Can pyrolysis handle biomedical wastes?: Assessing the potential of various biomedical waste treatment technologies in tackling pandemics.

Globally, COVID-19 has not only caused tremendous negative health, social and economic impacts, but it has also led to environmental issues such as a massive increase in biomedical waste. The biomedical waste (BMW) was generated from centralized (hospitals, clinics, and research facilities) and extended (quarantine camps, COVID-19 test camps, and quarantined homes) healthcare facilities. Many effects, such as the possibility of infection spread, unlawful dumping/disposal, and an increase in toxic emissions by common BMW treatment facilities, are conjectured because of the rise in waste generation. However, it is also an opportunity to critically analyze the current BMW treatment scenario and implement changes to make the system more economical and environmentally sustainable. In this review, the waste disposal guidelines of the BMW management infrastructure are critically analyzed for many functional parameters to bring out possible applications and limitations of individual interventions. In addition, an investigation was made to select appropriate technology based on the environmental setting.

Dendritic Cells and the Establishment of Fetomaternal Tolerance for Successful Human Pregnancy.

Pregnancy is a remarkable event where the semi-allogeneic fetus develops in the mother's uterus, despite genetic and immunological differences. The antigen handling and processing at the maternal-fetal interface during pregnancy appear to be crucial for the adaptation of the maternal immune system and for tolerance to the developing fetus and placenta. Maternal antigen-presenting cells (APCs), such as macrophages (Mφs) and dendritic cells (DCs), are present at the maternal-fetal interface throughout pregnancy and are believed to play a crucial role in this process. Despite numerous studies focusing on the significance of Mφs, there is limited knowledge regarding the contribution of DCs in fetomaternal tolerance during pregnancy, making it a relatively new and growing field of research. This review focuses on how the behavior of DCs at the maternal-fetal interface adapts to pregnancy's unique demands. Moreover, it discusses how DCs interact with other cells in the decidual leukocyte network to regulate uterine and placental homeostasis and the local maternal immune responses to the fetus. The review particularly examines the different cell lineages of DCs with specific surface markers, which have not been critically reviewed in previous publications. Additionally, it emphasizes the impact that even minor disruptions in DC functions can have on pregnancy-related complications and proposes further research into the potential therapeutic benefits of targeting DCs to manage these complications.

Emerging role of microRNAs as regulators of protein kinase C substrate MARCKS and MARCKSL1 in cancer.

MicroRNAs (miRNAs) have emerged as pivotal regulators of gene expression, playing essential roles in diverse cellular processes, including the development and progression of cancer. Among the numerous proteins influenced by miRNAs, the MARCKS/MARCKSL1 protein, a key regulator of cellular cytoskeletal dynamics and membrane-cytosol communication, has garnered significant attention due to its multifaceted involvement in various cancer-related processes, including cell migration, invasion, metastasis, and drug resistance. Motivated by the encouraging early clinical success of peptides targeting MARCKS in several pathological conditions, this review article delves into the intricate interplay between miRNAs and the MARCKS protein in cancer. Herein, we have highlighted the latest findings on specific miRNAs that modulate MARCKS/MARCKSL1 expression, providing a comprehensive overview of their roles in different cancer types. We have underscored the need for in-depth investigations into the therapeutic feasibility of targeting the miRNA-MARCKS axis in cancer, taking cues from the successes witnessed in related fields. Unlocking the full potential of miRNA-mediated MARCKS regulation could pave the way for innovative and effective therapeutic interventions against various cancer types.

Properties and physiological effects of dietary fiber-enriched meat products: a review.

Meat is a rich source of high biological proteins, vitamins, and minerals, but it is devoid of dietary fiber, an essential non-digestible carbohydrate component such as cellulose, hemicellulose, pectin, lignin, polysaccharides, and oligosaccharides. Dietary fibers are basically obtained from various cereals, legumes, fruits, vegetables, and their by-products and have numerous nutritional, functional, and health-benefiting properties. So, these fibers can be added to meat products to enhance their physicochemical properties, chemical composition, textural properties, and organoleptic qualities, as well as biological activities in controlling various lifestyle ailments such as obesity, certain cancers, type-II diabetes, cardiovascular diseases, and bowel disorders. These dietary fibers can also be used in meat products as an efficient extender/binder/filler to reduce the cost of production by increasing the cooking yield as well as by reducing the lean meat content and also as a fat replacer to minimize unhealthy fat content in the developed meat products. So, growing interest has been observed among meat processors, researchers, and scientists in exploring various new sources of dietary fibers for developing dietary fiber-enriched meat products in recent years. In the present review, various novel sources of dietary fibers, their physiological effects, their use in meat products, and their impact on various physicochemical, functional, and sensory attributes have been focused.

Molecular complexity of mammary glands development: a review of lactogenic differentiation in epithelial cells.

The mammary gland is a dynamic organ with various physiological processes like cellular proliferation, differentiation, and apoptosis during the pregnancy-lactation-involution cycle. It is essential to understand the molecular changes during the lactogenic differentiation of mammary epithelial cells (MECs, the milk-synthesizing cells). The MECs are organized as luminal milk-secreting cells and basal myoepithelial cells (responsible for milk ejection by contraction) that form the alveoli. The branching morphogenesis and lactogenic differentiation of the MECs prepare the gland for lactation. This process is governed by many molecular mediators including hormones, growth factors, cytokines, miRNAs, regulatory proteins, etc. Interestingly, various signalling pathways guide lactation and understanding these molecular transitions from pregnancy to lactation will help researchers design further research. Manipulation of genes responsible for milk synthesis and secretion will promote augmentation of milk yield in dairy animals. Identifying protein signatures of lactation will help develop strategies for persistent lactation and shortening the dry period in farm animals. The present review article discusses in details the physiological and molecular changes occurring during lactogenic differentiation of MECs and the associated hormones, regulatory proteins, miRNAs, and signalling pathways. An in-depth knowledge of the molecular events will aid in developing engineered cellular models for studies related to mammary gland diseases of humans and animals.

Preliminary Studies on the Predation of the Mite Blattisocius mali (Acari: Blattisociidae) on Various Life Stages of Spider Mite, Thrips and Fruit Fly.

Research in recent years has shown that some species of predatory mites, considered to be typically associated with soil and litter, can also be found on plants. Such species include Blattisocius mali, which is an effective predator of acarid mites, nematodes and the eggs of moths and which can disperse by means of drosophilid fruit flies. Apart from soil and litter or storage, it has also been recorded on the bark of apple trees and the leaves of strawberries, thus suggesting its possible predation of/feeding on herbivorous mites and insects. Our goal was to examine whether B. mali could consume different development stages of two polyphagous herbivores, the two-spotted spider mite, Tetranychus urticae, and the western flower thrips, Frankliniella occidentalis, as well as the drosophilid fruit fly Drosophila hydei. In 24 h cage tests, single, starved B. mali females consumed all types of prey offered, i.e., the eggs, males and females of spider mites; the first-instar larvae and prepupae of thrips; and the eggs and first-instar larvae of fruit flies. The potential for B. mali to prey upon these insects and mites was confirmed. However, to estimate whether it can also effectively reduce their population, additional tests on the predator's survival, fecundity and prey preference are needed.

Patent landscape highlighting therapeutic implications of peptides targeting myristoylated alanine-rich protein kinase-C substrate (MARCKS).

INTRODUCTION: MARCKS protein, a protein kinase C (PKC) substrate, is known to be at the intersection of several intracellular signaling pathways and plays a pivotal role in cellular physiology. Unlike PKC inhibitors, MARCKS-targeting drug (BIO-11006) has shown early success in clinical trials involving lung diseases. Recent research investigations have identified two MARCKS-targeting peptides which possess multifaceted implications against asthma, cancer, inflammation, and lung diseases. AREAS COVERED: This review article provides the patent landscape and recent developments on peptides targeting MARCKS for therapeutic purposes. Online free open-access databases were used to fetch out the patent information, and research articles were fetched using PubMed. EXPERT OPINION: Research studies highlighting the intriguing role of MARCKS in human disease and physiology have dramatically increased in recent years. A similar increasing trend in the number of patents has also been observed related to the MARCKS-targeting peptides. Thus, there is a need to amalgamate and translate such a trend into therapeutic intervention. Our review article provides an overview of such recent advances, and we believe that our compilation will fetch the interest of researchers around the globe to develop MARCKS-targeting peptides in future for human diseases.

Proteomic Approaches to Unravel the Molecular Dynamics of Early Pregnancy in Farm Animals: An In-Depth Review.

Infertility is a major problem in farm animals, which has a negative economic effect on farm industries. Infertility can be defined as the inability of animals to achieve a successful pregnancy. Early pregnancy is crucial to establish a successful pregnancy, and it is reported that 70-80% and 20-30% of total embryonic loss occur in cattle and pigs, respectively, during the first month of pregnancy. The advanced high-throughput proteomics techniques provide valuable tools for in-depth understanding of the implantation process in farm animals. In the present review, our goal was to compile, assess, and integrate the latest proteomic research on farm animals, specifically focused on female reproduction, which involves endometrial tissues, uterine fluids, oviductal fluids, and microRNAs. The series of studies has provided in-depth insights into the events of the implantation process by unfolding the molecular landscape of the uterine tract. The discussed data are related to pregnant vs. non-pregnant animals, pregnancy vs. oestrous cycle, different days of the early pregnancy phase, and animals with uterine infections affecting reproduction health. Some of the studies have utilized non-invasive methods and in vitro models to decipher the molecular events of embryo-maternal interaction. The proteomics data are valuable sources for discovering biomarkers for infertility in ruminants and new regulatory pathways governing embryo-uterine interaction, endometrium receptivity, and embryonic development. Here, we envisage that the identified protein signatures can serve as potential therapeutic targets and biomarkers to develop new therapeutics against pregnancy diseases.

Critical Review on Physiological and Molecular Features during Bovine Mammary Gland Development: Recent Advances.

The mammary gland is a unique organ with the ability to undergo repeated cyclic changes throughout the life of mammals. Among domesticated livestock species, ruminants (cattle and buffalo) constitute a distinct class of livestock species that are known milk producers. Cattle and buffalo contribute to 51 and 13% of the total milk supply in the world, respectively. They also play an essential role in the development of the economy for farming communities by providing milk, meat, and draft power. The development of the ruminant mammary gland is highly dynamic and multiphase in nature. There are six developmental stages: embryonic, prepubertal, pubertal, pregnancy, lactation, and involution. There has been substantial advancement in our understanding of the development of the mammary gland in both mouse and human models. Until now, there has not been a thorough investigation into the molecular processes that underlie the various stages of cow udder development. The current review sheds light on the morphological and molecular changes that occur during various developmental phases in diverse species, with a particular focus on the cow udder. It aims to explain the physiological differences between cattle and non-ruminant mammalian species such as humans, mice, and monkeys. Understanding the developmental biology of the mammary gland in molecular detail, as well as species-specific variations, will facilitate the researchers working in this area in further studies on cellular proliferation, differentiation, apoptosis, organogenesis, and carcinogenesis. Additionally, in-depth knowledge of the mammary gland will promote its use as a model organ for research work and promote enhanced milk yield in livestock animals without affecting their health and welfare.

Deep Insight of the Pathophysiology of Gestational Diabetes Mellitus.

Diabetes mellitus is a severe metabolic disorder, which consistently requires medical care and self-management to restrict complications, such as obesity, kidney damage and cardiovascular diseases. The subtype gestational diabetes mellitus (GDM) occurs during pregnancy, which severely affects both the mother and the growing foetus. Obesity, uncontrolled weight gain and advanced gestational age are the prominent risk factors for GDM, which lead to high rate of perinatal mortality and morbidity. In-depth understanding of the molecular mechanism involved in GDM will help researchers to design drugs for the optimal management of the condition without affecting the mother and foetus. This review article is focused on the molecular mechanism involved in the pathophysiology of GDM and the probable biomarkers, which can be helpful for the early diagnosis of the condition. The early diagnosis of the metabolic disorder, most preferably in first trimester of pregnancy, will lead to its effective long-term management, reducing foetal developmental complications and mortality along with safety measures for the mother.

Role of Natural Killer Cells during Pregnancy and Related Complications.

A high number of leucocytes reside in the human endometrium and are distributed differentially during the menstrual cycle and pregnancy. During early pregnancy, decidual natural killer (dNK) cells are the most common type of natural killer (NK) cells in the uterus. The increase in the number of uterine NK (uNK) cells during the mid-secretory phase of the menstrual cycle, followed by further increase of dNK cells in early pregnancy, has heightened interest in their involvement during pregnancy. Extensive research has revealed various roles of dNK cells during pregnancy including the formation of new blood vessels, migration of trophoblasts, and immunological tolerance. The present review article is focused on the significance of NK cells during pregnancy and their role in pregnancy-related diseases. The article will provide an in-depth review of cellular and molecular interactions during pregnancy and related disorders, with NK cells playing a pivotal role. Moreover, this study will help researchers to understand the physiology of normal pregnancy and related complications with respect to NK cells, so that future research work can be designed to alleviate the complications.

Multifaceted Pharmacological Potentials of Curcumin, Genistein, and Tanshinone IIA through Proteomic Approaches: An In-Depth Review.

Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future.

Probiotics: A Promising Candidate for Management of Colorectal Cancer.

Colorectal cancer (CRC) is the World's third most frequently diagnosed cancer type. It accounted for about 9.4% mortality out of the total incidences of cancer in the year 2020. According to estimated facts by World Health Organization (WHO), by 2030, 27 million new CRC cases, 17 million deaths, and around 75 million people living with the disease will appear. The facts and evidence that establish a link between the intestinal microflora and the occurrence of CRC are quite intuitive. Current shortcomings of chemo- and radiotherapies and the unavailability of appropriate treatment strategies for CRC are becoming the driving force to search for an alternative approach for the prevention, therapy, and management of CRC. Probiotics have been used for a long time due to their beneficial health effects, and now, it has become a popular candidate for the preventive and therapeutic treatment of CRC. The probiotics adopt different strategies such as the improvement of the intestinal barrier function, balancing of natural gut microflora, secretion of anticancer compounds, and degradation of carcinogenic compounds, which are useful in the prophylactic treatment of CRC. The pro-apoptotic ability of probiotics against cancerous cells makes them a potential therapeutic candidate against cancer diseases. Moreover, the immunomodulatory properties of probiotics have created interest among researchers to explore the therapeutic strategy by activating the immune system against cancerous cells. The present review discusses in detail different strategies and mechanisms of probiotics towards the prevention and treatment of CRC.

Role of Fibulins in Embryonic Stage Development and Their Involvement in Various Diseases.

The extracellular matrix (ECM) plays an important role in the evolution of early metazoans, as it provides structural and biochemical support to the surrounding cells through the cell-cell and cell-matrix interactions. In multi-cellular organisms, ECM plays a pivotal role in the differentiation of tissues and in the development of organs. Fibulins are ECM glycoproteins, found in a variety of tissues associated with basement membranes, elastic fibers, proteoglycan aggregates, and fibronectin microfibrils. The expression profile of fibulins reveals their role in various developmental processes such as elastogenesis, development of organs during the embryonic stage, tissue remodeling, maintenance of the structural integrity of basement membrane, and elastic fibers, as well as other cellular processes. Apart from this, fibulins are also involved in the progression of human diseases such as cancer, cardiac diseases, congenital disorders, and chronic fibrotic disorders. Different isoforms of fibulins show a dual role of tumor-suppressive and tumor-promoting activities, depending on the cell type and cellular microenvironment in the body. Knockout animal models have provided deep insight into their role in development and diseases. The present review covers details of the structural and expression patterns, along with the role of fibulins in embryonic development and disease progression, with more emphasis on their involvement in the modulation of cancer diseases.

TMT based deep proteome analysis of buffalo mammary epithelial cells and identification of novel protein signatures during lactogenic differentiation.

The lactating mammary gland harbours numerous matured alveoli with their lumen surrounded by differentiated mammary epithelial cells (MECs), which are exclusively involved in milk synthesis and secretion. Buffalo (Bubalus bubalis) is the second major milk-producing animal, and its physiology is different from cattle. The complete protein machinery involved in MECs differentiation is still not defined in ruminants, in particular, buffalo. Therefore, we have studied the differential expression of regulated proteins in the in vitro grown buffalo MECs (BuMECs) at different time points (on 3, 6, 12, and 15 days) of their differentiation in the presence of lactogenic hormones. TMT-based MS analysis identified 4,934 proteins; of them, 681 were differentially expressed proteins (DEPs). The principal component analysis suggested a highly heterogeneous expression of DEPs at the four-time points of hormone treatment, with most of them (307) attained the highest expression on 12 days. Bioinformatics analysis revealed the association of DEPs with 24 KEGG pathways. We observed few new proteins, namely ABCA13, IVL, VPS37, CZIB, RFX7, Rab5, TTLL12, SMEK1, GDI2, and TMEM131 in BuMECs. The function of one of the highly upregulated proteins, namely involucrin in the differentiation of BuMECs was confirmed based on biochemical inhibition assay. The results further conclude that the proteins with higher abundance can be considered as the potential biomarkers for differentiation, and they may have a significant association with the lactation process in buffalo too. The proteome dataset obtained can be used to understand the species-specific variations among other lactating animals.

Reverse vaccinology approach towards the in-silico multiepitope vaccine development against SARS-CoV-2.

Background: The novel severe acute respiratory syndrome related corona virus-2 (SARS-CoV-2) belongs to the "Coronaviridae" family and order "Nidovirales", which has caused the pandemic coronavirus disease 2019 (COVID-19). SARS-CoV-2 has been spread in more than a 100 countries, and more than a million have lost their lives. Vaccination and immunization could be an effective strategy to combat fatal COVID-19. Methods: For identification of effective vaccine candidate against COVID-19, various immunoinformatics online tools and softwares were used to predict epitopes. Cytotoxic T cell epitopes, helper T cell epitopes, and B cell epitopes from three structural polyproteins (Spike, Membrane, and Nucleocapsid (SMN) based on the binding affinity towards MHC, antigenicity, non-allergenicity, and non-toxicity) were identified for vaccine development. The multiepitope based vaccine was constructed linking two additional adjuvants human beta-defensin-3 and human beta-defensin-2 at N and C terminal, respectively. Results: The constructed vaccine sequence was found to be a good antigen and non-allergen for the human body. The constructed vaccine was docked with the TLR-3 receptor.  The docked complex was further taken for molecular dynamics simulations and RMSD was calculated, which showed stable binding of the complex. The codon adaptation index (CAI) of 0.92 and GC content of 55.5% for E. coli (K12 strain) suggested efficient expression of the predicted vaccine. Conclusion: The current study can be helpful in the reduction of time and cost for further experimental validations and could give a valuable contribution against this pandemic.

In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19.

The recent outbreak of the novel coronavirus (SARS-CoV-2) in the Wuhan province of China has taken millions of lives worldwide. In this pandemic situation and absence of known drugs and vaccines against novel coronavirus disease (COVID-19), there is an urgent need for the repurposing of the existing drugs against it. So, here we have examined a safe and cheap alternative against this virus by screening hundreds of nutraceuticals compounds against known therapeutic targets of SARS-COV-2 by molecular docking. The virtual screening results were then analyzed for binding energy and interactive residues and compared with some already known hits in the best binding pose. All these analyses of this study strongly predicted the potential of Folic acid and its derivates like Tetrahydrofolic acid and 5-methyl tetrahydrofolic acid against SARS-COV-2. The strong and stable binding affinity of this water-soluble vitamin and its derivatives against the SARS-COV-2, indicating that they could be valuable drugs against the management of this COVID-19 pandemic. This study could serve as the starting point for further investigation of these molecules through in vitro and in vivo assays.

Pathogenesis of Preeclampsia and Therapeutic Approaches Targeting the Placenta.

Preeclampsia (PE) is a serious pregnancy complication, affecting about 5-7% of pregnancies worldwide and is characterized by hypertension and damage to multiple maternal organs, primarily the liver and kidneys. PE usually begins after 20 weeks' gestation and, if left untreated, can lead to serious complications and lifelong disabilities-even death-in both the mother and the infant. As delivery is the only cure for the disease, treatment is primarily focused on the management of blood pressure and other clinical symptoms. The pathogenesis of PE is still not clear. Abnormal spiral artery remodeling, placental ischemia and a resulting increase in the circulating levels of vascular endothelial growth factor receptor-1 (VEGFR-1), also called soluble fms-like tyrosine kinase-1 (sFlt-1), are believed to be among the primary pathologies associated with PE. sFlt-1 is produced mainly in the placenta during pregnancy and acts as a decoy receptor, binding to free VEGF (VEGF-A) and placental growth factor (PlGF), resulting in the decreased bioavailability of each to target cells. Despite the pathogenic effects of increased sFlt-1 on the maternal vasculature, recent studies from our laboratory and others have strongly indicated that the increase in sFlt-1 in PE may fulfill critical protective functions in preeclamptic pregnancies. Thus, further studies on the roles of sFlt-1 in normal and preeclamptic pregnancies are warranted for the development of therapeutic strategies targeting VEGF signaling for the treatment of PE. Another impediment to the treatment of PE is the lack of suitable methods for delivery of cargo to placental cells, as PE is believed to be of placental origin and most available therapies for PE adversely impact both the mother and the fetus. The present review discusses the pathogenesis of PE, the complex role of sFlt-1 in maternal disease and fetal protection, and the recently developed placenta-targeted drug delivery system for the potential treatment of PE with candidate therapeutic agents.

Role of Macrophages in Pregnancy and Related Complications.

Macrophages (MФs) are the leukocytes produced from differentiation of monocytes and are located in almost all tissues of human body. They are involved in various processes, such as phagocytosis, innate and adaptive immunity, proinflammatory (M1) and anti-inflammatory (M2) activity, depending on the tissue microenvironment. They play a crucial role in pregnancy, and their dysfunction or alteration of polarity is involved in pregnancy disorders, like preeclampsia, recurrent spontaneous abortion, infertility, intrauterine growth restriction, and preterm labor. About 50-60% of decidual leukocytes are natural killer (NK) cells followed by MФs (the second largest population). MФs are actively involved in trophoblast invasion, tissue and vascular remodeling during early pregnancy, besides their role as major antigen-presenting cells in the decidua. These cells have different phenotypes and polarities in different stages of pregnancy. They have also been observed to enhance tumor growth by their anti-inflammatory activity (M2 type) and prevent immunogenic rejection. Targeted alteration of polarity (M1-M2 or vice versa) could be a major focus in the future treatment of pregnancy complications. This review is focused on the role of MФs in pregnancy, their involvement in pregnancy disorders, and decidual MФs as possible therapeutic targets for the treatment of pregnancy complications.

Molecular mechanism of mammary gland involution: An update.

The mammary gland (MG) is a unique organ responsible for milk synthesis, secretion, and involution to prepare the gland for subsequent lactation. The mammary epithelial cells (MECs), which are the milk synthesizing units of the MG, proliferate, differentiate, undergo apoptosis and regenerate following a cyclic pathway of lactation - involution - lactation, fine-tuning these molecular events through hormones, growth factors and other regulatory molecules. The developmental stages of the MG are embryonic, prepubertal, pubertal, pregnancy, lactation and involution, with major developmental processes occurring after puberty. The involution stage includes interesting physiological processes such as MEC apoptosis, matrix remodeling, and the generation of cells regaining the shape of a virgin MG. Signal transducer and activator of transcription 3 (STAT3) is the established master regulator of this process and aberrant expression of STAT3 leads to subnormal involution and may induce neoplasia. Several studies have reported on the molecular mechanism of MG involution with substantial knowledge being gained about this process; however, a deep understanding of this phenomenon has yet to be attained. This review focuses deeply on the molecular details of post-lactational regression, the signaling pathways involved in the lactation-involution cycle, and the latest developments in STAT3-associated MG neoplasia. Deep insight into the involution process will pave the way towards understanding the biology, apoptosis, and oncogenesis of the MG.