Search

Abstract Background The Androgen Receptor (AR) has emerged as an endocrine therapy target in Breast Cancer, exhibiting up to 80% expression in clinical cases. AR-V7, a constitutively activated splice variant of AR with a truncated ligand-binding domain (LBD), demonstrates ligand-independent transcriptional activity and resistance to nonsteroidal antiandrogens like Bicalutamide or Enzalutamide, targeting the LBD. In metastatic prostate cancer, elevated AR-V7 levels lead to therapeutic resistance and increased metastasis. Methods In this study, we evaluated the expression of AR and AR-V7 in cell lines and a cohort of 89 patients undergoing surgical intervention for treatment-naïve breast cancer. Further clinicopathological correlations and survival analysis were performed to evaluate the relationship between the AR and AR-V7 expression and clinical outcomes. Results AR-V7/AR-FL ratio was elevated in the TNBC cell line and downregulation of AR-FL upon AR antagonists’ treatment led to a compensatory increase in AR-V7. Clinical samples showed significantly elevated expression of AR and AR-V7 in tumors compared to control cases. Further clinicopathological correlation revealed aggressive clinical traits, higher pathological grades, and poor survival with AR-V7 expression. Conclusions Our study unravels AR-V7 as a marker for poor clinical outcomes, predicting breast cancer aggressiveness, and encourages consideration of AR-V7 as a probable target for therapeutic intervention.

Gallbladder cancer (GBC) starts in the epithelial tissue (lining of the bile duct and gallbladder). It is a type of aggressive cancer called adenocarcinoma that can spread to other tissues. Among all cases of biliary tract cancer, 50% is from GBC. It is a deadly cancer with a survival rate of 17.6% between 2007 and 2013. GBC is rarely found in the Western world, but it is commonly found in South Asia. In Southeast Asian countries, GBC plays a significant role in cancer-related morbidity and mortality. GBC incidence exhibits marked regional variability, a rare condition in the western population but having a higher frequency in India, especially the Indo-Gangetic belt and some northeast districts excluding Nagaland. This might be attributed to the differences in environmental factors and genetic predisposition modulating carcinogenesis. In GBC, only 10% of cases are identified in the early stages. The low rate of early detection is due to the lack of screening techniques and the aggressive characteristics of the tumor. Various risk factors are associated with GBC, for example, chronic cholecystitis with or without gallstones, obesity, exposure to heavy metals such as lead and arsenic, bacterial infection, congenital biliary cysts, and abnormal pancreaticobiliary duct junction. The risk factors can cause chronic gallbladder mucosa irritation, leading to dysplasia and neoplasia. GBC can form metaplasia to dysplasia in a time span of 5–15 years, then to carcinoma in situ, and finally to invasive cancer. Dysbiosis is responsible for various diseases, including cancer. Multiple triggers can cause dysbiosis, for example, environmental changes, inflammation, infection, medications, dietary changes, or genetic predisposition. Various researches show that Helicobacter pylori, human papillomavirus, Hepatitis B virus, and Hepatitis C virus microbial species can cause cancer. They are the major species responsible for 90% of infection-associated cancers. Various studies demonstrate that the strains of Salmonella and Helicobacter colonize are linked to developing GBC. While the mechanisms linking gut microbiota to GBC are not fully understood, several studies have suggested a potential association. According to a study, certain gut microbiomes, such as Fusobacterium nucleatum, found glut in GBC tissues, compared to adjacent normal tissues. By evaluating gut microbiome dysbiosis, we can see the potential link between gut microbiome dysbiosis and GBC; it may provide valuable insights into the development and progression of GBC. It could lead to the identification of new diagnostic markers and the development of novel therapeutic strategies. In GBC, the evaluation of gut microbiome dysbiosis (involving evaluating the composition, diversity, and functional capacity of the gut microbiome in patients) has emerged as a promising method for understanding the molecular mechanisms and identifying biomarkers for early prevention and detection of GBC and also investigating the possibility of any link between the gut microbiome and host immune response. In conclusion, evaluating gut microbiome dysbiosis in GBC is a promising direction for identifying potential early detection and prevention biomarkers. Additional investigation is therefore needed to determine the role of gut microbiome dysbiosis in the development and progression of GBC and to identify reliable biomarkers for clinical use.

DNA that is found outside the main chromosomes in a cell's nucleus is known as extrachromosomal DNA. This type of DNA is not part of the standard 23 pairs of chromosomes in humans and instead exists as standalone circular or linear DNA structures. Unlike bacterial plasmids, extrachromosomal DNA in human cells contains important genetic material and holds particular significance in cancer cells. Critical characteristics of ecDNA in Cancer is that they frequently harbour amplified versions of oncogenes such as MYC, EGFR, and CCND1. These oncogenes propel the growth and survival of tumors. Cancer cells utilize ecDNA to generate multiple copies of these oncogenes, amplifying their expression without requiring alterations to the chromosomal structure. This amplification grants the cancer cells a competitive edge in growth. ecDNA plays a crucial role in the advancement and growth of cancer, as it amplifies oncogenes, genetic diversity, and resistance to treatments. Its adaptable and ever-changing characteristics empower cancer cells to adjust to external influences such as medication. Gaining insights into ecDNA's operations and impacts could lead to new possibilities for diagnosing and treating cancer, as well as developing therapies aimed at this distinct DNA structure.

The coronavirus disease 2019 (COVID-19) pandemic cost 7–8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in acute respiratory distress syndrome (ARDS) and lung injury. Anti-inflammatory intervention with anti-interleukin-6 (anti-IL-6) receptor monoclonal antibodies (mAbs; e.g., sarilumab and tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and/or steroid-based approach leads to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this review, the authors have summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus-host immune cross talks and presenting the possibilities of therapeutic intervention.

Enhancer elements are specific DNA sequences that play a crucial role in regulating gene expression. Located upstream or downstream in the genomic context, enhancers enhance the transcription of linked genes. This is achieved by providing binding sites for transcription factors and other proteins, acting as a nucleation point that promotes the assembly of the transcriptional machinery. What makes enhancers unique is that located even thousands of base pairs away, they can exert their function. They can act over long distances, looping to interact with the promoter region of their target genes. Enhancers are often involved in cell type-specific gene expression as different cells express different sets of genes by activating and repressing cell type-specific enhancers. Cancer cells seem to co-opt this mechanism and hijack it for their own survival. In this process, an aberrant enhancer element activates the transcription of oncogenes (genes that have the potential to cause cancer) due to some alterations in genomic structure or regulatory elements that happen in cancer, contributing to tumorigenesis and cancer progression. Enhancer hijacking often occurs through complex genomic rearrangements such as chromosomal translocations and other structural rearrangements such as deletions or amplifications.8 These alterations can bring a usually distant, far-located enhancer into proximity with an oncogene, leading to its inappropriate activation. This is often seen in various cancers, including leukemias and solid tumors. Enhancer hijacking and its effects on gene regulation in cancer are frequently studied using methods such as RNA sequencing, chromatin conformation capture, and CRISPR-Cas9. Finding an enhancer hijacking event may be used to inform treatment choices, especially in precision medicine settings, and may also function as a biomarker for particular cancer types.

According to sociologist, Sylvia patriarchy is “a system of social structures and practices in which men dominate, oppress, and exploit women.” Derived from the Greek word patriarkhēs, patriarchy means “the rule of the father.” American sociologist Allan Johnson further mentions that patriarchy is a kind of society in which even though men and women participate, but is male-privileged, maledominated, male-identified, and male-centered. Apart from the sociologist’s point of view of society, it seems that developmental programs in biology also have a patriarchal trend. At least, that’s what is reported from several studies recently. Lopez-Tello et al., reported a paternal insulinlike growth factor 2 (Igf2)-related selective trafficking of maternal resources toward the fetus for its development. Metabolic demands for the fetus are enhanced during pregnancy. It is, therefore, observed that there is a relatively greater shunting of metabolic fuels toward the fetus to increase nutrient availability, more than it is perhaps allowed by the maternal system. The placenta assists in this shuttle by promoting insulin resistance, which leads to glucose intolerance in the mother. This glucose is now made available to the fetal compartments. The paternal Igf2 gene undergoes genomic imprinting, and only the copy inherited from the father is active. Paternally active Igf2 expressed in placental endocrine cells directs the maternal lipids and carbohydrates toward the fetus, an excellent example of paternal manipulation of maternal physiology and metabolic patriarchy. Further, studies have shown that fathers fed with a high-fat diet reduce the pregnancy success rate because of the reduction of their sperm motility. Excess intake of processed food, highsugar diets, or fructose has consequences on offspring’s cardiovascular and metabolic diseases. Males fed a low protein diet in mice results in glucose intolerance, metabolic and cardiovascular dysfunctions, and altered patterns of bone mineralization in pups. We, therefore, can conclude a robust paternal influence on pregnancy and fetal outcome. Pregnancy was once thought of as an exclusively maternal affair. Increasing research in this arena seems to have smashed that stereotype with paternal influence seems to play a significant role in shaping the birth process. It is high time that Sylvia patriarchal understanding is redefined with the paternal share of responsibility beyond just dominance and an authoritarian role.

Emergence of new variants of COVID-19 is nothing new. Different variants evolved with additional mutations of the virus as part of the viral replication cycle have different infectious properties. JN.1 is the latest COVID-19 variant that seems to circulate the globe contributing to many infections and hospitalizations labeling it a variant of interest by the WHO. The scientific community has yet to understand its full lethal potential if any. In this mini-review, we summarized the facts known so far about this variant and its possible consequences if any for humanity.

Bioluminescent imaging (BLI) has emerged as a powerful tool in cancer research, allowing for non-invasive, real-time monitoring of various aspects of cancer biology in vivo. This technique relies on the expression of bioluminescent reporter genes in cancer cells, enabling the visualization of tumor growth, metastasis, and response to treatment. In this review, we provide an overview of the principles underlying BLI, its applications in cancer research, and the potential advantages and limitations of this technology.

Abstract Background Myelodysplastic Neoplasms (MDS) are clonal stem cell disorders characterized by ineffective hematopoiesis and progression to acute myeloid leukemia, myelodysplasia-related (AML-MR). A major mechanism of pathogenesis of MDS is the aberration of the epigenetic landscape of the hematopoietic stem cells and/or progenitor cells, especially DNA cytosine methylation, and demethylation. Data on TET2, the predominant DNA demethylator of the hematopoietic system, is limited, particularly in the MDS patients from India, whose biology may differ since these patients present at a relatively younger age. We studied the expression and the variants of TET2 in Indian MDS and AML-MR patients and their effects on 5-hydroxymethyl cytosine (5-hmC, a product of TET2 catalysis) and on the prognosis of MDS patients. Results Of the 42 MDS patients, cytogenetics was available for 31 sub-categorized according to the Revised International Prognostic Scoring System (IPSS-R). Their age resembled that of the previous studies from India. Bone marrow nucleated cells (BMNCs) were also obtained from 13 patients with AML-MR, 26 patients with de-novo AML, and 11 subjects with morphologically normal bone marrow. The patients had a significantly lower TET2 expression which was more pronounced in AML-MR and the IPSS-R higher-risk MDS categories. The 5-hmC levels in higher-risk MDS and AML-MR correlated with TET2 expression, suggesting a possible mechanistic role in the loss of TET2 expression. The findings on TET2 and 5-hmC were also confirmed at the tissue level using immunohistochemistry. Pathogenic variants of TET2 were found in 7 of 24 patient samples (29%), spanning across the IPSS-R prognostic categories. One of the variants – H1778R – was found to affect local and global TET2 structure when studied using structural predictions and molecular dynamics simulations. Thus, it is plausible that some pathogenic variants in TET2 can compromise the structure of TET2 and hence in the formation of 5-hmC. Conclusions IPSS-R higher-risk MDS categories and AML-MR showed a reduction in TET2 expression, which was not apparent in lower-risk MDS. DNA 5-hmC levels followed a similar pattern. Overall, a decreased TET2 expression and a low DNA 5-hmC level are predictors of advanced disease and adverse outcome in MDS in the population studied, i.e., MDS patients from India.

When it comes to longevity, everyone wants to live for eternity. Longevity research has often led scientists to dark alleys with several candidate molecules responsible for aging. Pioneering genetic studies on model organisms like Caenorhabditis elegans and Drosophila melanogaster discovered the most well-conserved longevity pathways, mainly caloric restriction and the insulin/insulin-like growth factor 1signaling pathways. Apart from these complex molecular circuitries that drive longevity, a recent study published by Zipple et al. (Proceedings of the National Academy of Sciences, 2024) showed that the relationship between mother and grandmother with the child may determine why some animals and humans live longer than expected for their size. Animals that spend more time with their mothers during early life end up living longer but with reduced capacity to produce offspring. This exciting piece of research has far more consequences than just these findings. It implies the importance of the mother in one’s life and the role of parental care in providing longevity and reproductive success.

Semaglutide (Ozempic acid) belongs to a class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists. These medications mimic the action of a hormone called GLP-1, which helps regulate blood glucose and promotes weight loss. One role of GLP-1 is to prompt the body to produce more insulin, which reduces blood sugar (glucose). Because of this, doctors have been treating type 2 diabetes with semaglutide for more than 15 years. Higher doses of GLP-1, however, also cause anoxia by interacting with the brain regions responsible for appetite suppression. When combined with diet and exercise, it can help people who are obese or overweight lose a significant amount of weight and lower their risk of developing diabetes, heart disease, and cancer. This effect of Semaglutide made it an appropriate candidate for weight loss. At present, semaglutide is only approved for weight loss under the brand name Wegovy. Public demand and craze for weight loss have prompted the usage and misusage of semaglutide. As interest and obsession with weight loss programs continue to grow, health-care professionals are forced to improvise their strategy to manage the demand. One way to meet needs is to prescribe other brands of semaglutide, such as Ozempic and Rybelsus (using a Food and Drug Administration [FDA]-approved drug for a different reason). The FDA recommends Wegovy for weight loss if you meet one of the following criteria: The FDA guidelines for semaglutide usage only if body mass index (BMI) is 27 kg/m2 or greater along with other co-morbidities such as high blood pressure, type 2 diabetes, or high cholesterol or a BMI >30 kg/m2. This has become so rampant that genuine users of semaglutide who need it for managing their blood sugar are finding it missing from the shelf. Overuse or improper use often comes with adverse consequences, such as hypoglycemia, confusion, dizziness, seizures, headache, and even loss of consciousness. The craze for semaglutide needs to be cautiously weighed before consumption.

Anemia has been a significant public health concern in India, especially among women and children. The National Family Health Survey (NFHS) is one of the primary sources of health-related data in India. The NFHS-4, conducted in 2015–2016, reported that around 53% of women aged 15–49 in India were anemic. The symptoms of depression, a serious psychiatric condition, include low mood, energy loss, low self-esteem, and both physical and psychological sluggishness. According to the 2019 Global Burden of Disease Study, depression is one of the most incapacitating mental diseases. Depression and related psychological illnesses and physical discomfort have an impact on the health and quality of life. Although seems disconnected, there are some potential molecular links between depression and anemia. Both depression and anemia are associated with inflammation. Chronic inflammation has the potential to impact the generation and operation of red blood cells in anemia, as well as play a role in neuroinflammation that affects neurotransmitter systems linked to depression, such as serotonin and dopamine pathways. Depression is often associated with irregularities in neurotransmitters such as serotonin, dopamine, and norepinephrine, which not only influence mood but also have implications for erythropoiesis and iron metabolism. The dysregulation of the HPA axis in depression can result in heightened cortisol levels and changes in stress response, affecting erythropoiesis and iron metabolism, thus contributing to anemia. Nutritional deficiencies, particularly in Vitamins B12 and folate, can also lead to both anemia and mood disturbances, including symptoms of depression, as these nutrients are crucial for proper erythropoiesis and neurotransmitter synthesis. We, however, need to note that not all cases of depression or anemia are directly linked in every individual. The relationship between these conditions can be complex and multifactorial, influenced by various genetic, environmental, and physiological factors. What is more important is that there are real possibilities of a potential cross-talk between the two. Managing anemia in women is therefore of prime importance both for health issues as well as for mood and psychological well-being.

SKP2 (S-phase kinase-associated protein 2) is a member of the F-box family of substrate-recognition subunits in the SCF ubiquitin-protein ligase complexes. It is associated with ubiquitin-mediated degradation in the mammalian cell cycle components and other target proteins involved in cell cycle progression, signal transduction, and transcription. Being an oncogene in solid tumors and hematological malignancies, it is frequently associated with drug resistance and poor disease outcomes. In the current review, we discussed the novel role of SKP2 in different hematological malignancies. Further, we performed a limited in-silico analysis to establish the involvement of SKP2 in a few publicly available cancer datasets. Interestingly, our study identified Skp2 expression to be altered in a cancer-specific manner. While it was found to be overexpressed in several cancer types, few cancer showed a down-regulation in SKP2. Our review provides evidence for developing novel SKP2 inhibitors in hematological malignancies. We also investigated the effect of SKP2 status on survival and disease progression. In addition, the role of miRNA and its associated families in regulating Skp2 expression was explored. Subsequently, we predicted common miRNAs against Skp2 genes by using miRNA-predication tools. Finally, we discussed current approaches and future prospective approaches to target the Skp2 gene by using different drugs and miRNA-based therapeutics applications in translational research.

Smartwatches have emerged as powerful tools for health monitoring in recent years. These wearable devices combine advanced technology with portability, enabling individuals to track various aspects of their health and well-being conveniently. Heart rate monitoring has several advantages. Many smartwatches are equipped with optical heart rate sensors that continuously monitor a user’s heart rate. This feature provides real-time data on heart rate variations, which can be crucial for identifying irregularities and assessing overall cardiovascular health. Activity tracking: Smartwatches often include accelerometers and gyroscopes that track physical activities such as steps taken, distance traveled, and calories burned. This information can aid in setting and achieving fitness goals. Sleep tracking:Some smartwatches offer sleep tracking features, recording sleep duration, quality, and patterns. These data help users understand their sleep habits and make improvements for better rest. Global positioning system (GPS) and location tracking: Integrated GPS allows users to track their outdoor activities accurately, including running and cycling. This feature not only measures performance but also enhances safety during workouts. Stress monitoring: Certain smartwatches include tools that measure stress levels through heart rate variability analysis. Users can learn to manage stress more effectively based on these data. Electrocardiogram (ECG) and blood pressure monitoring:High-end smartwatches may include ECG and blood pressure monitoring capabilities. These features are particularly useful for individuals with heart conditions or hypertension. Notifications and alerts: Smartwatches can deliver notifications and alerts related to health goals, reminders to move, medication schedules, and emergencies. This functionality enhances user engagement and timely interventions. BENEFITS OF SMARTWATCHES IN HEALTH MONITORING Unlike periodic doctor visits, smartwatches enable continuous health monitoring. Users can track their vital signs and activities throughout the day, providing a more comprehensive picture of their health. Smartwatches empower individuals to take control of their health. Users can make informed decisions about their lifestyle, exercise, and diet by providing real-time data. Smartwatches equipped with ECG and heart rate monitoring can detect irregularities and abnormalities early on. This early detection can be lifesaving for individuals at risk of heart-related conditions. Activity tracking and goal-setting features motivate users to engage in physical activities and maintain a healthier lifestyle. Achieving fitness goals can lead to increased motivation and adherence to healthier habits. Health data collected by smartwatches can be used to tailor fitness and wellness plans to an individual’s specific needs. This personalized approach can lead to more effective health improvements. LIMITATIONS AND CONSIDERATIONS Accuracy: While smartwatches offer valuable health data, their accuracy may vary. Factors such as skin type,device placement, and motion can affect the precision of measurements. Battery life: Continuous health monitoring can drain a smartwatch’s battery quickly. Users may need to recharge their devices frequently, potentially limiting the monitoring duration. Privacy and data security: Storing sensitive health data on a smartwatch raise concerns about privacy and data security. Manufacturers must implement robust security measures to protect users’ information. User reliance: There is a risk of over-reliance on smartwatches for health information. Users should be encouraged to consult health-care professionals for a comprehensive health assessment. CONCLUSION Smartwatches have become versatile tools for health monitoring, offering a range of features that empower users to track and improve their well-being. While they have numerous benefits, users should know their limitations and use them as complementary tools in their health-care journey. Manufacturers and health-care providers play a critical role in ensuring the accuracy and security of the health data collected by these devices.

In this review, we elaborate the post-COVID-19 challenges, and also, the lesson learned out of this crisis. With over 700 million people affected worldwide and nearly 6 million deaths, COVID-19 pandemic is of unprecedented nature ever witnessed by the human race. Besides health-care challenges, there were socioeconomic consequences that still have its footprints affecting life of the citizens. We summarized these challenges, addressing the lacunae in terms of enhancing our infrastructure, logistics, and knowledge, not only about this disease, but also to adequately prepare for future pandemic of this proportion.

Traditional in-vitro 2D cell culture-based models have limitations in cancer research, as they do not accurately reflect the complex 3D architecture and interactions we find in tumors. Cell-cell communications are vital for cancer growth and proliferation. Cancer cells communicate with each other and surrounding cells through various pathways, sending signals that promote their growth, survival, and proliferation through autocrine, paracrine, and endocrine. Fundamentally, this communication forms the basis of cancer survival. This can involve growth factors, cytokines, and other molecules that activate essential signaling pathways for tumor growth. Cancer cells need constant blood and nutrients to sustain such massive growth. This is again achieved by communication with endothelial cells to stimulate the formation of new blood vessels to sustain their energy and metabolic needs. The conventional 2D and 3D cultures play a role in oncology research, but each has its strengths and weaknesses when it comes to studying cancer. While 2D culture systems are simple, easier, and inexpensive to set up and maintain, 3D cultures are more realistic representations of actual tumors due to their 3D structure and cell-cell interactions. They can capture the genetic and functional heterogeneity of patient-derived tumors, thereby allowing for modeling the tumor microenvironment with various cell types and signaling and immune molecules. 2D culture fails to accurately reflect the complex 3D architecture and interactions of cells as seen in vivo due to their limited ability to model cell-cell interactions and the tumor microenvironment. 3D culture-derived organoids behave like miniature, simplified organs in vitro, which can be used for drug testing, disease modeling, and regenerative medicine applications. By creating conditions mimicking embryonic development, 3D culture can be used to study organogenesis and tissue morphogenesis.3D culture models can also be used to study the interaction between pathogens and host cells, providing a more accurate representation of in vivo conditions than traditional 2D cultures. Therefore, the use of 3D culture is multidimensional and spans multiple avenues, contributing to our advancements in understanding biology, disease mechanisms, oncology research, and the development of novel therapeutic strategies.

Introns are non-coding segments within eukaryotic genes that are transcribed along with exons. They are subsequently removed during splicing, and their presence allows for generating diverse mRNA isoforms through the process called alternative splicing. The functional significance of introns going beyond mere "junk DNA" is questionable until recently; scientists identified that these pieces of junk DNA could hang around with the functional mRNA escaping splicing. Intron retention is a type of alternative splicing, a process that occurs during the maturation of messenger RNA (mRNA) in eukaryotic cells. In eukaryotes, genes typically consist of exons (coding regions) and introns (non-coding regions). After transcription, the precursor mRNA (pre-mRNA) undergoes splicing, where introns are removed, and exons are joined together to form the mature mRNA. Intron retention, however, deviates from this typical splicing process. Instead of being entirely removed from the pre-mRNA, the mature mRNA may retain one or more introns. This results in the inclusion of intronic sequences within the final mRNA transcript. The retained introns may contain premature stop codons or regulatory elements that can influence gene expression and protein function. Intron retention is a form of alternative splicing because it generates multiple mRNA isoforms from a single gene. This diversity in mRNA transcripts can produce different protein isoforms with distinct functions or regulatory properties. The regulation of intron retention is complex and involves various cellular factors, including splicing machinery components and RNA-binding proteins. Research on intron retention has revealed its importance in various biological processes, including development, cell growth and differentiation, and diseases like cancer. Aberrant intron retention has been associated with certain genetic disorders and cancers. Understanding the mechanisms and functional consequences of intron retention is crucial for unraveling the complexity of gene regulation and its impact on cellular processes. With an increasing output of data from high throughput assays line RNA Seq, scRNA-Seq, etc., it's high time data scientists look into these signatures in the context of disease pathology. This may well be the tip of the iceberg.

In the realm of molecular medicine, therapeutic small-interfering RNA (siRNA) is a promising class of molecules with exciting new opportunities in healthcare. An essential component of RNA interference (RNAi) is siRNA. In clinical setup, siRNA may be engineered to specifically target genes linked to certain diseases, providing a focused and accurate method of modulating gene expression. Many important factors characterize the use of therapeutic siRNA. Target gene expression is selectively silenced by therapeutic siRNA through the use of the RNAi pathway. Guided by corresponding messenger RNA (mRNA) sequences, the double-stranded siRNA molecule is integrated into the RNA-induced silencing complex (RISC). This mechanism causes translational repression or mRNA cleavage, which in turn causes the relevant protein to be downregulated. Therapeutic siRNA is a promising avenue in several areas. siRNA can be used in oncology to target oncogenes or other important regulators, inhibiting cancer cell proliferation. Furthermore, by modifying the expression of genes linked to disease, siRNA may be used to treat viral infections, neurological conditions, and other rare and hereditary diseases. The selectivity of therapeutic siRNA is one of its main advantages. siRNA sequences can be engineered and customized to target specific genes linked to different diseases like cancer or genetic disorders. This focused strategy improves the accuracy of the therapeutic intervention and reduces off-target effects. In a recent article by Nissen et al., siRNA targeting LP(a) in a trial with 48 participants without cardiovascular disease and with lipoprotein(a) concentrations of 75 nmol/L or greater (or ≥30 mg/dL), was used to evaluate its tolerability and efficacy to reduce LP(a). Results showed that Lepodisiran was found to be well tolerated and resulted in dose-dependent, long-lasting reduction in serum lipoprotein(a) concentrations in phase 1 trial with elevated lipoprotein(a) levels. Therapeutic siRNA-based diagnosis is rapidly advancing, and several siRNA-based medications are now entering clinical trials. These trials aim to assess the pharmacokinetics, safety, and effectiveness of siRNA therapeutics in human subjects, offering crucial new information about their potential as a treatment option. Despite the therapeutic potential of siRNA, clinical translation of siRNA faces a challenge in its effective delivery. Naked siRNA molecules are more likely to degrade with a poor half-life and poor cellular uptake. Therefore, to increase the stability and delivery of therapeutic siRNA to target cells, a variety of delivery systems, such as lipid nanoparticles, viral vectors, and polymer-based carriers, are being investigated.

Abstract Cancer stem cells (CSCs) constitute a minority cell population characterized by unbounded proliferative potential in both solid and hematological cancers. Despite sharing key stem cell attributes, CSCs possess unique traits, including the initiation and propagation of tumors and resistance to conventional therapies. The purpose of this review is to delve into the origins and fundamental characteristics of CSCs, emphasizing their role in tumor growth and metastasis. The focus extends to unraveling cellular signaling pathways driving oncogenic processes and understanding aberrant cellular crosstalk crucial for targeted cancer therapies. Beginning with an exploration of CSC properties and behavior, we progress to dissecting the cellular signaling network that fuels oncogenic pathways. The discussion spans the inception of CSCs, their survival strategies, and adaptation to new environments. We then transit to recent therapeutic advancements targeting CSCs, culminating in an exploration for precise therapeutic targeting. This review henceforth, underscores the vital significance of comprehending CSCs in cancer progression and treatment resistance. By unraveling the complex signaling pathways and survival mechanisms unique to CSCs, it paves the way for targeted therapeutic strategies that hold immense promise in enhancing cancer treatment efficacy while minimizing collateral damage.

Diet and nutrition have a tremendous influence on health and disease. Dietary constituents can affect health and have been known to supplement with essential nutrients, minerals, and calories for physiological homeostasis. However, diet can also affect gene expression through epigenetic reprogramming or by altering the level of micronutrients. While a nutrigenomics study has delineated this causal link, a recent study published in EMBO Molecular Medicine by Grant et al. went a step further to establish that maternal intake of dietary fibers can alter the fetal gut microbiome, influencing the diversity of the intestinal bacterial flora, thereby affecting the gut-brain axis. Although the relationship between diet and fertility in males and females has been reported, the effect on postnatal life is not well documented. In this study by Grant et al. at the (Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg), the authors reported that selected feeding of fiber-free diets to pregnant mice alters the gut microbiome composition of their neonate pups depriving them of protective and beneficial commensal, Akkermansia muciniphila, a mucin-foraging bacterium. Further, these animals exhibited heightened immune activity by enriching defense response pathways and IL-22 expression. Therefore, the protective role of A. muciniphila is associated with its protection against chronic inflammation through TLR4 signaling. The author’s study has far-reaching conclusions on improving human health outcomes by the rational choice of food, drugs, and lifestyle to prevent gut dysbiosis and colonization of the right microbiome.

Monobodies, as the name suggests, are the simplest synthetic version of antibodies engineered to mimic antibodies (antibody mimetics) without their complexity. These are constructed using a fibronectin type III domain (FN3) as a molecular scaffold. With a molecular mass of not more than 20 kDA at max, monobodies are excellent tools for in-vivo diagnosis. Unlike the conventional Ab that needs particular treatment protocols to enable them to enter into cells, mono, and nano bodies can be expressed inside the cells with expression cassettes. With high affinity and selectivity, mono and nanobodies can be developed in the shortest possible time with ease that otherwise can't be done by conventional antibodies. Produced from combinatorial libraries and diversified using phage display techniques, monobodies can be generated that are highly specific for their intracellular targets, like monobodies to detect COVID antigens. Similarly, monobodies against KRAS mutants using protein engineering technologies can be sued to detect mutant KRAS in solid tumors. They have a strong tendency to bind to functional sites of specific intracellular target proteins and thus exhibits drug-like properties as well as specific `inhibitors. Monobodies are evolving with additional diverse functions and may soon be used as am indispensable tool in biology and medicine.

Malaria is an endemic disease in a true sense. It is an acute febrile disease caused due to the parasite Plasmodium. However, unlike COVID-19, it failed to raise an international concern or gain the scientific limelight. Most of the 200 million globally affected by malaria, half of them are from Africa. Four of the nations, Nigeria (25%), the Democratic Republic of the Congo (11%), Mozambique (5%), and Uganda (4%), account for half of the world’s malaria burden and is the leading cause of illness and death. In 2019, an estimated 5–6 million people died of malaria – most of them are young children in sub-Saharan Africa. Many of the countries affected by malaria have the lowest economic status. In the malaria-endemic region, the most vulnerable groups are young children and pregnant women. The costs of malaria are enormous to individuals, families, communities, societies, and nations. After a struggle for three decades, the much-awaited malaria vaccine, RTS, S (brand name Mosquirix), was finally launched; but it came with its controversies and allegations. This review explored the different angles of this disease, the vaccine development, and the emerging debates.

Synthetic biology is an emerging discipline of science, at the intersection of biology, engineering, and chemistry that involves redesigning organisms to have new phenotypes and customized abilities. While synthetic biology seems to have originated from genetic engineering, over the years, it has matured as well as diverged from it. It involves not just the transfer of genes from one or cell to another creating some variants, it also involves the assembly of an altogether novel organism or cell created part by part by the assembly of individual components of the desired function in a logical fashion. In this minireview, we will explore this new discipline and its possible applications and future promises to serve the humanity

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The rising trend in obesity and overweight globally poses a serious risk for developing GDM, more among South Asian population. The occurrence of perinatal complications seems to parallel with incidence of GDM contributing significantly to adverse pregnancy outcome. The matter of fact is that diabetes just do not affect the mothers only, but also the new-born, predisposing them to various neonatal adverse outcomes, including metabolic and cardiac disorders, and respiratory distress, as wells as neurologic impairment compromising with metal development. Further, low birth weights, macrosomia, and infections are some of the most commonly occurring outcomes of GDM, the severity of which parallels with maternal blood glucose levels and age. Further, there are higher risk of hypoglycemia among the new born of hyperglycemia diabetic mothers. The numbers are soaring high, more in developing nations, with India almost topping the list with currently, over 80 million women worldwide who are affected by GDM and pregestational diabetes mellitus. How exactly GDM affects the developing fetus is still not precisely known. Animal studies using rodent models indicated glucose mediated oxidative stress, leading to excess apoptosis in the target organs as wells production of other reactive oxygen and nitrogen species. Further, an activation of unfolded protein response leading to endoplasmic reticulum stress seems to contribute to the pathogenesis of hyperglycemia. However, what is assuring is that risk mitigation against this detrimental effect can be adopted. This involves risk assessment of pregnant females at the first prenatal visit with special focus on comorbidities such as overweight with/and obesity, glycosuria, and family history and hence should be recommended for blood glucose testing (between 24 and 28 weeks of gestation). With the prevalence of GDM reported to range from 3.8% in Kashmir 17.9% in Tamil Nadu, the stakes are high. It is also clear that India has a very high prevalence of GDM by all global standards. Rational steps to tackle this problem at the early and effectively will decide its long-term consequences on maternal and child health.

Twins are a source of curiosity, both for the family and the scientific community. Genetic similarities between twins have been the preferred choice to study the heritability of traits. The fact that nature and nurture play a significant role in shaping one’s phenotype has prompted Geneticists to use twins as a proxy to address this fact. Based on the similarities, twins are of two types, monozygotic twins (MZ) and Dizygotic twins (DZ). Identical or monozygotic twins are formed when one fertilized egg (ovum), fertilized by one sperm, splits and develops into two embryos with precisely the same genetic information. The combined ratio of MZ and DZ to singleton delivery is approx 1: 100. On the other hand, fraternal or dizygotic twins are formed when two eggs (ova) are fertilized by two sperm and produce two genetically unique children in the same pregnancy. Monochorionic twins are genetically identical, sharing the same placenta. If more than two twins share the placenta, these are monochorionic multiples. Monochorionic twins occur in 0.3% of all pregnancies. Monozygotic (identical) twins share all their genes, while dizygotic (fraternal) twins only share about 50%. Hence, any similarity seen between identical twins when comparing the similarity between sets of fraternal twins for a trait or condition is most probably due to genes rather than environment. TWIN REGISTRIES Progress in twin research worldwide is carried out by establishing Twin registries or consortia based on collaborations of several twin families. These registries are a rich source of materials for Twin research. It is much needed to establish such Twin registries in India. With its 1.5 Billion population, Indian Twin registries can be a source of materials for Twin Research for the whole world.

Cancer cells are known to have an enormous appetite for calorie. This is something they are addicted to sustain their unrestricted growth and rapid proliferation. In order to accomplish this feat, cancer cells has evolved multiple mechanisms, rewiring their metabolic circuitry such that metabolic fuels are preferentially diverted to meet their energy demands. A classic example (Warburg effect) of this is aerobic glycolysis and preferential production of lactate to produce ATP (without relying on mitochondrial oxidative phosphorylation). Further, rapid proliferation of cancer cells, exhausts the nutrient and oxygen supply derived from the existing vasculature, making them hypoxic. In turn triggers the upregulation of pro angiogenic factors from the hypoxic tumor sites( HIF), which in turn re-vascularizes the tumor mass, bringing in metabolic cargo. When it comes to cancer metabolism, cancer cells are highly innovative to devise novel mechanisms to bypass metabolic regulations and In a recent article published in Nature Metabolism, Skinner et al. identified an unusual source of glucose in cancer cells. Ribose moiety of uridine can be repurposed to replenish the energy requirements in cancer cells thorough the uridine phosphorylase UPP1/UPP2 mediated cleavage of uridine into its constituents , uracil and ribose-1-phosphate (R1P). R1P is then utilized to convert into fructose-6-P and glyceraldehyde-3-P by the non-oxidative branch of the HMP shunt back to glycolysis and ATP production. These findings are novel and intuitive. It means that the cancer cells has the ability to salvage glucose from uridine, when needed. This also indicates that cutting off Uridine supply to cancer cells maybe a mechanism to target cancer cells .

With over 2.3 million new cases and 685,000 deaths, breast cancer is the most commonly diagnosed cancer worldwide, and its burden has been rising over the past decades. In India, the incidence increased significantly, almost 50%, between 1965 and 1985. As per the 2020 Globocan information, in India, BC accounted for 13.5% of all cancer cases and 10.6% of all deaths. Compared to Western countries, the poor survival of patients with breast cancer in India is due to several contributing factors such as lack of awareness, earlier onset of disease, delayed initiation and late stage of disease at presentation, and lack of consistent treatment regime. Under these circumstances, it is even more imperative to identify novel targets for breast cancer and put them to clinical use. In a recent report by Ciscar et al., the authors reported that RANK and receptor activator of NFκB ligands (RANKL) status might be important predictors in estrogen receptor (ER)-negative breast cancer. In analyses of more than 2,000 breast cancer samples, the authors confirmed that RANK expression was associated with ER− tumors, while RANKL was rarely found in tumor cells. This also let to conclude that RANK expression is an independent poor prognostic factor in breast cancer, particularly in ER− BC postmenopausal women, and is associated with poor survival. This seminal work has enormous outcomes in the clinical management of breast cancer. This also implies that RANK+ ER- breast cancer might benefit from the recently FDA-approved compound “Denosumab.” Denosumab is used to treat bone loss in men treated for prostate cancer and those who have osteoporosis. It is an inhibitor of RANKL, which is an essential factor initiating bone turnover. RANKL inhibition blocks osteoclast maturation, function, and survival, thus reducing bone resorption. The same mechanism might be beneficial in these RANK+ ER- breast cancer. Clinical trials are underway to test if denosumab can be re-purposed for this subset of breast cancer.

Humans are poor model systems for studying tissue regeneration. Unlike their amphibians or rodent counterparts, humans are deficient in this quality, making the repair process following a tissue injury infrequent and limited. Most human tissues or organs, except the liver, lack in their regenerative potential. This tends to be a serious problem in organ damage until recently with the identification of enhancer regulatory elements that engage in regenerating tissue. Tissue regeneration enhancer elements (TREEs) trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs. TREE orchestrates selective gene expression at the injury sites, thereby modulating the regenerative activities and potential of vertebrate organs. Using a genetic screen of a zebrafish-based tissue injury model, Kang et al., identified the gene expression signature associated with regeneration. This concept is being tried and tested to see its possibility in regenerating injured myocardium following myocardium infraction leading to ischemia and tissue damage. TREEs displayed specificity and efficacy in a systemically delivered recombinant AAV vector system in mice and can be used as a gene-therapy module to repair damaged tissue. A team of researchers at the Duke School of Medicine, USA, headed by Ken Poss, reported their findings in cell stem cell, 2022. These researchers further took a step ahead to actually orchestrate a damaged myocardium repair and the growth of new muscles to restore normal cardiac function. Even more spectacular is that tissue growth is selective only at injury sites and becomes quiescent once the damage is repaired. HOW THIS MAY IMPACT REGENERATIVE MEDICINE Using a TREE-based system, one can attempt to use gene therapy with viral vectors to enhance heart tissue cell proliferation and growth, thus improving cardiac regeneration. This system will further strengthen by incorporating better gene payloads, thereby opening new possibilities to rescue scar tissue and restore function. According to the World Health Organization, MI-related death in India accounts for one-fifth of deaths worldwide, which is alarmingly higher in the younger population. The age-standardized cardiovascular disease (CVD) death rate of 272/100,000 in India is much higher than the global average of 235. Under these circumstances, these findings seem extremely relevant. Although we may not fix a broken heart, engineered TREE elements might at least fix a damaged myocardium branching hopes for numerous suffering from CVD.

Cancer immunotherapy is a form of biotherapy (also called biological response modifier therapy) that refers to a broad array of anti-cancer therapies targeted to activate and trigger the body’s immune system against cancer. This includes targeted antibodies to specific cell surface entities on cancer cells, anti-cancer vaccines like vaccines against HPV in cervical cancer, cytolytic virus, adoptive cell transfer, biologicals like cytokines and other small molecular agents, and the most explored immune checkpoint inhibitors. Immunotherapies use immune modulatory materials from the same organism to fight disease, while some immunotherapy treatments use genetic engineering-based gene editing approaches to enhance the host immune system in an effort to eradicate the cancer cells and boost its cancer-fighting capabilities. Used in combination with surgery, chemotherapy, and radiotherapy, cancer immunotherapy improves their overall effectiveness. WHAT IS AN IMMUNE CHECKPOINT T cell activation involves the engagement of a number of signaling cascades, originating from the interaction between T cell receptors (TCR) with antigen-presenting cells (APC) that ultimately determine cell fate through regulating cytokine production, cell survival, proliferation, and differentiation. TCR alone is not sufficient to generate an adequate response. It needs the participation of coreceptors. Primary T cell activation involves the integration of three distinct signals (1) antigen recognition in the presence of APC, (2) costimulation, and (3) cytokine-mediated differentiation and expansion. To make sure that these activated T cells do not cross-react with self-antigens, these are rendered inactive by immune checkpoints. PDL on T cells and PDL1 on host cells engage in bringing about this. Programmed Cell Death Protein 1 (PD-1) inhibits immune responses by fostering a state of self-tolerance. This is achieved by activating apoptosis, anergy, and avoidance of antigen-specific T cells. The functional counterpart of PD-1, the Programmed Cell Death Ligand 1 (PD-L1), is a trans-membrane protein that acts as a coinhibitory immune response factor. This is what the cancer cells hijack for their survival. PD-L1 expressed on cancer cells attenuates the host T cell response transmitting negative signals. Therefore, the PD-1/PD-L1 axis is the main driver of cancer immune evasion, which needs serious attention. WHAT IS IMMUNE CHECKPOINT INHIBITORS These classes of molecules are designed to block the cross-talks between cancer cells expressing PD-L1 with T cells expressing PD-1 receptors. When the interaction is blocked, inhibitory influence on T-cells is circumvented, and an attack may be launched. Checkpoint inhibitors are used in cancer immunotherapy, including a wide range of cancers, such as melanoma, skin cancer, and lung cancer. Different drug classes block checkpoint proteins like CTLA-4 inhibitors, PD-1 inhibitors, and PD-L1 inhibitors. Commercially checkpoint inhibitors include pembrolizumab (Keytruda), ipilimumab (Yervoy), nivolumab (Opdivo), and atezolizumab (Tecentriq). RAYS OF HOPE AND CAUTION Because checkpoint inhibitors stimulate the immune system and are immunomodulatory, their usage has significantly improved cancer treatment and management, extending the life span for numerous patients. However, we need to be cautious as they may cause immune cells to attack healthy cells, causing side effects such as fatigue, nausea, high fever, flu-like symptoms, and inflammation.

Abstract Pre-eclampsia (PE) is a pregnancy-specific disorder, characterized by hypertension and proteinuria. In PE, trophoblasts mediated inadequate remodeling of uterine spiral arteries seem to interrupt uteroplacental blood flow, one of the hallmarks in the early onset of PE (EO-PE). This, in turn, results in placental ischemia–reperfusion injury during hypoxia and reoxygenation episodes, leading to the generation of reactive oxygen species (ROS) and oxidative stress (OS). But still it is debatable if OS is a cause or consequence of PE. In this present study, we have investigated the effects of OS on PE placentae and trophoblast cell functions using BeWo and HTR8/SVneo cell lines. PE placental tissues showed abnormal ultrastructure, high level of reactive oxygen species (ROS) with altered unfolded protein responses (UPR) in compare with term placental tissues. Similar to PE placentae, during OS induction, the trophoblast cells showed altered invasion and migration properties with significantly variable expression of differentiation and invasion markers, e.g., syncytin and MMPs. The effect was rescued by antioxidant, N-acetyl cysteine, thereby implying a ROS-specific effect and in the trophoblast cells, OS triggers UPR pathway through IRE1α-XBP1 axis. Taken together, these findings highlight the harmful effect of unfolded protein response, which was induced due to OS on trophoblast cells and deformed invasion and differentiation programme and can be extended further to clinical settings to identify clinically approved antioxidants during pregnancy as a therapeutic measure to reduce the onset of PE.

Most viruses–including SARS-CoV-2, seem to have evolved over time. The lack of stringent proofreading mechanisms makes viral DNA/RNA replication error-prone. When a virus replicates, it sometimes changes a little bit, which is called mutations. Any virus with one or more new mutations can be referred to as a “variant” of the original virus. The last 2 years have witnessed the emergence of a large number of variants. Since the pandemic’s beginning, the SARS-CoV-2 coronavirus has mutated extensively, resulting in the emergence of different variants of the virus. One of these is the delta variant (arising from Pango lineage B.1.617.2) that took the word in a storm this year (February-July). The current a variant of concern is the B.1.1.529 (Omicron) variant reported first from South Africa on November 24, 2021. In recent weeks, infections have been widely reported, along with the increased detection of the B.1.1.529 variant. We reviewed the emergence of the new variant (B1.1.529) and its possible outcomes.

What do scraps of bones discovered in a deserted Siberian Cave in Russia have to do with us? Or how do a few fragments of teeth in Gibraltar, an isolated British overseas territory located at the southern tip of the Iberian Peninsula, have to do with the genetic legacy of today’s living people across Asia? Well, it seems that about 40,000 years back, we humans were not the only inhabiting hominids on this planet Earth; we had other mysterious cousins, at least two of them known so far, who had left enough evidence and trails of DNA for the scientist to ponder. Like crime cases that run cold due to lack of solid evidence, paleontologists often tumble when encountering roadblocks; until Swedish Geneticists Svante Pääbo painstakingly developed the necessary tools and techniques to trace back our origin, 15000 years back when perhaps the three hominids even crisscrossed each other’s path. The Desonovians, the Nearthandals, and the modern-day humans. The two ancestors of humans perhaps arose from a common origin several thousand years back. We now know that the Desinovinans diverged from their close relatives, the Neanderthals, around 400,000 years ago, while they both diverged from modern Homo sapiens around 800,000 years ago. The Neanderthals were populated in Europe and Asia, while the more elusive Desonovians were restricted to Siberia, in regions of eastern and southern Eurasia. Genomic homology studies revealed that the Denisova’s mitochondrial DNA differs from that of modern humans by 385 bases, whereas the difference with Neanderthals is around 202 bases. These numbers stand out from the difference between chimpanzees and modern humans, approximately 1462 base pairs. It is now conclusively known that sometimes in prehistoric times, there had been an event of DNA mixing between the Denisovans and modern humans, an event of actual sexual mating. The percentage of Denisovan DNA is highest in the Melanesian population (Melanesians are the indigenous inhabitants of Melanesia, from New Guinea to the Fiji Islands), lower in other Southeast Asian and Pacific Islander populations, with hardly any DNA detectable in other populations in the world. What is enigmatic is how this human cousin got extinct. Possibly a competition for resources was likely one reason the Denisovans went extinct. The evolutionary trajectory of the Nearthandals followed a different route. At least, two different groups of Neanderthals who lived in Southern Siberia seem to have migrated from Eastern Europe. Not only that, just that Denisovans also interbred with modern-day humans. This interesting phenomenon is called Introgression. It explains why modern-day humans have some Neanderthal DNA, roughly about 3%. Human ancestors only lived in Africa until they decided to migrate to Europe some 45,000 years ago. It’s there where they encountered its other ancestors, the Neanderthals (Homo neanderthalensis). Eventually, they mated and produced offspring resulting in Introgression. Since this mating event happened outside Africa, present-day African people have no traces of Neanderthal DNA. However, due to interesting adaptive advantages, modern-day humans (outside Africa) still retained 3% of Neanderthal DNA, a spectacular observation even 40,000 years after they might have last mated. This is called adaptive Introgression. This is also where Darwin’s principles of natural selection come in. Retaining the 3% Neanderthals might serve some advantage to Modern Humans for better adaptations, something that the sickle mutated DNA at one allele (heterozygous) got positively adapted in Africa due to its protective effect against the malarial parasite in malariaendemic areas. Things can get even interesting and weird with the findings that hybrid individuals were discovered who carried both the Denisovan as well as Neanderthal DNA. That’s what the team, led by palaeogeneticists Slon et al., reported in Nature. Named as “Denny,” this child seems to be born from a Neanderthal mother and a Desinovan dad, some 90,000 years back. Denny seems to be born out of mating of two extinct hominid ancestors, acquiring one set of chromosomes from a Neanderthal and the other from a Denisovan. Shaped by evolution and driven by its migratory nature, present-day human is the cumulative outcome of thousands of years of man’s struggle for its survival. Driven by the changing environmental its migration journey picked with it traces of DNA from its ancestral cousins that it encountered. Meticulous investigation of this apparently insignificant DNA holds the secret of thousands of years of human history and human migration. Relentless efforts by Prof Svante Pääbo and other researchers have shed light on our ancestral autobiography.

Cancer stem cells (CSC) are the minor population of cancer originating cells that have the capacity of self-renewal, differentiation, and tumorigenicity (when transplanted into an immunocompromised animal). These low-copy number cell populations are believed to be resistant to conventional chemo and radiotherapy. It was reported that metabolic adaptation of these elusive cell populations is to a large extent responsible for their survival and distant metastasis. Warburg effect is a hallmark of most cancer in which the cancer cells prefer to metabolize glucose anaerobically, even under normoxic conditions. Warburg’s aerobic glycolysis produces ATP efficiently promoting cell proliferation by reprogramming metabolism to increase glucose uptake and stimulating lactate production. This metabolic adaptation also seems to contribute to chemoresistance and immune evasion, a prerequisite for cancer cell survival and proliferation. Though we know a lot about metabolic fine-tuning in cancer, what is still in shadow is the identity of upstream regulators that orchestrates this process. Epigenetic modification of key metabolic enzymes seems to play a decisive role in this. By altering the metabolic flux, cancer cells polarize the biochemical reactions to selectively generate “onco-metabolites” that provide an added advantage for cell proliferation and survival. In this review, we explored the metabolic-epigenetic circuity in relation to cancer growth and proliferation and establish the fact how cancer cells may be addicted to specific metabolic pathways to meet their needs. Interestingly, even the immune system is re-calibrated to adapt to this altered scenario. Knowing the details is crucial for selective targeting of cancer stem cells by choking the rate-limiting stems and crucial branch points, preventing the formation of onco-metabolites.

COVID-19 pandemic caused due to SARS-CoV2 has disrupted the spectrum of health care. The wide arrays of supportive and palliative care needed for patients with ailments were grossly neglected, due to the diversion of resources and healthcare professionals in COVID management. This deficiency was further exaggerated by extended lockdown and closure of outdoor patient care services resulting in unprecedented crisis in disease management. Further, COVID-19 has been associated with increased risk of morbidity and mortality arising from associated risk factors in geriatric subjects and those with other high risk co-morbidities like hypertension, COPD, diabetes and cancer. North East Indian states and the adjoining regions seem to have suffered substantially during the COVID-19 crisis due to their pre-existing vulnerabilities and under developed health care infrastructure and logistics. This deficiency, however, seems to have been fulfilled substantially by the participation of NGO (Non-Government Organizations) and other volunteer services who has actively participated to provide basic healthcare and other life support to cancer patients in this crisis.

BACKGROUND: Breast cancer (BC) has been the most frequently diagnosed cancer among women and it has multiple risk factors. Epstein–Barr virus (EBV) has been shown to be associated with BC as one of the risk factors. Our aim was to detect EBV DNA in blood samples of BC patients of North-East India. MATERIALS AND METHODS: A total of 53 eligible BC patients' samples were analyzed by Nested polymerase chain reaction for EBV Antigen-1 (EBNA1) gene. All statistical analysis was carried out using the software of statistical package for social sciences (SPSS) version 21. RESULTS: 20.8% (11 of 53) BC patients' blood samples have EBNA1 gene DNA. The median age of BC patients was 42 and 43 years for EBV-positive and EBV-negative groups. 96.22% EBV-positive BC patients were diagnosed with high-grade malignancy. 54.54% of EBV-positive BC patients were diagnosed with T3 and T4 stage cancer. EBV-positive patients have not shown statistically significant association with ER positive (P-0.877, odds ratio [OR]: 1.111), PR positive (P-0.256, OR-2.16), Her-2/neu positive (P-0.93, OR-1.017), Ki-67 positive (P-0.487, OR: 1.8), and AR positive (p-1.000, OR-0.836). CONCLUSION: We conclude from our study that EBNA1 gene was found in the blood samples of subset of BC patients of North-East India. Further studies with BC tissue and adjacent normal tissue samples of BC patients will be required to provide evidence about EBV's role with BC of North-East India.

Background: Stroke is the second leading cause of death globally and it is a major cause of long-term, physical, psychological, and social disability among the elderly. Increasing evidence shows that ischemic injury and inflammation account for its pathogenic progression. So, we studied the association of Intercellular Adhesion Molecule 1 (ICAM1) polymorphism with ischemic stroke, stroke severity, and outcome. Aims and Objectives: To compare ICAM1 469 E/K polymorphism in ischemic stroke patients with healthy controls, and to study its association with stroke severity and outcome. Materials and Methods: Fifty patients of ischemic stroke and hundred healthy individuals were included. The stroke severity was assessed clinically and radiologically. Outcome was measured at three and six months of stroke onset. Genomic DNA was used for Allele-Specific PCR to detect ICAM1 469 E/K polymorphism. The subjects were categorized into EE, EK, and KK genotypes. Results: The odds of EK genotype to develop stroke was 0.41 (95 % CI; 0.17 - 0.92) (p = 0.07) and of KK genotype was 0.41 (95 % CI; 0.11 - 0.87) (p = 0.04) compared to EE genotype. Subjects with ICAM1K allele had significantly reduced risk of stroke compared with those with E allele. (RR: 0.55; 95% CI: 0.35-0.87) (p=0.03). Conclusion: Subjects with ICAM1K allele had significantly reduced the risk of developing stroke. 469 E/K polymorphism of the ICAM1 gene does not significantly affect stroke severity, mortality, and outcome.

Artificial intelligence (AI) is a rapidly expanding avenue in science and is often used to describe the use of computers, big data mining, modeling, and network that may simulate intelligent behavior and critical thinking similar to a human being but at an exceedingly fast pace. What lies at the heart of AI are intelligent algorithms that drive the whole process integratively, imparting the decisive ability to machines. The artificial intelligence market is expected to grow at a rate of 39.4% by 2022-2028. British mathematician Alan Turing’s 1950 paper “Computing Machinery and Intelligence " established AI's fundamental goal and vision. Fundamentally, AI is a branch of computer science that aims to answer Turing’s question of replicating human intelligence as machines. Since AI research aims to make smarter algorithms evolve and emulate human-like functioning, the degree to which an AI system can replicate human capabilities is used to determine the types of AI. The volume, magnitude, and complexity of data in healthcare mean that artificial intelligence (AI) will be increasingly applied and exploited, with several types of AI already being employed by researchers, clinicians, and data analysts. AI is a collective term, not just one technology, with an immediate relevance to healthcare. Few AI technologies of high importance to healthcare are: Machine learning, Neural Networks, and Deep Learning Natural Language Processing ( NLP) Physical Robots Rule-based expert systems The AI-associated healthcare market is growing at an exponential pace and is expected to reach USD 6.6 billion by 2021. Precision medicine initiatives can be divided into three types of clinical areas: complex algorithms, digital health applications, and “omics”-based tests. Large genomic datasets and informatics related to demographic data or diagnostic reports are exploited by machine learning algorithms for prediction and prognosis. This is coupled with patient healthcare data, such as treatment protocols, treatment response, response to therapy, and health monitoring, with data input from clinicians, researchers, and the public domain. High throughput big data from population-based studies are used with machine learning algorithms to establish correlations, build predictive models, and provide customized treatment protocols. In Omics based era, data from genomics, proteomics, and metabolomics are exceedingly used to address and identify health-related problems in large study cohorts . This will provide opportunities for translation and transition from bench to bedside through precision medicine.

Neglected tropical diseases (NTDs) are those that are commonly found in several low-income countries in Africa, Asia, and Latin America and where people do not have access to hygiene, clean water, or safe ways to dispose of human waste. NTDs comprise a diverse group of diseases that is highly prevalent in tropical countries and is caused by a variety of pathogens, including bacteria viruses, parasites, and fungi. Although there are debates on what is included under NTD, few that are listed are ascariasis, Buruli ulcer, Chagas disease, dracunculiasis, hookworm infection, human African trypanosomiasis, Leishmaniasis, leprosy, lymphatic filariasis (LF), onchocerciasis, schistosomiasis, trachoma, and trichuriasis, though this list. keeps on changing. They are called “neglected,” because they are hardly represented in the global health agenda of the developed countries and are often associated with stigma, blind faith, and social exclusion. The epidemiology of NTDs is quite complex and often related to environmental conditions. Many of them are vector-borne, have a zoonotic origin with well characterized animal reservoirs, and are associated with complex life cycles. All these factors make their public health control challenging. With a population of over 1.3 billion, India accounts for nearly one-half of the world’s prevalent cases of visceral leishmaniasis and one-half of the global incident cases of dengue, one-third, or more of the prevalent cases of leprosy, LF, cysticercosis, and visual impairment due to trachoma. India also accounts for 25% world’s burden of ascariasis and hookworm cases. Unfortunately in India, we don’t have a uniform distribution of neglected diseases. It was found to be very much dependent on the geographical locations as well as biased on the socialeconomic status, with more prevelant amongst the lower income groups. NTDs are not just any regular disease but were reported to cause permanent disabilities, impacting mental health and thereby posing a serious threat to livelihood and standard of living. Challenges in studying NTD The primary challenge is adequate research funding and efforts. Affecting emerging economies, NTD severely suffers from the limelight that other lifestyle diseases such as cardiovascular, diabetes, and oncology enjoys. There was not much research output from the Western world too as NTD mostly affects the poorer nations. NTD related technologies are not considered profitable. This trend is slowly changing with larger participation from the government to aid in NTD research. We hope that future days will show more effort and awareness toward a better solution.

COVID-19 pandemic has far-reaching consequences on people with comorbidities like Diabetes Mellitus (DM), asthma, cardiovascular disease, and cancer. What seems unusual is an isolated observation that emerged from several independent studies worldwide. Postmenopausal females seem to suffer from severe COVID symptoms. Few of them also show an extended COVID symptom, also “LONG COVID.” Though the association appears strong, there are not enough credible studies to pin it down to the exact cause. We explored the possibility to see if postmenopausal females are at a higher risk for severe COVID and unravel this observation’s molecular pathogenesis. Research performed at King’s College London found that as estrogen levels in females drop in pre-menopause and menopause, they become vulnerable to COVID19 infection, suggesting that high estrogen levels may have a protective effect against the severity of COVID-19. This concept originated from the immune-modulatory and immune suppressive role of estradiol. Although both male and female sex steroids act primarily on the reproductive tissues and modulate their functions, increasing evidence suggests that sex steroids can also work on non-reproductive tissues like the CNS, immune systems, cardiovascular and skeletal systems, etc. Further, estrogen has an enormous effect both on the innate (macrophages/monocytes, neutrophils, NK cells, complement systems, APC-like dendritic cells (DC)], as well as on the adaptive (B and T cells) immune system. There are reports that estrogen may exhibit a pro-inflammatory response, whereas testosterone counteracts it. This could possibly be through an estrogen-mediated production of inflammatory cytokines like IFNγ, interleukin (IL) 6, TNF α. However, estrogen also has a profound anti-inflammatory effect. We need to remember that many of these observations are context and cell-type-specific with a delicate balance between pro and anti-inflammatory responses. There needs a deeper understanding of the reproductive events in females. Perimenopause, menopause, and postmenopause define the end of a woman’s reproductive years. These are the time when her monthly period stops. Whole perimenopause marks the beginning of this process, starting 8- 12 years before menopause. Menopause is the stage when her menstrual periods completely ceases for at least 12 months. Postmenopause is the stage after menopause that continues thereafter. Starting from perimenopause, menopause is marked by declining levels of estrogen((estrone (E1), 17β-estradiol (E2), estriol (E3)), and progesterone. However, there are complex hormonal and cytokine undercurrents to this rather simplistic profile. LH and FSH, however, seem to surge during this period. It currently not know what this LH/FSH surge means for the immune system. With the approach of menopause, there is the release of extracellular vesicles containing inflammasomes, which may be responsible for low-grade systemic inflammation.This cascade may build up significantly and contribute to a hyper-inflammatory environment. According to a survey by Global Health 50/50, though an equal number of males and females were tested positive for COVID-19, the males were largely presented with severe symptoms, thereby implying that the female hormones may have a protective role in the pathophysiology of COVID-19. Further clinical studies performed on the females showed that pre-menopausal females have a relatively mild disease, while menopausal females had moderate to severe illness. The menopausal group also has significantly more requirements for oxygen, ventilation support, and progression-to-severe disease with a prolonged hospital stay and mortality. This is further reinforced by the fact that estradiol modulates the immune cells, which could play an essential role in explaining why a lower incidence of COVID-19 is observed among women than in men. Even been a nuclear hormone, estrogen has cytoplasmic targets. The cytoplasmic activity of estrogen-activated ERα leads to PI3K induction. This, in turn, prevents the nuclear shuttling and transport of NF Menopause kB, resulting in reduced inflammation. The estrogen axis for inflammation is enormously complex, riddled by the different receptor types usage and post-receptor events. The presence of estrogen receptors (ESRs), ERα and ERβ, is of prime importance since the net outcome depends on ER subtypes in use. It seems that a preferential engagement of ERbeta promotes inflammation while ERalpha dampens it. It was further demonstrated that hypoxia, associated with inflammatory conditions, could also downregulate the expression of ERα, tipping the balance in favor of inflammation. Then there are interferon genes that cross talks with Estrogen receptor (ESR) signaling. Estrogen can also polarize toward a TH2 response eliciting a protective humoral response in addition to its capacity for activation of NK cells. Further, a wide variety of immune-modulatory roles is under estrogenic control. This involves the antigen-presenting dendritic cells, CD4+ and CD8+ T cell populations. Other than estrogen, progesterone also has a profound influence on the immune system. Progesterone was found to have an antiviral effect against SARS-CoV-2 in vitro. Mature NK CD56dimCD16+KIR+ cells overexpress the progesterone receptor and thus are hormone-sensitive. Though there are conflicting reports regarding the association of disease severity and mortality with estrogen levels, it is plausible that drastic alteration of these hormones at menopause could perturb the delicate balance creating an environment that enhances the immune response fueling the cytokine storm, the hallmark for COVID complications. Further research in this area is needed to decipher the intricate molecular details of this process for future risk mitigation and disease management.

COVD-19 caused due to SARS-CoV2, family of Coronaviridae, the order Nidovirales, and the genus Coronavirus. A zoonotic spillover infection from bats to humans through some intermediate host was proposed to be responsible for its origin. This theory gained traction and raised no concern because our experience with other pathogenic viruses with humans in the past followed a similar trajectory. However, what caught the attention are few missing pieces of the jigsaw puzzle that seems to defy logic. A detailed investigation revealed a trail of deception, negligence, and blotched attempt of cover-up.

COVID-19 is a pandemic of disproportionate magnitude. Its devastating effect seems to have a more significant impact on the emerging economies like India and the rest of SE Asia, which also has regions harbouring some of the world's highest population density living under poor socio-economic condition. What seems to have originated from one just one province in China, rapidly speard like wildfire across international territories, affecting millions and crippling the health care system. After about eight months into COVID-19, we realized that the fallout is not only humongous but also stretched across multiple avenues of the society and different aspects of our life. The scars of COVID-19 are much more than the virus itself. With a global shutdown in business and financial institutions, the economy is in free fall. Markets plummeted, stocks crashed and unemployment numbers skyrocketed. Apart from the economy, COVID-19 related shutdown has a tremendous impact on the healthcare system for those with preventable ailments, which were either compromised or delayed affecting millions who need hospitalization for non-COVID causes. COVID crisis also seems responsible for the emergence of a new culture system and mindset that was unprecedented before. With schools and other academic institutions closed, online teaching through electronic media and work from home became the new normal. In this editorial, we summarized the collateral damage on society, economy, and human health in the COVID crisis and few suggestions to chalk out a new plan and strategy to address the challenges for a future episode of similar nature. Though we could still remain vulnerable against similar contagious agents, an advanced planning strategy and preparedness will surely help us better in effective damage control and risk mitigation, not only to reduce mortality, but also from economic downfall.

Implantation in humans is a multistep process that involves apposition, adhesion, and invasion of the developing blastocyst into the receptive maternal endometrium. Though significant volume of research in this direction has identified important players orchestrating this delicate process, there are still gaps in our understanding of all the sequence of events during embryo implantation. Also, the early pregnancy-related complications that lead to fetal loss and miscarriage often occur in this critical window of implantation, which is primarily defined as the time when the maternal endometrium is supposed to be most receptive to the free blastocyst that emerges out from the zona pellucida. Studies in humans and rodents have identified several mediators like folliculin, LIF, IL11Rα, splicing factor SC35, etc. to be essential for early implantation. Trophoblasts, that form the outer epithelial layer of the blastocyst, participate in the formation of the placenta. During placentation, invasive extravillous trophoblasts (EVTs), migrate into the endometrium, and a transient epithelial to mesenchymal transition (EMT) and remodel the uterine arteries for blood and nutrient exchange.

The overproduction of reactive oxygen species (ROS) has been associated with various human diseases. ROS exert a multitude of biological effects with both physiological and pathological consequences. Monosodium glutamate (MSG), a sodium salt of the natural amino acid glutamate, is a flavor-enhancing food additive, which is widely used in Asian cuisine and is an ingredient that brings out the “umami” meat flavor. MSG consumption in rats is associated with ROS generation. Owing to its consumption as part of the fast-food culture and concerns about its possible effects on pregnancy, we aimed to study the impact of MSG on placental trophoblast cells. MSG exposure influenced trophoblast invasion and differentiation, two of the most critical functions during placentation through enhanced production of ROS. Similar findings were also observed on MSG-treated placental explants, as confirmed by elevated Nrf2 levels. Ultrastructural studies revealed signs of subcellular injury by MSG exposure. Mechanistically, MSG-induced oxidative stress with endoplasmic reticulum stress pathways involving Xbp1s and IRE1α was observed. The effect of MSG through an increased ROS production indicates that its long-term exposure might have adverse health effect by compromising key trophoblast functions.

Publish or perish has been the mantra for researchers and scientists. It is an aphorism describing the sheer pressure to publish academic work in order to succeed in an academic career. After all what good one has done if they didn’t even publish an article in a good journal. A good journal is the one with the highest impact factor. The Impact Factor is calculated by dividing the number of citations in the JCR year by the total number of articles published in the two previous years. An Impact Factor of 1.0 means that, on average, the articles published 1 or 2 years ago have been cited one time. While the impact factor metric is very unreliable to judge the quality of the journal or published paper, as numerous unfair and dubious means were frequently adopted to boost the journal impact factors. But still, the race is on with the psychology to publish in higher impact journals as it is often associated with greater academic rewards. What emerged out of this race is that journals and the publishing houses ramped the article processing charges (APC) to an astronomical level, which was unprecedented before. APC for a few BMC, MDPI, SAGE DOVE press journals on an average exceed 2000 USD, equivalent to few months salary of the Principle Investigtor. Journal publishing house often justifies high APC citing reasons for “open access” such that they are freely available for a wider range of readers free of cost or to meet their operational cost. Although apparently sound like a great initiative, a little more investigation reveals an underlying agenda, which is far from true when we find that a majority of this same. Publishing house ferociously opposes Sci-hub like 3d party platforms which genuinely gives free access to all readers worldwide. Recently, three major academic publishers Elsevier, Wiley, and American Chemical Society filed a copyright infringement suit in the Delhi High Court, India against “Sci-Hub” and “Libgen” which provide free access to millions of research papers/books. This clearly indicates that their intentions are misaligned with what they say. High APC is a means to just earn larger profit margins. Publishing house does mention a fee waiver for low-income countries but is exploited and abused instead of this as a helping gesture. Scientific research can hardly proceed in solo. It needs infrastructure, trained manpower, logistic support, and high-level coordination. Providing fee waivers for publication to countries that hardly can feed its starving populations makes little sense because either way, these countries are far behind to have material to publish or to engage in any credible research. Instead what is happening is what is called “author swapping” wherein the corresponding or co-corresponding authors are cherry-picked from these improvised nations for APC waiver without them anyway participating in the scientific study. This is surely unethical. Journals are also reported extorting authors who fail to pay the APC. There are other flip sides of APC. High APC skew only those rich and affluent labs/groups who may be able to afford them, something getting away even with mediocre articles while genuine data from less affluent labs may never be able to reach these journals. This trend is growing alarmingly high, filtering out publications only from wealthy labs. Though the scientific community is well aware of this, very little is actually done to prevent this as the nexus runs deep benefiting few who can afford it. Unless this chain is broken, future science may just be determined by those who can afford the high APC to get into the highest impact journals, and not by the quality of science.

Rapidly spreading Omicron (B1.1.529) poses a considerable health risk, despite being labeled as a mild SARS-CoV2 variant. The higher transmissibility, immune evasion properties along blunting the effect of vaccine are some of its unique features, a fact that should not be ignored, no matter how benign it might be. We suggest that our knowledge and experience in dealing with Omicron have been very less and its long-term health consequences are still not studied properly. Under these conditions, we must continue to remain vigilant following all safety measures and avoid down-sizing its impact.

It has been 2 years plus that the global pandemic has shadowed every aspect of human life. We have witnessed multiple waves of invasion by the different mutated versions of SARS-CoV-2, with each wave specific predominant symptoms and casualties. At present, we are witnessing the rage of Omicron, another mutated version of the virus, carrying 32 alterations in its spike proteins. What makes Omicron unique is its extremely high transmissibility, spreading like wildfire across the globe, with its footprints in over 90 countries infecting over several million. The high mutational burden of Omicron is perhaps the outcome of the selection pressure that this virus has been encountering while infecting its hosts. Added to that is also the effect of vaccination contributing to the emergence of different variants. What is spectacular is that Omicron is relatively less lethal than the previous variants though it contains many more alterations. This may be pointing toward a scenario of mutational exhaustion as well the status of an enhanced host immune surveillance. Under these conditions, it is conceivable that the virus will run out of all its maximal capacity to mutate. We must accept the fact that the virus and its variants will keep on coming and time and often they might take an upper hand but over years, we will get used to this and learn ways to coexist. We must adjust our vaccine development pipelines and other risk mitigation tools to evade the risk. This has been the case with the influenza virus and it is likely that SARS-CoV-2 will follow the same. Let’s look at the other examples of this kind. How did other pandemics that affect humankind before has ended? The viruses did not go away completely, the modern H1N1, a descendent of the Spanish flu virus, circulates as H3N2 even today. Humans did not completely develop a herd immunity and knocked it off. That simply did not happen. Rather, the viruses became endemic and we will learn to live together. Both sides will develop safety nets so that none affects the other beyond a point of mutual coexistence. A better infectious agent evolves to ensure the survival of its host so that it can sustain itself without killing it. SARS-CoV-2 seems getting educated along these lines too. SARS-CoV-2 evolution to Omicron is perhaps a step in that direction.

Cell to Cell communications is the pivot for life processes. Any event that disrupts this leads to the loss of physiological function, eventually leading to cell death. Evolutionarily, cells developed an elaborate mechanism to undertake this paramount responsibility through cell surface glycocalyx, receptors, integrins, and other recognition molecules. Cells also exchange through local acting soluble mediators as well as through vesicles and exosomes. Recent development in this field led to the identification of a spectacular network of membrane process that seems to be the supremo of all that was known about cellular communications. These are called membrane nanotubes or tunneling nanotubes (TNT). Cellular communication can be subdivided into contact and contactless. The former provides more rapid and molecule transfer as compared to the latter. Tunneling nanotubes (TNTs) are a novel type of contact-based communication. TNTs are straight, thin membrane extensions connecting cells over long distances first reported in PC12 cells in 2004. TNT is believed to form from actin-based membrane protrusion. There are three different models of TNT formation. a>Protrusions from one cell grow and extend until it reaches the other cell, followed by a membrane fusion. b> Membrane protrusions grow from both cells until they meet and establish a connection c> TNT formation by cell dislodgement when cells migrate further apart from each other, and during this movement, TNT is formed. It is possible that all these three models may be operational depending on cell types and context. Tunneling nanotubes (TNT) are dynamic connections between cells, representing a novel route for cell-to-cell communication. TNT was reported in various cell types, like epithelial cells, neuronal cells, mesenchyma cells, and immune cells engaged in intercellular exchanges of molecules, subcellular organelles, and pathogen and viruses transport routes. TNT can extend up to 200 µm in length and about 50 nm to 1500 nm in diameter in macrophages. TNT can be established between similar cell types (homo-TNT) or between one cell type and another ( hetro TNT) and thus may be involved in the initiation and growth of cancer as well as dissemination of cancer cells. TNTs are also assumed to play a role in treatment resistance, e.g., in chemotherapy treatment of cancer. Recently, TNT has been used to hijack mitochondria from healthy cells by the cancer cells as a source of energy. TNT was also reported to transport miRNA and other RNA to the surrounding stroma creating an environment suitable for cancer growth. More research in this discipline is needed to understand the full function of these wonderful nanostructures.

Pregnancy in humans is a multi-step complex physiological process comprising three discrete events, decidualization, implantation and placentation. Its overall success depends on the incremental advantage that each of the preceding stages passes on to the next. The success of these synchronized sequels of events is an outcome of timely coordination between them. The pregnancy events are coordinated and governed primarily by the ovarian steroid hormones, estrogen and progesterone, which are essentially ligand-activated transcription factors. It’s well known that intercellular signaling of steroid hormones engages a plethora of adapter proteins that participate in executing the biological functions. This involves binding of the hormone receptor complex to the DNA response elements in a sequence specific manner. Working with Drosophila melanogaster, the heat shock proteins (HSPs) were originally described by Ferruccio Ritossa back in the early 1960s. Over the years, there has been considerable advancement of our understanding of these conserved families of proteins, particularly in pregnancy. Accumulating evidence suggests that endometrial and uterine cells have an abundance of HSP27, HSP60, HSP70 and HSP90, implying their possible involvement during the pregnancy process. HSPs have been found to be associated with decidualization, implantation and placentation, with their dysregulation associated with implantation failure, pregnancy loss and other feto-maternal complications. Furthermore, HSP is also associated with stress response, specifically in modulating the ER stress, a critical determinant for reproductive success. Recent advances suggest a therapeutic role of HSPs proteins in improving the pregnancy outcome. In this review, we summarized our latest understanding of the role of different members of the HSP families during pregnancy and associated complications based on experimental and clinical evidences, thereby redefining and exploring their novel function with new perspective, beyond their prototype role as molecular chaperones.