss the generation of force and its transmission during migration. Our analysis aims to deepen the understanding of the physical and molecular mechanisms of bleb-based migration, shedding light on its implications and significance for health and disease.

Addressing Oral Health Disparities of a Tribal Population Through a Combined Implementation of Focus Group Discussion, Mobile Technology Networking, and Creating a Supportive Environment: A Prospective Study.

BACKGROUND AND OBJECTIVE:  Oral health disparities generally exist among tribal populations, prompting creative solutions to tackle these challenges. By using a combined implementation strategy of including focus group discussion (FGD), mobile technology networking (MTN), and creating a supportive environment, this study aims to assess and bring positive changes in oral health in these populations. METHODS: The current study employed a mixed-method approach on a sample of 100 tribal volunteers. Qualitative assessment included FGD conducted regularly for three months based on themes such as oral hygiene habits, access to oral health, technology in oral health, the relationship of oral health to general health, and the role of diet in oral health. Quantitative evaluation included recording of the oral hygiene index-simplified and gingival index to measure gingival status. Messages on oral health were routinely posted to mobile phones to reinforce oral health education. Appropriate use of indigenous oral hygiene aids (neem and datun) was also taught during the discussion session. Clinical examinations were compared before and after FGD. Data were analyzed using IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States). A paired 't' test was used to find significant differences in gingival status at p<0.05. RESULTS: The FGD sessions deduced observations such as limited access to dental care, inadequate oral hygiene practices such as usage of neem sticks and twigs, and lack of oral health awareness. The implementation of MTN facilitated the dissemination of oral health information and enhanced communication between community members and healthcare providers. The gingival index score significantly improved from pre-FGD to post-FGD with a mean difference of 0.41700 significant at p=0.000. Oral hygiene of the target population shifted from "Fair" oral hygiene status to "Good" oral hygiene status. CONCLUSION: The combined implementation of FGD, MTN, and creation of a supportive environment demonstrated promising results in addressing oral health disparities among the tribal population. The interventions led to improved gingival status and better utilization of oral hygiene practices. These findings highlight the importance of tailored interventions, community engagement, and mobile technology in addressing oral health disparities in tribal populations. Ongoing support, sustainability, and further research are necessary to ensure the long-term impact and effectiveness of these interventions.

The role of guggulsterone on the NF-κB pathway in inflammatory bowel disease: preclinical evidence.

Guggulsterone, a phytosterol in the herb Commiphora wightii (Arn.) Bhandari, has been used in the treatment of diseases such as hyperlipidemia, arthritis and atherosclerosis. It has attracted significant research interest because of its pharmacological properties, especially its anti-inflammatory nature. It can be used for the treatment of inflammatory bowel disease (IBD), a disease characterized by chronic inflammation and damage in the gastrointestinal tract. In various preclinical studies, it inhibited NF-κB, an important pathway in the pathophysiology of IBD. This review summarizes the preclinical studies on this topic for providing more insights to the mechanism by which guggulsterone exerts its effect.

Pharmacological intervention in oxidative stress as a therapeutic target in neurological disorders.

OBJECTIVES: Oxidative stress is a major cellular burden that triggers reactive oxygen species (ROS) and antioxidants that modulate signalling mechanisms. Byproducts generated from this process govern the brain pathology and functions in various neurological diseases. As oxidative stress remains the key therapeutic target in neurological disease, it is necessary to explore the multiple routes that can significantly repair the damage caused due to ROS and consequently, neurodegenerative disorders (NDDs). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the critical player of oxidative stress that can also be used as a therapeutic target to combat NDDs. KEY FINDINGS: Several antioxidants signalling pathways are found to be associated with oxidative stress and show a protective effect against stressors by increasing the release of various cytoprotective enzymes and also exert anti-inflammatory response against this oxidative damage. These pathways along with antioxidants and reactive species can be the defined targets to eliminate or reduce the harmful effects of neurological diseases. SUMMARY: Herein, we discussed the underlying mechanism and crucial role of antioxidants in therapeutics together with natural compounds as a pharmacological tool to combat the cellular deformities cascades caused due to oxidative stress.

Regulatory mechanism of cyclins and cyclin-dependent kinases in post-mitotic neuronal cell division.

Neurodegenerative diseases (NDDs) are the most common life-threatening disease of the central nervous system and it cause the progressive loss of neuronal cells. The exact mechanism of the disease's progression is not clear and thus line of treatment for NDDs is a baffling issue. During the progression of NDDs, oxidative stress and DNA damage play an important regulatory function, and ultimately induces neurodegeneration. Recently, aberrant cell cycle events have been demonstrated in the progression of different NDDs. However, the pertinent role of signaling mechanism, for instance, post-translational modifications, oxidative stress, DNA damage response pathway, JNK/p38 MAPK, MEK/ERK cascade, actively participated in the aberrant cell cycle reentry induced neuronal cell death. Mounting evidence has demonstrated that aberrant cell cycle re-entry is a major contributing factor in the pathogenesis of NDDs rather than a secondary phenomenon. In the brain of AD patients with mild cognitive impairment, post miotic cell division can be seen in the early stage of the disease. However, in the brain of PD patients, response to various neurotoxic signals, the cell cycle re-entry has been observed that causes neuronal apoptosis. On contrary, the contributing factors that leads to the induction of cell cycle events in mature neurons in HD and ALS brain pathology is remain unclear. Various pharmacological drugs have been developed to reduce the pathogenesis of NDDs, but they are still not helpful in eliminating the cause of these NDDs.

Estimation and Correlation of MMP-8 Levels in GCF and Serum with Wound Healing and Clinical Outcomes of Coronally Advanced Flap and Sub-Epithelial Connective Tissue Graft for Root Coverage - A Controlled Clinical Trial.

BACKGROUND AND OBJECTIVES: The success of any surgical procedure is predominately influenced by the pattern of its wound healing. The objective of the present study was to assess gingival crevicular fluid (GCF) and serum matrix metalloproteinase-8 (MMP-8) levels during the early healing phase of root coverage procedures. MMP-8 levels on days four and seven were correlated with the wound healing index (WHI) to evaluate the presence of MMP-8 during early post-surgical wound healing after root coverage procedures. MATERIALS AND METHODS: Fifteen isolated maxillary Miller's Class I/Class II recession defects in systemically and periodontally healthy patients in the age range of 25 - 57 years were treated with coronally advanced flap and sub-epithelial connective tissue graft (CAF + SCTG). GCF and serum samples were collected at baseline, day four, day seven and six months after surgery from the gingival sulcus of the recession defect. A contralateral tooth with clinically healthy gingiva was used as control and samples were collected from this site too at the same time intervals. MMP-8 levels in GCF and serum were measured using enzyme-linked immunosorbent assay (ELISA). Wound Healing Index was assessed on days four and seven. Mean root coverage (MRC) and complete root coverage (CRC) were assessed six months post-operatively. RESULTS: Statistically signifi cant reduction in recession depth was observed with MRC of 88.67%. GCF and serum MMP-8 levels were significantly elevated on days four and seven post-surgery (p less than 0.001) in the test site and reduced to baseline levels after six months. Weak positive correlation was observed between wound healing index and GCF MMP-8 levels on days four and seven. Moderate positive correlation was noted between serum MMP-8 levels and root coverage outcomes. However, this correlation was not statistically signifi cant (p greater than 0.05). CONCLUSION: The present prospective study showed satisfactory post-surgical healing and root coverage outcome. MMP-8 levels and its increase/decrease during the early wound healing follows the expected temporal pattern. No significant correlation was noted between MMP-8 levels during early wound healing and root coverage outcomes.

Quantitative Control of GPCR Organization and Signaling by Endocytosis in Epithelial Morphogenesis.

Tissue morphogenesis arises from controlled cell deformations in response to cellular contractility. During Drosophila gastrulation, apical activation of the actomyosin networks drives apical constriction in the invaginating mesoderm and cell-cell intercalation in the extending ectoderm. Myosin II (MyoII) is activated by cell-surface G protein-coupled receptors (GPCRs), such as Smog and Mist, that activate G proteins, the small GTPase Rho1, and the kinase Rok. Quantitative control over GPCR and Rho1 activation underlies differences in deformation of mesoderm and ectoderm cells. We show that GPCR Smog activity is concentrated on two different apical plasma membrane compartments, i.e., the surface and plasma membrane invaginations. Using fluorescence correlation spectroscopy, we probe the surface of the plasma membrane, and we show that Smog homo-clusters in response to its activating ligand Fog. Endocytosis of Smog is regulated by the kinase Gprk2 and ß-arrestin-2 that clears active Smog from the plasma membrane. When Fog concentration is high or endocytosis is low, Smog rearranges in homo-clusters and accumulates in plasma membrane invaginations that are hubs for Rho1 activation. Lastly, we find higher Smog homo-cluster concentration and numerous apical plasma membrane invaginations in the mesoderm compared to the ectoderm, indicative of reduced endocytosis. We identify that dynamic partitioning of active Smog at the surface of the plasma membrane or plasma membrane invaginations has a direct impact on Rho1 signaling. Plasma membrane invaginations accumulate high Rho1-guanosine triphosphate (GTP) suggesting they form signaling centers. Thus, Fog concentration and Smog endocytosis form coupled regulatory processes that regulate differential Rho1 and MyoII activation in the Drosophila embryo.

Modular activation of Rho1 by GPCR signalling imparts polarized myosin II activation during morphogenesis.

Polarized cell shape changes during tissue morphogenesis arise by controlling the subcellular distribution of myosin II. For instance, during Drosophila melanogaster gastrulation, apical constriction and cell intercalation are mediated by medial-apical myosin II pulses that power deformations, and polarized accumulation of myosin II that stabilizes these deformations. It remains unclear how tissue-specific factors control different patterns of myosin II activation and the ratchet-like myosin II dynamics. Here we report the function of a common pathway comprising the heterotrimeric G proteins Gα12/13, Gß13F and Gγ1 in activating and polarizing myosin II during Drosophila gastrulation. Gα12/13 and the Gß13F/γ1 complex constitute distinct signalling modules, which regulate myosin II dynamics medial-apically and/or junctionally in a tissue-dependent manner. We identify a ubiquitously expressed GPCR called Smog required for cell intercalation and apical constriction. Smog functions with other GPCRs to quantitatively control G proteins, resulting in stepwise activation of myosin II and irreversible cell shape changes. We propose that GPCR and G proteins constitute a general pathway for controlling actomyosin contractility in epithelia and that the activity of this pathway is polarized by tissue-specific regulators.