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Oligodendrocyte precursor cell differentiation into myelinating oligodendrocytes is critical for remyelination in the central nervous system after injury. In this issue of Neuron, Niu et al. (2021) detail a novel role for ring finger protein Rnf43, which is expressed in response to injury and is essential to promote remyelination in vivo.

Axon regeneration is orchestrated by many genes that are differentially expressed in response to injury. Through a comparative analysis of gene expression profiling, injury-responsive genes that are potential targets for understanding the mechanisms underlying regeneration have been revealed. As the efficiency of axon regeneration in both the peripheral and central nervous systems can be manipulated, we suggest that identifying regeneration-associated genes is a promising approach for developing therapeutic applications in vivo. Here, we review the possible roles of stem cell marker- or stemness-related genes in axon regeneration to gain a better understanding of the regeneration mechanism and to identify targets that can enhance regenerative capacity., Nerve cells: activating genetic switches to repair injury Understanding which genes are switched on/off in nerve cells in response to injury may help develop new treatments to repair nerves. Nerve cells can be cued to regenerate in both the central (brain and spinal cord) and peripheral nervous systems. Studying patterns of post-injury gene activation may allow therapeutic boosting of injury-responsive genes to cue nerve regrowth. Jinyoung Lee and Yongcheol Cho at Korea University, Seoul, South Korea have reviewed those genes identified as markers of stem cells (cells with high regenerative capacity) that are differentially regulated in nerve cells. They present several promising target genes for further study, noting that little is known of the mechanisms underlying regeneration or the interacting genetic pathways. These results point the way to identifying genetic targets to improve treatment for nerve damage.

Astrocytes are dynamic cells residing in the central nervous system exhibiting many diverse functions. Astrocytes quickly change and present unique phenotypes in response to injury or disease. Here, we briefly summarize recent information regarding astrocyte morphology and function and provide brief insight into their phenotypic changes following injury or disease. We also present the utility of in vitro astrocyte cultures and present recent advances in biomaterial development that enable better recapitulation of their in vivo behavior and morphology.

To facilitate rational experimental design and fulfill the NIH requirement of including sex as a biologic variable, we examined the influences of genetic background and sex on responses to intervertebral disc (IVD) injury in the mouse tail. The goal of this study was to compare gene expression and histologic changes in response to a tail IVD injury (needle puncture) in male and female mice on the DBA and C57BL/6 (B6) backgrounds. We hypothesized that extracellular matrix gene expression in response to IVD injury differs between mice of different genetic backgrounds and sex. Consistent changes were detected in gene expression and histologic features after IVD injury in mice on both genetic backgrounds and sexes. In particular, expression of col1a1 and adam8 was higher in the injured IVD of DBA mice than B6 mice. Conversely, col2a1 expression was higher in B6 mice than DBA mice. Sex-associated differences were significant only in B6 mice, in which col2a1 expression was greater in male mice than in female. Histologic differences in response to injury were not apparent between DBA and B6 mice or between males and females. In conclusion, mouse tail IVD showed sex- and strain-related changes in gene expression and histology after needle puncture. The magnitude of change in gene expression differed with regard to genetic background and, to a lesser degree, sex.

Plants display extraordinary ability to revive tissues and organs lost or damaged in injury. This is evident from the root tip restoration and classical experiments in stem demonstrating re-establishment of vascular continuity. While recent studies have begun to unravel the mechanistic understanding of tissue restoration in response to injury in underground plant organs, the molecular mechanisms of the same in aerial organs remain to be ventured deeper. Here, we discuss the possibility of unearthing the regulatory mechanism that can confer universal regeneration potential to plant body and further provide a comprehensive understanding of how tissue and organ regeneration gets triggered in response to mechanical injury and later gets terminated after re-patterning and regaining the appropriate size.

Single cell biology has the potential to elucidate many critical biological processes and diseases, from development and regeneration to cancer. Single cell analyses are uncovering the molecular diversity of cells, revealing a clearer picture of the variation among and between different cell types. New techniques are beginning to unravel how differences in cell state-transcriptional, epigenetic, and other characteristics-can lead to different cell fates among genetically identical cells, which underlies complex processes such as embryonic development, drug resistance, response to injury, and cellular reprogramming. Single cell technologies also pose significant challenges relating to processing and analyzing vast amounts of data collected. To realize the potential of single cell technologies, new computational approaches are needed. On March 17-19, 2021, experts in single cell biology met virtually for the Keystone eSymposium "Single Cell Biology" to discuss advances both in single cell applications and technologies.

Vascular remodeling is a prominent feature of pulmonary hypertension. This process involves increased muscularization of already muscularized vessels as well as neo-muscularization of non-muscularized vessels. The cell-of-origin of the newly formed vascular smooth muscle cells has been a subject of intense debate in recent years. Identifying these cells may have important clinical implications since it opens the door for attempts to therapeutically target the progenitor cells and/or reverse the differentiation of their progeny. In this context, the dominant model is that these cells derive from pre-existing smooth muscle cells that are activated in response to injury. In this mini review, we present the evidence that is in favor of this model and, at the same time, highlight other studies indicating that there are alternative cellular sources of vascular smooth muscle cells in pulmonary vascular remodeling.

Understanding the basic properties of how axons respond to injury in the mammalian central nervous system (CNS) is of fundamental value for developing strategies to promote neural repair. Axons possess complex morphologies with stereotypical branching patterns. However, current knowledge of the axonal response to injury gives little consideration to axonal branches, nor do strategies to promote axon regeneration. This article reviews evidence from in vivo spinal cord imaging that axonal branches markedly impact the degenerative and regenerative responses to injury. At a major bifurcation point, depending on whether one or both axonal branches are injured, neurons may choose either a more self-preservative response or a more dynamic response. The stabilizing effect of the spared branch may underlie a well-known divergence in neuronal responses to injury, and illustrates an example where in vivo spinal cord imaging reveals insights that are difficult to elucidate with conventional histological methods.

Schwann cell precursors (SCPs) are a transient population in the embryo, closely associated with nerves along which they migrate into the periphery of the body. Long considered to be progenitors that only form Schwann cells—the myelinating cells of nerves, current evidence suggests that SCPs have much broader developmental potential. Indeed, different cell marking techniques employed over the past 20 years have identified multiple novel SCP derivatives throughout the body. It is now clear that SCPs represent a multipotent progenitor population, which also display a level of plasticity in response to injury. Moreover, they originate from multiple origins in the embryo and may reflect several distinct subpopulations in terms of molecular identity and fate. Here we review SCP origins, derivatives and plasticity in development, growth and repair.

Complex tissue regeneration is extremely rare among adult mammals. An exception, however, is the superior tissue healing of multiple organs in spiny mice (Acomys). While Acomys species exhibit the remarkable ability to heal complex tissue with minimal scarring, little is known about their cardiac structure and response to cardiac injury. In this study, we first examined baseline Acomys cardiac anatomy and function in comparison with commonly used inbred and outbred laboratory Mus strains (C57BL6 and CFW). While our results demonstrated comparable cardiac anatomy and function between Acomys and Mus, Acomys exhibited a higher percentage of cardiomyocytes displaying distinct characteristics. In response to myocardial infarction, all animals experienced a comparable level of initial cardiac damage. However, Acomys demonstrated superior ischemic tolerance and cytoprotection in response to injury as evidenced by cardiac functional stabilization, higher survival rate, and smaller scar size 50 days after injury compared to the inbred and outbred mouse strains. This phenomenon correlated with enhanced endothelial cell proliferation, increased angiogenesis, and medium vessel maturation in the peri-infarct and infarct regions. Overall, these findings demonstrate augmented myocardial preservation in spiny mice post-MI and establish Acomys as a new adult mammalian model for cardiac research.

Microglia are tissue-resident macrophages implicated in central nervous system (CNS) development, homeostasis, and response to injury. Recent advances in transcriptomics, multiplex protein expression analysis, and experimental depletion of microglia have cemented their importance. However, it is still unclear which models are best suited to investigate microglia and explore their function in human disease. Here, we discuss issues regarding off-targeting during experimental manipulation, and differences and similarities between human and rodent microglia. With new developments in transgenic lines and human–rodent chimeras, we anticipate that in coming years, a clearer picture of microglia function in health and disease will emerge.

Central nervous system damage in mammals leads to neuronal cell death, axonal degeneration, and formation of a glial scar resulting in functional and behavioral defects. Other vertebrates, like fish and salamanders, have retained the ability to functionally regenerate after central nervous system injury. To date research from many research organisms has led to a more concise understanding of the response of local neural cells to injury. However, it has become clear that non-neural cells of the immune system play an important role in determining the tissue response to injury. In this review we briefly consider the mammalian response to injury compared to organisms with the natural ability to regenerate. We then discuss similarities and differences in how cells of the innate and adaptive immune system respond and contribute to tissue repair in various species.

The potential rapid advance of regenerative medicine was obstructed by findings that stimulation of human body regeneration is a much tougher mission than expected after the first cultures of stem and progenitor cells were established. In this mini review, we focus on the ambiguous role of growth factors in regeneration, discuss their evolutionary importance, and highlight them as the "cure and the cause" for successful or failed attempts to drive human body regeneration. We draw the reader's attention to evolutionary changes that occurred in growth factors and their receptor tyrosine kinases (RTKs) and how they established and shaped response to injury in metazoans. Discussing the well-known pleiotropy of growth factors, we propose an evolutionary rationale for their functioning in this specific way and focus on growth factors and RTKs as an amazing system that defines the multicellular nature of animals and highlight their participation in regeneration. We pinpoint potential bottlenecks in their application for human tissue regeneration and show their role in fibrosis/regeneration balance. This communication invites the reader to re-evaluate the functions of growth factors as keepers of natively existing communications between elements of tissue, which makes them a fundamental component of a successful regenerative strategy. Finally, we draw attention to the epigenetic landscape that may facilitate or block regeneration and give a brief insight into how it may define the outcome of injury.

Extracellular matrix (ECM) is the foundation on which all cells and organs converge to orchestrate normal physiological functions. In the setting of pathology, the ECM is modified to incorporate additional roles, with modifications including turnover of existing ECM and deposition of new ECM. The fibroblast is center stage in coordinating both normal tissue homeostasis and response to disease. Understanding how fibroblasts work under normal conditions and are activated in response to injury or stress will provide mechanistic insight that triggers discovery of new therapeutic treatments for a wide range of disease. We highlight here fibroblast roles in the cancer, lung, and heart as example systems where fibroblasts are major contributors to homeostasis and pathology.

Background: Inflammation is a normal process in response to injury, but causes problems for the patient, including the appearance of pain, swelling, or fever. Anti-inflammatory agents generally used for those conditions, have several side effects to patients. Purpose: The objective of this research was to find alternative anti-inflammatory agents, especially from natural sources. Eleutherine bulbosa (Mill.) Urb. knew as “Bawang Dayak” belong to family Iridaceae is one of the natural sources for anti-inflammatory agents. This plant is known as traditional medicine in East Kalimantan and used as material in this research. Method: The experimental method of anti-inflammatory measurement using membrane stabilization activity for E. Bulbosa ethanol bulbs extracts. Result: The results showed that significant differences of EC 50 (p < 0.05) were achieved between indomethacin (26.39 ± 2.91) as the positive control with E. Bulbosa (52.87 ± 2.29). EC 50 of E. bulbosa showed the potential anti-inflammatory activities with similar effectiveness to half indomethacin concentration. Conclusion: It could be concluded that E. bulbosa could be further developed as a new natural source of the anti-inflammatory agents.

SummaryCortical maps often undergo plastic changes during learning or in response to injury. In sensory areas, these changes are thought to be triggered by alterations in the pattern of converging inputs and a functional reassignment of the deprived cortical region. In the motor cortex, training on a task that engages distal effectors was shown to increase their cortical representation (as measured by response to intracortical microstimulation). However, this expansion could be a specific outcome of using a demanding dexterous task. We addressed this question by measuring the long-term changes in cortical maps of monkeys that were sequentially trained on two different tasks involving either proximal or distal joints. We found that motor cortical remodeling in adult monkeys was symmetric such that both distal and proximal movements can comparably alter motor maps in a fully reversible manner according to task demands. Further, we found that the change in mapping often included a switch between remote joints (e.g., a finger site switched to a shoulder site) and reflected a usage-consistent reorganization of the map rather than the local expansion of one representation into nearby sites. Finally, although cortical maps were considerably affected by the performed task, motor cortical neurons throughout the motor cortex were equally likely to fire in a task-related manner independent of the task and/or the recording site. These results may imply that in the motor system, enhanced motor efficiency is achieved through a dynamical allocation of larger cortical areas and not by specific recruitment of task-relevant cells.

The extracellular matrix is an active participant, modulator and mediator of the cell, tissue, organ and organismal response to injury. Recent research has highlighted the role of hyaluronan, an abundant glycosaminoglycan constituent of the extracellular matrix, in many fundamental biological processes underpinning homeostasis and disease development. From this basis, emerging studies have demonstrated the therapeutic potential of strategies which target hyaluronan synthesis, biology and signaling, with significant promise as therapeutics for a variety of inflammatory and immune diseases. This review summarizes the state of the art in this field and discusses challenges and opportunities in what could emerge as a new class of therapeutic agents, that we term “matrix biologics”.

The rapid advancement of additive manufacturing technologies and their extension into biological systems have led to the emergence of a new category of cell-based models, namely bioprinted...

Monocytes and their progeny, macrophages (MPhs), play the leading role in the innate immunity and populate different tissues maintaining homeostasis. In addition, these cells are involved in the response to injury when they accumulate in significant numbers at inflammatory sites. As well as macrophages, multipotent mesenchymal stromal cells (MSCs) are a critical component of both physiological and emerging regenerative microenvironment. Reciprocal effects of resident stromal and recruited blood-borne cells orchestrate cellular reactions in the tissues. Hypoxia, a significant reduction in the O2 concentration, is a characteristic feature of the compromised microenvironment. The present review analyzes the current concepts of the role of MSC interaction with MPhs in physiological and reparative tissue remodeling, modulation of MSC and MPh functions under acute hypoxic stress and discusses how oxygen deprivation can affect the outcome of MSC–MPh interplay.

Paramita S, Kosala K, Dzulkifli D, Saputri DI, Wijayanti E. 2017. Anti-inflammatory activities of ethnomedicinal plants from Dayak Abai in North Kalimantan, Indonesia. Biodiversitas 18: 1556-1561. Inflammation is a normal process in the human body as a response to injury from the healing process. Meanwhile, chronic inflammation will cause new health problems to patients. Antiinflammatory drugs generally used for those conditions, have several side effects to patients. The objective of this research was to find alternative anti-inflammatory drugs, especially from natural sources. Three medicinal plants recorded from Dayak Abai in North Kalimantan, Indonesia for health problems caused by the inflammation process i.e. Amomum xanthophlebium Baker, Clerodendrum buchananii (Roxb.) Walp., and Donax canniformis (G.Forst.) K.Schum. were used as material in this research. The experimental method using carrageenan-induced rat paw edema was used followed by the resulting measurement using plethysmometer. The results showed that significant differences of AUC (area under the curve) with p = 0.001 (p < 0.05) were achieved between negative control, positive control, and treatment group with plant medicinal extracts. AUC of leaves ethanol extract of C. buchananii showed the strongest antiinflammatory activities. It could be concluded that the medicinal plants recorded from ethnomedicinal data from Dayak Abai in North Kalimantan, have anti-inflammatory activities, with C. buchananii as the most potential ones which could be further developed as a new source of the anti-inflammatory drug.

Lay Summary Here, we show that one species of leaf-footed bug can self-amputate an injured limb to reduce the cost of injury. Other benefits of self-amputation include escaping predation and escaping entrapment. By identifying different benefits of this behavior, we stand to gain a more comprehensive understanding of how such an extreme trait evolves., Autotomy, self-induced limb loss, is an extreme trait observed throughout the animal kingdom; lizards drop their tails, crickets release their legs, and crabs drop their claws. These repeated evolutionary origins suggest that autotomy is adaptive. Yet, we do not have a firm understanding of the selective pressures that promote and maintain this extreme trait. Although multiple adaptive hypotheses exist, research has generally focused on autotomy’s adaptive value as a form of predator escape. However, autotomy could also be selected to reduce the cost of an injured limb, which we investigate here. Previously, this alternative hypothesis has been challenging to directly test because when an injury occurs on an autotomizable limb, that limb is almost always dropped (i.e., autotomy is behaviorally fixed within populations). Recently, however, we have identified a species, Narnia femorata (Insecta: Hemiptera: Coreidae), where some individuals autotomize limbs in response to injury, but some do not. This natural variation allowed us to investigate both the survival costs of retaining an injured limb and the benefits of autotomizing it. In this study, we find a positive association between autotomizing injured limbs and survival, thereby quantifying a new and likely widespread benefit of autotomy—reducing the cost of injury.

The cellular and mechanistic bases underlying endothelial regeneration of adult large vessels have proven challenging to study. Using a reproducible in vivo aortic endothelial injury model, we characterized cellular dynamics underlying the regenerative process through a combination of multi-color lineage tracing, parabiosis, and single-cell transcriptomics. We found that regeneration is a biphasic process driven by distinct populations arising from differentiated endothelial cells. The majority of cells immediately adjacent to the injury site re-enter the cell cycle during the initial damage response, with a second phase driven by a highly proliferative subpopulation. Endothelial regeneration requires activation of stress response genes including Atf3, and aged aortas compromised in their reparative capacity express less Atf3. Deletion of Atf3 reduced endothelial proliferation and compromised the regeneration. These findings provide important insights into cellular dynamics and mechanisms that drive responses to large vessel injury.

Currently, table olives, unlike oil olives, are harvested manually. Shortage of manpower and increasing labor costs are the main incentives to mechanizing the harvesting of table olives. One of the major limiting factors in adopting mechanical harvest of table olives is the injury to fruit during mechanical harvest, which lowers the quality of the final product. In this study, we used the Israeli germplasm collection of olive cultivars at the Volcani Institute to screen the sensitivity of many olive cultivars to browning in response to injury. The browning process after induced mechanical injury was characterized in 106 olive cultivars. The proportional area of brown coloring after injury, compared to the total fruit surface area, ranged from 0 to 83.61%. Fourteen cultivars were found to be resistant to browning and did not show any brown spot 3 h after application of pressure. Among them, there are some cultivars that can serve as table olives. The different response to mechanical damage shown by the cultivars could be mainly due to genetic differences. Mesocarp cells in the fruits of the sensitive cultivars were damaged and missing the cell wall as a result of the applied pressure. The cuticles of resistant cultivars were thicker compared to those of susceptible cultivars. Finally, we showed that the browning process is enzymatic. We suggest cuticle thickness as an indicator of table olive cultivars suitable for mechanical harvest. A shift to browning-resistant cultivars in place of the popular cultivars currently in use will enable the mechanical harvest of table olive without affecting fruit quality.

The nucleus houses and protects genomic DNA, which is surrounded by the nuclear envelope. Owing to its size and stiffness, the nucleus is often a barrier to migration through confined spaces. Neutrophils are terminally differentiated, short-lived cells that migrate through tissues in response to injury and infections. The neutrophil nucleus is soft, multilobular, and exhibits altered levels of key nuclear envelope proteins. These alterations result in a multifunctional organelle that serves as a signaling hub during migration and NETosis, a process by which neutrophils release decondensed chromatin decorated with granular enzymes that entrap pathogens. In this review, we present emerging evidence suggesting that a unique, ambiguous cell-cycle state is critical for NETosis and migration. Finally, we discuss how the mechanisms underlying migration and NETosis are evolutionarily conserved.

Background/Hypothesis Hedgehog (Hh) signaling not only plays a crucial role in embryonic development, but also controls gastric physiological events including epithelial cell differentiation, regen...

Zebrafish can regenerate their hearts. The role of the extracellular matrix in this process is largely unknown. We have analyzed the proteome in control hearts and at different times of regeneration. Decellularization of samples allowed for enrichment of extracellular matrix proteins, increasing their detection. The results reported dynamic changes in specific proteins associated with specific stages of the regenerative process. Biomechanical analysis by atomic force microscopy revealed concomitant changes in matrix stiffness during this process., Graphical Abstract Highlights We have developed a decellularization protocol for ECM protein enrichment. We have characterized the proteome of adult zebrafish heart ECM. We describe dynamic changes in heart ECM proteome during regeneration. We describe changes in heart ECM stiffness during regeneration., Adult zebrafish, in contrast to mammals, are able to regenerate their hearts in response to injury or experimental amputation. Our understanding of the cellular and molecular bases that underlie this process, although fragmentary, has increased significantly over the last years. However, the role of the extracellular matrix (ECM) during zebrafish heart regeneration has been comparatively rarely explored. Here, we set out to characterize the ECM protein composition in adult zebrafish hearts, and whether it changed during the regenerative response. For this purpose, we first established a decellularization protocol of adult zebrafish ventricles that significantly enriched the yield of ECM proteins. We then performed proteomic analyses of decellularized control hearts and at different times of regeneration. Our results show a dynamic change in ECM protein composition, most evident at the earliest (7 days postamputation) time point analyzed. Regeneration associated with sharp increases in specific ECM proteins, and with an overall decrease in collagens and cytoskeletal proteins. We finally tested by atomic force microscopy that the changes in ECM composition translated to decreased ECM stiffness. Our cumulative results identify changes in the protein composition and mechanical properties of the zebrafish heart ECM during regeneration.

Mammalian biologic scaffolds composed of extracellular matrix (ECM) contain countless structural and functional moieties that have been shown to be necessary for tissue development, homeostasis, and response to injury. Biologic scaffold materials are employed in clinical medicine and their use will likely expand as regenerative medicine strategies evolve. This chapter discusses the generation and use of biologic scaffold materials for regenerative medicine applications with a focus on ECM scaffolds. The biologic properties and known functions of the individual components of the ECM, the generation of three-dimensional whole-organ scaffolds, and the federal regulation of biologic scaffolds are also discussed.

The limb musculoskeletal system provides a primary means for locomotion, manipulation of objects and protection for most vertebrate organisms. Intricate integration of the bone, tendon and muscle tissues are required for function. These three tissues arise largely independent of one another, but the connections formed during later development are maintained throughout life and are re-established following injury. Each of these tissues also have mesenchymal stem/progenitor cells that function in maintenance and repair. Here in, we will review the major events in the development of limb skeleton, tendon, and muscle tissues, their response to injury, and discuss current knowledge regarding resident progenitor/stem cells within each tissue that participate in development, repair, and regeneration in vivo.

Third-hand smoke (THS) is a recently discovered environmental health hazard that results from accumulation and aging of second-hand smoke (SHS) toxins on surfaces of environments where smoking has occurred. Our objective was to determine whether there is a dose-dependent effect of THS exposure on biological markers of harm (BMH) using an in vivo exposure system that mimics exposure of humans to THS. THS exposure generated from as low as the 10 cigarettes-smoking regimen, resulted in increased circulating inflammatory cytokines, tumor necrosis factor alpha, interleukin 1 alpha, and granulocyte macrophage colony-stimulating factor. We also found that there was an increase in adrenocorticotropic hormone and superoxide dismutase and a decrease in ATP levels in liver tissue. Many of the altered BMH that are related to oxidative stress and decrease in ATP levels, suggest mitochondrial dysfunction. THS exposure generated from the 20 and 40 cigarettes-smoking regimen resulted in further damage. Our studies are important because virtually nothing is known about the physiological damage caused by different levels of THS exposure. These studies can also serve to educate the public on the dangers of THS and the BMH we identified can potentially be used in the clinic, once verified in exposed humans.

Explanations for patterns of healed trauma in Neanderthals have been a matter of debate for several decades. Despite widespread evidence for recovery from injuries or survival despite impairments, apparent evidence for healthcare is given limited attention. Moreover, interpretations of Neanderthal’s approach to injury and suffering sometimes assume a calculated or indifferent attitude to others. Here we review evidence for Neanderthal healthcare, drawing on a bioarchaeology of care approach and relating healthcare to other realms of Neanderthal social life. We argue that Neanderthal medical treatment and healthcare was widespread and part of a social context of strong pro-social bonds which was not distinctively different from healthcare seen in later contexts. We suggest that the time has come to accept Neanderthal healthcare as a compassionate and knowledgeable response to injury and illness, and to turn to other questions, such as cultural variation or the wider significance of healthcare in an evolutionary context.

Blood vessels significantly remodel in response to injury and pathologic conditions, although the contribution of stem cells to this process is unclear. Now in Cell Stem Cell, Kramann et al. (2016) show that Gli1+ perivascular cells in the outermost vessel layer are progenitors that substantially contribute to pathologic vessel remodeling.

Inflammation is a normal process in the human body as a response to injury from the healing process. Meanwhile, chronic inflammation will cause new health problems to patients. Anti-inflammatory agents generally used for those conditions, have several side effects to patients. The objective of this research was to find alternative anti-inflammatory agents, especially from natural sources. Vernonia amygdalina Delile knew locally as “Daun Bismillah” belong to family Apiaceae is one of those potential natural sources for alternative anti-inflammatory agents. This plant is known as traditional medicine and used as material in this research. The experimental method of in vitro anti-inflammatory measurement using membrane stabilization activity for ethanol extracts of V. amygdalina leaves. The results showed that significant differences of EC50 (p

Bone marrow-derived monocytes are important constituents of the innate immune system. In both humans and rodents, monocyte subsets have been identified that play distinct roles during homeostatic and inflammatory states. Notable functional differences are observed in monocyte subsets in response to signals generated in the local microenvironment demonstrating the plastic nature of these cells. Herein, we review recent findings on the phenotype of monocytes subsets, their functions, and their differentiation into macrophages and dendritic cells in response to injury and infection.

The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans.

Almost every disorder of the CNS is said to have an inflammatory component, but the precise nature of inflammation in the CNS is often imprecisely defined, and the role of CNS-resident cells is uncertain compared with that of cells that invade the tissue from the systemic immune compartment. To understand inflammation in the CNS, the term must be better defined, and the response of tissue to disturbances in homoeostasis (eg, neurodegenerative processes) should be distinguished from disorders in which aberrant immune responses lead to CNS dysfunction and tissue destruction (eg, autoimmunity). Whether the inflammatory tissue response to injury is reparative or degenerative seems to be dependent on context and timing, as are the windows of opportunity for therapeutic intervention in inflammatory CNS diseases.

Despite approaches in regenerative medicine using stem cells, bio-engineered scaffolds, and targeted drug delivery to enhance human tissue repair, clinicians remain unable to regenerate large-scale, multi-tissue defects in situ. The study of regenerative biology using mammalian models of complex tissue regeneration offers an opportunity to discover key factors that stimulate a regenerative rather than fibrotic response to injury. For example, although primates and rodents can regenerate their distal digit tips, they heal more proximal amputations with scar tissue. Rabbits and African spiny mice re-grow tissue to fill large musculoskeletal defects through their ear pinna, while other mammals fail to regenerate identical defects and instead heal ear holes through fibrotic repair. This Review explores the utility of these comparative healing models using the spiny mouse ear pinna and the mouse digit tip to consider how mechanistic insight into reparative regeneration might serve to advance regenerative medicine. Specifically, we consider how inflammation and immunity, extracellular matrix composition, and controlled cell proliferation intersect to establish a pro-regenerative microenvironment in response to injuries. Understanding how some mammals naturally regenerate complex tissue can provide a blueprint for how we might manipulate the injury microenvironment to enhance regenerative abilities in humans.

Pericytes are essential for vessel maturation and endothelial barrier function. Long noncoding RNAs regulate many cellular functions, but their role in pericyte biology remains unexplored.Here, we investigate the effect of hypoxia-induced endoplasmic reticulum stress regulating long noncoding RNAs (HypERlnc, also known as ENSG00000262454) on pericyte function in vitro and its regulation in human heart failure and idiopathic pulmonary arterial hypertension.RNA sequencing in human primary pericytes identified hypoxia-regulated long noncoding RNAs, including HypERlnc. Silencing of HypERlnc decreased cell viability and proliferation and resulted in pericyte dedifferentiation, which went along with increased endothelial permeability in cocultures consisting of human primary pericyte and human coronary microvascular endothelial cells. Consistently, Cas9-based transcriptional activation of HypERlnc was associated with increased expression of pericyte marker genes. Moreover, HypERlnc knockdown reduced endothelial-pericyte recruitment in Matrigel assays (Here, we show that HypERlnc regulates human pericyte function and the endoplasmic reticulum stress response. In addition, RNA sequencing analyses in conjunction with reduced expression of HypERlnc in heart failure and correlation with pericyte markers in idiopathic pulmonary arterial hypertension indicate a role of HypERlnc in human cardiopulmonary disease.

Traumatic spinal cord injury is characterized by an initial cell loss that is followed by a concerted cellular response in an attempt to restore the damaged tissue. Nevertheless, little is known about the signaling mechanisms governing the cellular response to injury. Here, we have established an adult ex vivo system that exhibits multiple hallmarks of spinal cord injury and allows the study of complex processes that are difficult to address using animal models. We have characterized the ependymal cell response to injury in this model system and found that ependymal cells can become activated, proliferate, migrate out of the central canal lining and differentiate in a manner resembling the in vivo situation. Moreover, we show that these cells respond to external adenosine triphosphate and exhibit spontaneous Ca2+ activity, processes that may play a significant role in the regulation of their response to spinal cord injury. This model provides an attractive tool to deepen our understanding of the ependymal cell response after spinal cord injury, which may contribute to the development of new treatment options for spinal cord injury.

Although the premature abscission of leaves damaged by herbivores has been discovered decades ago, the reduction in leaf life span caused by herbivory remains poorly documented, and the sources of variation in the magnitude of this effect have only rarely been studied. We aimed at exploring the effects of several herbivore species (at their background densities) and simulated herbivory on the leaf life span of downy birch, Betula pubescens Ehrh. Leaves damaged by herbivores abscised on average 12.6 days earlier and punched leaves 3.5 days earlier than the intact leaves of the control shoots. Different herbivores reduced the life span of the birch leaves from 0% to 27% depending on the intensity and timing of the damage but not on the insect feeding guild. The reduction in leaf life span was greater when the damage was imposed on expanding and growing leaves compared with mature leaves. However, the effect of herbivore species remained significant after accounting for intensity and timing of damage. This fact, together with greater reduction in leaf life span due to natural herbivory compared with mechanical damage, indicates that premature abscission in response to injury is considerably enhanced by insect-specific elicitors.

This chapter is focused on the response to injury at the cellular level, but the student must remember that an injured cell is affected not only by its direct injury but also by neighboring and distant cells, stroma, and vasculature, and that the injured cell in turn affects cells and tissues around it (and at distant sites). In subsequent chapters we will see how blood flow, the inflammatory response, the immune response, and other factors come into play and realize that the whole body, not just one or a few cells, responds to injury.

Understanding the role of factors that regulate intestinal epithelial homeostasis and response to injury and regeneration is important. The current literature describes several different methodological approaches to obtain images of intestinal tissues for data validation. In this paper, we delineate a common protocol relating to the derivation and processing of mouse intestinal tissues. Proper fixation of intestinal tissues and Swiss-roll techniques that enhance intestinal epithelial morphology are discussed. Postresection processing and reorientation of embedded intestinal tissues are critical in obtaining paraffin-embedded blocks that display intact intestinal structural features after sectioning. The Swiss-rolling technique helps in histological assessment of the complete intestinal or colonic sections examined. An ability to differentiate intestinal structural features can be vital in quantitative measurements of intestinal inflammation and tumorigenesis along the entire length. Finally, paraffin-embedded sections are ideal for robust processing using both immunohistochemical and immunofluorescent detection methods. Nonfluorescent immunohistochemical sections provide a vibrant image of the tissue detailing different cellular structural features but do not provide flexibility for intracellular co-localization experiments. Multiple fluorescent channels can be appropriately utilized with immunofluorescent detection for co-localization experiments, lending support to mechanistic studies.

Astrocytes are the most abundant cell type in the adult central nervous system (CNS), and their functional diversity in response to injury is now being appreciated. Astrocytes have long been considered the main player in the inhibition of CNS repair via the formation of the gliotic scar, but now it is accepted that astrocyte can play an important role in CNS repair and remyelination. Interest in the relationship between astrocytes and myelination focused initially on attempts to understand how the development of plaques of astroglial scar tissue in multiple sclerosis was related to the failure of these lesions to remyelinate. It is now considered that this is an end stage pathological response to injury, and that normally astrocytes play important roles in supporting the development and maintenance of CNS myelin. This review will focus on how this new understanding may be exploited to develop new strategies to enhance remyelination in multiple sclerosis and other diseases.

In this issue of Neuron, Napoli et al. (2012) demonstrate that elevated ERK/MAPK signaling in Schwann cells is a crucial trigger for Schwann cell dedifferentiation in vivo. Moreover, the authors show that dedifferentiated Schwann cells have the potential to coordinate much of the peripheral nerve response to injury.

Epithelial stem cells maintain the skin's epidermis and promote wound healing in response to injury. Scientists from two fields discuss implications of the discovery that these stem cells harbour a memory of previous injuries, which enables skin to respond rapidly to subsequent assaults. See Article p.475 In the skin, epithelial stem cells form a barrier against environmental damage. Shruti Naik et al. now show that after acute inflammation, epithelial stem cells retain a memory that hastens barrier restoration during subsequent tissue damage. However, the increased sensitivity to further insults may also increase tissue damage and susceptibility to other disorders such as autoimmune diseases and cancer.

During neonatal development, tendons undergo a well-orchestrated process whereby extensive structural and compositional changes occur in synchrony to produce a normal tissue. Conversely, during the repair response to injury, structural and compositional changes occur, but a mechanically inferior tendon is produced. As a result, developmental processes have been postulated as a potential paradigm through which improved adult tissue healing may occur. By examining injury at distinctly different stages of development, vital information can be obtained into the structure-function relationships in tendon. The mouse is an intriguing developmental model due to the availability of assays and genetically altered animals. However, it has not previously been used for mechanical analysis of healing tendon due to the small size and fragile nature of neonatal tendons. The objective of this study was to evaluate the differential healing response in tendon at two distinct stages of development through mechanical, compositional, and structural properties. To accomplish this, a new in vivo surgical model and mechanical analysis method for the neonatal mouse Achilles tendons were developed. We demonstrated that injury during early development has an accelerated healing response when compared to injury during late development. This accelerated healing model can be used in future mechanistic studies to elucidate the method for improved adult tendon healing.