DHATUROOPI SHUKRA AND BEEJAROOPI SHUKRA: A CRITICAL REVIEW

Shukra is studied in Ayurveda both as a dhatu and beeja. As a mammalian human body comprises both somatic and gonadal cells. Somatic cells help for growth and regeneration through mitosis. Meiotic cell division causes equal contribution for the inheritance from maternal and paternal sides. Beejartham (reproduction) is the supreme function attributed to Shukra. Reproduction refers to the formation of new cells for tissue growth, repair/replacement (sukshmavayavantarotpatti), or the production of a new individual (shareerantarotpatti). Regenerative capacity is distributed unequally among species, individuals, and tissues. The affliction of shukrastana by kusthadosha (skin disease) causes a failure in regeneration. The affliction of parents' shukra and artava (gametes) by kusthadosha (skin disease) inherits to the next generation. Vrushan (testis) and medru (penis) are the moola of the shukravahavaha srotus, which is meant to fertilise the ovum (beejarupishukra). Majja (bone marrow) and stana (breasts) are the moola of the shukravaha srotus of the one pervading the entire body (dhaturupishukra).

Hepatocyte generation in liver homeostasis, repair, and regeneration

The liver has remarkable capability to regenerate, employing mechanism to ensure the stable liver-to-bodyweight ratio for body homeostasis. The source of this regenerative capacity has received great attention over the past decade yet still remained controversial currently. Deciphering the sources for hepatocytes provides the basis for understanding tissue regeneration and repair, and also illustrates new potential therapeutic targets for treating liver diseases. In this review, we describe recent advances in genetic lineage tracing studies over liver stem cells, hepatocyte proliferation, and cell lineage conversions or cellular reprogramming. This review will also evaluate the technical strengths and limitations of methods used for studies on hepatocyte generation and cell fate plasticity in liver homeostasis, repair and regeneration.

Signaling modality within gp130 receptor enhances tissue regeneration

Adult mammals are incapable of multi-tissue regeneration and augmentation of this potential may drastically shift current therapeutic paradigms. Here, we found that a common co-receptor of IL-6 cytokines, glycoprotein 130 (gp130), serves as a major nexus integrating various context-specific signaling inputs to either promote regenerative outcomes or aggravate disease progression. Via genetic and pharmacological experiments in vitro and in vivo, we demonstrated that a signaling tyrosine 814 (Y814) within gp130 serves as a major cellular stress sensor. Mice with constitutively inactivated Y814 (F814) exhibit regenerative, not reparative, responses after wounding in skin and anti-degenerative responses in the synovial joint. In addition, pharmacological inhibition of gp130 Y814 results in regeneration of multiple tissues in several species as well as disease modification in animal models of osteoarthritis. Our study characterizes a novel molecular mechanism that, if selectively manipulated, enhances the intrinsic regenerative capacity while preventing pathological outcomes in injury and disease.

Damage to Olfactory Organs of Adult Zebrafish Induced by Diesel Particulate Matter

Particulate matter (PM) is an environmental hazard that is associated with various human health risks. The olfactory system is directly exposed to PM; therefore, the influence of PM exposure on olfactory function must be investigated. In this study, we propose a zebrafish olfactory model to evaluate the effects of exposure to diesel particulate matter (DPM), which was labeled Korean diesel particulate matter (KDP20). KDP20 comprises heavy metals and polycyclic aromatic hydrocarbons (PAHs). KDP20 exposed olfactory organs exhibited reduced cilia and damaged epithelium. Olfactory dysfunction was confirmed using an odor-mediated behavior test. Furthermore, the olfactory damage was analyzed using Alcian blue and anti-calretinin staining. KDP20 exposed olfactory organs exhibited histological damages, such as increased goblet cells, decreased cell density, and calretinin level. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that PAHs exposure related genes (AHR2 and CYP1A) were upregulated. Reactive oxidation stress (ROS) (CAT) and inflammation (IL-1B) related genes were upregulated. Furthermore, olfactory sensory neuron (OSN) related genes (OMP and S100) were downregulated. In conclusion, KDP20 exposure induced dysfunction of the olfactory system. Additionally, the zebrafish olfactory system exhibited a regenerative capacity with recovery conditions. Thus, this model may be used in future investigating PM-related diseases.

In vitro regeneration of soybean (a review)

This is an overview of contemporary published works dedicated to the ability of soybean plants to regenerate in vitro and the techniques to achieve high regeneration rates, which is a necessary condition for the inclusion of soybean genotypes in genome editing programs. The main factors that determine the regenerative capacity of explants from various soybean accessions are considered. The greatest effect on the efficiency of regeneration is exerted by the conditions of in vitro culture initiation, type of explant, composition of the nutrient medium, shelf life of seeds, and genotypic characteristics of soybean accessions.

Extracellular vesicles: a promising cell-free therapy for cartilage repair

Few effective therapies for cartilage repair have been found as cartilage has a low regenerative capacity. Extracellular vesicles (EVs), including exosomes, are produced by cells and contain bioactive components such as nucleic acids, proteins, lipids and other metabolites that have potential for treating cartilage injuries. Challenges like the difficulty in standardizing targeted therapy have prevented EVs from being used frequently as a treatment option. In this review we present current studies, mechanisms and delivery strategies of EVs. Additionally, we describe the challenges and future directions of EVs as therapeutic agents for cartilage repair.

Immune Surveillance of Senescent Cells

Cellular senescence involves a stable cell cycle arrest and a secretory program that modulates the tissue environment. In cancer, senescence acts as a potent barrier to tumorigenesis and, though many cancers evade senescence during the course of tumor evolution, ionizing radiation and conventional chemotherapy can, to varying degrees, induce senescence in tumor cells leading to potent anticancer effects. Conversely, the aberrant accumulation of senescent cells can reduce regenerative capacity and lead to tissue decline, contributing to tissue pathologies associated with age or the debilitating side-effects of cancer therapy. Our laboratory studies mechanisms of cellular senescence with the ultimate goal of developing strategies to modulate senescence for therapeutic benefit. We have focused on how senescent cells trigger immune surveillance to facilitate their own elimination or, when that fails, how synthetic immune cells (i.e. CAR T cells) can be directed to eliminate senescent cells. Recent advances in understanding senescent cell surveillance by the immune system will be discussed.

The Impact of Short-Term Dietary Restriction on Stem Cell Function

Stem cells play a critical role in the maintenance of tissue function and their proliferative/regenerative capacity is essential to this role. Because stem cells persist over the lifespan of an animal, they are susceptible to gradual accumulation of age-associated damage, resulting in the loss of regenerative function that can impair organ function. Understanding the mechanism(s) that regulates stem cell function is essential for retarding the aging process, and stem cells are attractive targets for aging interventions. Dietary restriction (DR), the most robust anti-aging intervention to-date, has been shown to enhance the activity and integrity of stem cells in a variety of tissues (e.g., muscle, bone marrow, and intestine), and it is believed that effect of DR on stem cells plays an important role in the anti-aging action of DR. For example, DR has been shown to preserve and increase the number of intestinal stem cells (ISCs) and enhance their regenerative capacity in young animals. Data from my lab shows that ISCs from old mice have limited proliferation activity and form few if any organoids in vitro (a surrogate for a fully functional crypt) and that ISCs isolated from old mice on life-long DR show an improved ability to form organoids. While it is well accepted that life-long DR increases lifespan and has anti-aging effects an important aspect of DR that has been largely overlooked is that DR implemented only for a short time early in life can increase lifespan of rodents even when rodents are fed ad libitum the remainder of their life. In line with this, we recently found that ISCs from old mice fed DR for only a short-period resulted in a dramatic increase in ability of the ISCs to form organoids. This is the first evidence that short-term DR administrated late in life can rescue the loss in ISC function that occurs with age.

Thyroid hormone-dependent regulation of metabolism and heart regeneration

While adult zebrafish and newborn mice possess a robust capacity to regenerate their hearts, this ability is generally lost in adult mammals. The logic behind the diversity of cardiac regenerative capacity across the animal kingdom is not well understood. We have recently reported that animal metabolism is inversely correlated to the abundance of mononucleated diploid cardiomyocytes in the heart, which retain proliferative and regenerative potential. Thyroid hormones are classical regulators of animal metabolism, mitochondrial function, and thermogenesis and a growing body of scientific evidence demonstrates that these hormonal regulators also have direct effects on cardiomyocyte proliferation and maturation. We propose that thyroid hormones dually control animal metabolism and cardiac regenerative potential through distinct mechanisms, which may represent an evolutionary tradeoff for the acquisition of endothermy and loss of heart regenerative capacity. In this review, we describe the effects of thyroid hormones on animal metabolism and cardiomyocyte regeneration, and highlight recent reports linking the loss of mammalian cardiac regenerative capacity to metabolic shifts occurring after birth.