Prevalence of hemoglobinopathies among Malayali tribes of Jawadhu hills, Tiruvannamalai district, Tamil Nadu, India: a community-based cross-sectional study.

BACKGROUND: Hemoglobin (Hb), a red pigment of red blood cells (RBCs), carries oxygen from the lungs to different organs of the body and transports carbon dioxide back to the lungs. Any fault present in the Hb structure leads to undesirable functional effects of the RBCs, such as sickle cell anemia (SCA), thalassemia, etc. Hemoglobinopathies affect around 7% of people in both developed and developing countries globally. The aim of the present study was to determine the prevalence and carrier frequencies of hemoglobinopathies including SCA, thalassemia, and other abnormal Hb variants among Malayali tribes in the Jawadhu hills of Tiruvannamalai district, Tamil Nadu, India. METHODS: A community-based cross-sectional study was carried out among 443 Malayali tribes inhabiting the Jawadhu hills of Tiruvannamalai district from July 2022 to September 2022. The RBC indices were analyzed using an automated 5-part hematology analyzer (Mindray, BC-5150) and hemoglobin fractions were done using the HPLC system (Bio-Rad, D-10) following standard protocols. FINDINGS: A total of 443 participants were screened, out of whom 14.67% had an abnormal Hb fraction, 83.30% were identified as normal, and 2.03% were borderline. Notably, the study revealed a prevalence of 0.68% for the α-thalassemia trait and 13.99% for the ß-thalassemia trait. INTERPRETATION: Haemoglobinopathies, specifically the ß-thalassemia trait, were most prevalent among the Malayali tribal population of Tamil Nadu residing in the Jawadhu hills of Tiruvannamalai district. Hence, we need special attention for creating awareness, increasing hemoglobinopathies screening programs, and improving the importance of tribal health conditions by the government and non-governmental organizations (NGOs) for the betterment of the ethnic tribes.

Genome sequence of pan drug-resistant enteroaggregative Escherichia coli belonging to ST38 clone from India, an emerging EAEC/UPEC hybrid pathotype.

Here, we report the genomic characterization of a pan drug-resistant (PDR) enteroaggregative Escherichia coli (EAEC) isolated from an immunocompromised infant who had diarrhea. The isolate belonged to the sequence type (ST) 38, which is a known enteroaggregative Escherichia coli (EAEC)/uropathogenic Escherichia coli (UPEC) hybrid strain having multi-drug resistance (MDR). The strain carried genes encoding multiple resistances to carbapenems, third-generation cephalosporins, polymyxin, fluoroquinolones, aminoglycosides, fosfomycin, nitrofurantoin, sulphonamides, and multiple efflux pump genes. Interspecies horizontal transfer, inter-strain, and clonal spread of these resistances to commensals and pathogens will be worrisome. We are concerned about the spread of such PDR strains. The genomic characterization of such strains will be useful in understanding the genetic makeup of EAEC/UPEC hybrid strains and developing new vaccines/diagnostics and therapeutics.

Challenges and opportunities for cancer stem cell-targeted immunotherapies include immune checkpoint inhibitor, cancer stem cell-dendritic cell vaccine, chimeric antigen receptor immune cells, and modified exosomes.

Cancer stem cells (CSCs) are associated with the tumor microenvironment (TME). CSCs induce tumorigenesis, tumor recurrence and progression, and resistance to standard therapies. Indeed, CSCs pose an increasing challenge to current cancer therapy due to their stemness or self-renewal properties. The molecular and cellular interactions between heterogeneous CSCs and surrounding TME components and tumor-supporting immune cells show synergistic effects toward treatment failure. In the immunosuppressive TME, CSCs express various immunoregulatory proteins, growth factors, metabolites and cytokines, and also produce exosomes, a type of extracellular vesicles, to protect themselves from host immune surveillance. Among these, the identification and application of CSC-derived exosomes could be considered for the development of therapeutic approaches to eliminate CSCs or cancer, in addition to targeting the modulators that remodel the composition of the TME, as reviewed in this study. Here, we introduce the role of CSCs and how their interaction with TME complicates immunotherapies, and then present the CSC-based immunotherapy and the limitation of these therapies. We describe the biology and role of tumor/CSC-derived exosomes that induce immune suppression in the TME, and finally, introduce their potentials for the development of CSC-based targeted immunotherapy in the future.

Umbilical Endometriosis in a Surgically Naïve Multiparous Young Female.

The existence of functional endometrial tissue outside the uterus is known as endometriosis. It is a benign estrogen-dependent gynecological condition that affects 5%-10% of women who are of reproductive age. Endometriosis often affects the ovary and fallopian tubes, although it can also occur in nonpelvic areas. The most typical location for extra-pelvic endometriosis is the abdomen. Umbilical endometriosis is a rare condition accounting for 0.5%-1.0% of all cases of endometriosis. In 3% of cases, there is a chance of malignant change. This disorder's precise etiology is uncertain. Recurrent discomfort and swelling around the umbilicus are the classic manifestations. In this instance, we describe a patient with primary umbilical endometriosis (PUE) who had cyclical bleeding and swelling over the umbilicus and was surgically naive. This case will demonstrate how, particularly in surgically naïve instances, diagnosis of PUE is frequently delayed due to ignorance of the entity.

A comprehensive insight into the immunomodulatory role of MSCs-derived exosomes (MSC-Exos) through modulating pattern-recognition receptors (PRRs).

Mesenchymal stem cell-derived exosomes (MSC-Exos) are emerging as remarkable agents in the field of immunomodulation with vast potential for diagnosing and treating various diseases, including cancer and autoimmune disorders. These tiny vesicles are laden with a diverse cargo encompassing proteins, nucleic acids, lipids, and bioactive molecules, offering a wealth of biomarkers and therapeutic options. MSC-Exos exhibit their immunomodulatory prowess by skillfully regulating pattern-recognition receptors (PRRs). They conduct a symphony of immunological responses, modulating B-cell activities, polarizing macrophages toward anti-inflammatory phenotypes, and fine-tuning T-cell activity. These interactions have profound implications for precision medicine, cancer immunotherapy, autoimmune disease management, biomarker discovery, and regulatory approvals. MSC-Exos promises to usher in a new era of tailored therapies, personalized diagnostics, and more effective treatments for various medical conditions. As research advances, their transformative potential in healthcare becomes increasingly evident.

HOXA9 versus HOXB9; particular focus on their controversial role in tumor pathogenesis.

The Homeobox (HOX) gene family is essential to regulating cellular processes because it maintains the exact coordination required for tissue homeostasis, cellular differentiation, and embryonic development. The most distinctive feature of this class of genes is the presence of the highly conserved DNA region known as the homeobox, which is essential for controlling their regulatory activities. Important players in the intricate process of genetic regulation are the HOX genes. Many diseases, especially in the area of cancer, are linked to their aberrant functioning. Due to their distinctive functions in biomedical research-particularly in the complex process of tumor advancement-HOXA9 and HOXB9 have drawn particular attention. HOXA9 and HOXB9 are more significant than what is usually connected with HOX genes since they have roles in the intricate field of cancer and beyond embryonic processes. The framework for a focused study of the different effects of HOXA9 and HOXB9 in the context of tumor biology is established in this study.

Molecular Mechanisms of Tumorgenesis and Metastasis of Long Non-coding RNA (lncRNA) NEAT1 in Human Solid Tumors; An Update.

The expression of the nuclear paraspeckle assembly transcript 1 (NEAT1), as a well-known long non-coding RNA (lncRNA), is often upregulated in varied types of cancers and associated with poor survival outcomes in patients suffering from tumors. NEAT1 promotes the tumors growth by influencing the various genes' expression profile that regulate various aspects of tumor cell behavior, in particular tumor growth, metastasis and drug resistance. This suggests that NEAT1 are capable of serving as a new diagnostic biomarker and target for therapeutic intervention. Through interrelation with enhancer of zeste homolog 2 (EZH2), NEAT1 acts as a scaffold RNA molecule, and thus regulating the expression EZH2-associated genes. Additionally, by perform as miRNA sponge, it constrains suppressing the interactions between miRNAs-mediated degradation of target mRNAs. In light of this, NEAT1 inhibition by small interfering RNA (siRNA) hampers tumorgenesis. We summarize recent findings about the expression, biological functions, and regulatory process of NEAT1 in human tumors. It specifically emphasizes the clinical significance of NEAT1 as a novel diagnostic biomarker and a promising therapeutic mark for many types of cancers.

High-resolution cell imaging using white light phase shifting interferometry and iterative phase deconvolution.

An optimization algorithm is presented for the deconvolution of a complex field to improve the resolution and accuracy of quantitative phase imaging (QPI). A high-resolution phase map can be recovered by solving a constrained optimization problem of deconvolution using a complex gradient operator. The method is demonstrated on phase measurements of samples using a white light based phase shifting interferometry (WLPSI) method. The application of the algorithm on real and simulated objects shows a significant resolution and contrast improvement. Experiments performed on Escherichia coli bacterium have revealed its sub-cellular structures that were not visible in the raw WLPSI images obtained using a five phase shifting method. These features can give valuable insights into the structures and functioning of biological cells. The algorithm is simple in implementation and can be incorporated into other QPI modalities .

A Magnesium Binding Site And The Anomeric Effect Regulate The Abiotic Redox Chemistry Of Nicotinamide Nucleotides.

Nicotinamide adenine dinucleotide (NAD+) is a redox active molecule that is universally found in biology. Despite the importance and simplicity of this molecule, few reports exist that investigate which molecular features are important for the activity of this ribodinucleotide. By exploiting the nonenzymatic reduction and oxidation of NAD+ by pyruvate and methylene blue, respectively, we were able to identify key molecular features necessary for the intrinsic activity of NAD+ through kinetic analysis. Such features may explain how NAD+ could have been selected early during the emergence of life. Simpler molecules, such as nicotinamide, that lack an anomeric carbon are incapable of accepting electrons from pyruvate. The phosphate moiety inhibits activity in the absence of metal ions but facilitates activity at physiological pH and model prebiotic conditions by recruiting catalytic Mg2+. Reduction proceeds through consecutive single electron transfer events. Of the derivatives tested, including nicotinamide mononucleotide, nicotinamide riboside, 3-(aminocarbonyl)-1-(2,3-dihydroxypropyl)pyridinium, 1-methylnicotinamide, and nicotinamide, only NAD+ and nicotinamide mononucleotide would be capable of efficiently accepting and donating electrons from and to pyruvate within a nonenzymatic electron transport chain. The data are consistent with early metabolic chemistry exploiting NAD+ or nicotinamide mononucleotide and not simpler molecules.

LncRNA NEAT1 in the pathogenesis of liver-related diseases.

Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long noncoding RNA (lncRNA) that is widely expressed in a variety of mammalian cell types. Altered expression levels of the lncRNA NEAT1 have been reported in liver-related disorders including cancer, fatty liver disease, liver fibrosis, viral hepatitis, and hepatic ischemia. lncRNA NEAT1 mostly acts as a competing endogenous RNA (ceRNA) to sponge various miRNAs (miRs) to regulate different functions. In regard to hepatic cancers, the elevated expression of NEAT1 has been reported to have a relation with the proliferation, migration, angiogenesis, apoptosis, as well as epithelial-mesenchymal transition (EMT) of cancer cells. Furthermore, NEAT1 upregulation has contributed to the pathogenesis of other liver diseases such as fibrosis. In this review, we summarize and discuss the molecular mechanisms by which NEAT1 contributes to liver-related disorders including acute liver failure, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, and liver carcinoma, providing novel insights and introducing NEAT1 as a potential therapeutic target in these diseases.

Development and implementation of a strategy for early diagnosis and management of scrub typhus: an emerging public health threat.

Scrub typhus, caused by Orientia tsutsugamushi, is a re-emerging zoonotic disease in the tropics with considerable morbidity and mortality rates. This disease, which is mostly prevalent in rural areas, remains underdiagnosed and underreported because of the low index of suspicion and non-specific clinical presentation. Limited access to healthcare, diagnostics, and treatment in rural settings further makes it challenging to distinguish it from other febrile illnesses. While easily treatable, improper treatment leads to severe forms of the disease and even death. As there is no existing public health program to address scrub typhus in India, there is an urgent need to design a program and test its effectiveness for control and management of the disease. With this backdrop, this implementation research protocol has been developed for a trial in few of the endemic "pockets" of Odisha, an eastern Indian state that can be scalable to other endemic areas of the country, if found effective. The main goal of the proposed project is to include scrub typhus as a differential diagnosis of fever cases in every tier of the public health system, starting from the community level to the health system, for the early diagnosis among suspected cases and to ensure that individuals receive complete treatment. The current study aimed to describe the protocol of the proposed Scrub Typhus Control Program (STCP) in detail so that it can receive valuable views from peers which can further strengthen the attempt.

Altered TLR7 Expression-Mediated Immune Modulation Is Supportive of Persistent Replication and Intrauterine Transmission of HBV.

Hepatitis B Virus (HBV) is posing as a serious public health threat mainly due to its asymptomatic nature of infection in pregnancy and vertical transmission. Viral sensing toll-like receptors (TLR) and Interleukins (IL) are important molecules in providing an antiviral state. The study aimed to assess the role of TLR7-mediated immune modulation, which might have an impact in the intrauterine transmission of HBV leading to mother to child transmission of the virus. We investigated the expression pattern of TLR7, IL-3, and IL-6 by RT-PCR in the placentas of HBV-infected pregnant women to see their role in the intrauterine transmission of HBV. We further validated the expression of TLR7 in placentas using Immunohistochemistry. Expression analysis by RT-PCR of TLR7 revealed significant downregulation among the Cord blood (CB) HBV DNA positive and negative cases with mean ± standard deviation (SD) of 0.43 ± 0.22 (28) and 1.14 ± 0.57 (44) with p = 0.001. IL-3 and IL-6 expression revealed significant upregulation in the CB HBV DNA-positive cases with p = 0.001. Multinomial logistic regression analysis revealed that TLR7 and IL-3 fold change and mother HBeAg status are important predictors for HBV mother to child transmission. Immunohistochemistry revealed the decreased expression of TLR7 in CB HBV DNA-positive cases. This study reveals that the downregulation of TLR7 in the placenta along with CB HBV DNA-positive status may lead to intrauterine transmission of HBV, which may lead to vertical transmission of HBV.

Targeting notch-related lncRNAs in cancer: Insights into molecular regulation and therapeutic potential.

Cancer is a group of diseases marked by unchecked cell proliferation and the ability for the disease to metastasize to different body areas. Enhancements in treatment and early detection are crucial for improved outcomes. LncRNAs are RNA molecules that encode proteins and have a length of more than 200 nucleotides. LncRNAs are crucial for chromatin architecture, gene regulation, and other cellular activities that impact both normal growth & pathological processes, even though they are unable to code for proteins. LncRNAs have emerged as significant regulators in the study of cancer biology, with a focus on their intricate function in the Notch signaling pathway. The imbalance of this pathway is often linked to a variety of malignancies. Notch signaling is essential for cellular functions like proliferation, differentiation, and death. The cellular response is shaped by these lncRNAs through their modulation of essential Notch pathway constituents such as receptors, ligands, and downstream effectors around it. Furthermore, a variety of cancer types exhibit irregular expression of Notch-related lncRNAs, underscoring their potential use as therapeutic targets and diagnostic markers. Gaining an understanding of the molecular processes behind the interaction between the Notch pathway and lncRNAs will help you better understand the intricate regulatory networks that control the development of cancer. This can open up new possibilities for individualized treatment plans and focused therapeutic interventions. The intricate relationships between lncRNAs & the Notch pathway in cancer are examined in this review.

Dendritic cell-derived exosome (DEX) therapy for digestive system cancers: Recent advances and future prospect.

Tumor-mediated immunosuppression is a fundamental obstacle to the development of dendritic cell (DC)-based cancer vaccines, which despite their ability to stimulate host anti-tumor CD8 T cell immunity, have not been able to generate meaningful therapeutic responses. Exosomes are inactive membrane vesicles that are nanoscale in size and are produced by the endocytic pathway. They are essential for intercellular communication. Additionally, DC-derived exosomes (DEXs) contained MHC class I/II (MHCI/II), which is frequently complexed with antigens and co-stimulatory molecules and is therefore able to prime CD4 and CD8 T cells that are specific to particular antigens. Indeed, vaccines with DEXs have been shown to exhibit better anti-tumor efficacy in eradicating tumors compared to DC vaccines in pre-clinical models of digestive system tumors. Also, there is room for improvement in the tumor antigenic peptide (TAA) selection process. DCs release highly targeted exosomes when the right antigenic peptide is chosen, which could aid in the creation of DEX-based antitumor vaccines that elicit more targeted immune responses. Coupled with their resistance to tumor immunosuppression, DEXs-based cancer vaccines have been heralded as the superior alternative cell-free therapeutic vaccines over DC vaccines to treat digestive system tumors. In this review, current studies of DEXs cancer vaccines as well as potential future directions will be deliberated.

Role of Platelet-rich Plasma in Unexplained Recurrent Implantation Failure - A Systematic Review and Meta-analysis of Randomised Control Trials.

Background: Recurrent implantation failure (RIF) is a challenging clinical situation and various strategies have been tried to improve the pregnancy rate in RIF. Platelet-rich plasma (PRP), which is obtained from the autologous blood samples of a person and is multiple times richer in platelets and other growth factors helps improve endometrial receptivity. Objective: This study has been conducted to summarise the evidence and quality of evidence available so far regarding the role of PRP in cases of unexplained RIF. Materials and Methods: An electronic database search for randomised clinical trials comparing PRP against routine care in women with unexplained RIF was performed on PubMed, EMBASE, SCOPUS and Cochrane Central. Two independent reviewers conducted a literature search and retrieved data using the predefined eligibility criteria. Bias assessment was done using the Cochrane Collaboration Network Risk of Bias Tool version 2. The quality of evidence was determined and a summary of the findings table was prepared for individual outcomes using GRADEpro software. Results: We identified 1146 records, and after removing duplicates, 531 records were screened. Out of these, 22 studies reached full-text screening and nine studies were included in the final review. We are uncertain about the effect of PRP due to the very low quality of evidence and we have little confidence that the administration of PRP had any significant effect on improving the live birth rate in women with RIF (odds ratio [OR]: 7.32, 95% confidence interval [CI]: 4.54-11.81, I2 = 40%). Similarly, the quality of evidence was low for the clinical pregnancy rate, so we are uncertain if the administration of PRP had any significant effect on the clinical pregnancy rate (OR: 3.20, 95% CI: 2.38-4.28, I2 = 0%). Interpretation: The current review suggests that there may be some beneficial effects of PRP in women with RIF, but the quality of evidence is very low and we are uncertain of the benefit and have little confidence in these findings. Limitations: Limitations are the small sample size of most studies, a short follow-up period, non-uniformity in the definition of outcomes and very low quality of evidence. Registration: The protocol was registered on PROSPERO (CRD42021292209).

Subarachnoid Neurocysticercosis Case Series Reveals a Significant Delay in Diagnosis-Requiring a High Index of Suspicion Among Those at Risk.

Subarachnoid neurocysticercosis can be challenging to recognize, which often leads to a delay in diagnosis. We report 3 cases presenting as chronic headache disorders that highlight the unique manifestations seen with this form of neurocysticercosis and the role that the infectious diseases consultant can play in ensuring a timely diagnosis.

OMA1-Mediated Mitochondrial Dynamics Balance Organellar Homeostasis Upstream of Cellular Stress Responses.

In response to cellular metabolic and signaling cues, the mitochondrial network employs distinct sets of membrane-shaping factors to dynamically modulate organellar structures through a balance of fission and fusion. While these organellar dynamics mediate mitochondrial structure/function homeostasis, they also directly impact critical cell-wide signaling pathways such as apoptosis, autophagy, and the integrated stress response (ISR). Mitochondrial fission is driven by the recruitment of the cytosolic dynamin-related protein-1 (DRP1), while fusion is carried out by mitofusins 1 and 2 (in the outer membrane) and optic atrophy-1 (OPA1) in the inner membrane. This dynamic balance is highly sensitive to cellular stress; when the transmembrane potential across the inner membrane (Δψm) is lost, fusion-active OPA1 is cleaved by the overlapping activity with m-AAA protease-1 (OMA1 metalloprotease, disrupting mitochondrial fusion and leaving dynamin-related protein-1 (DRP1)-mediated fission unopposed, thus causing the collapse of the mitochondrial network to a fragmented state. OMA1 is a unique regulator of stress-sensitive homeostatic mitochondrial balance, acting as a key upstream sensor capable of priming the cell for apoptosis, autophagy, or ISR signaling cascades. Recent evidence indicates that higher-order macromolecular associations within the mitochondrial inner membrane allow these specialized domains to mediate crucial organellar functionalities.

Somatic Tumor Testing in Prostate Cancer: Experience of a Tertiary Care Center Including Pathologist-Driven Reflex Testing of Localized Tumors at Diagnosis.

Somatic tumor testing in prostate cancer (PCa) can guide treatment options by identifying clinically actionable variants in DNA damage repair genes, including acquired variants not detected using germline testing alone. Guidelines currently recommend performing somatic tumor testing in metastatic PCa, whereas there is no consensus on the role of testing in regional disease, and the optimal testing strategy is only evolving. This study evaluates the frequency, distribution, and pathologic correlates of somatic DNA damage repair mutations in metastatic and localized PCa following the implementation of pathologist-driven reflex testing at diagnosis. A cohort of 516 PCa samples were sequenced using a custom next-generation sequencing panel including homologous recombination repair and mismatch repair genes. Variants were classified based on the Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists guidelines. In total, 183 (35.5%) patients had at least one variant, which is as follows: 72 of 516 (13.9%) patients had at least 1 tier I or tier II variant, whereas 111 of 516 (21.5%) patients had a tier III variant. Tier I/II variant(s) were identified in 27% (12/44) of metastatic biopsy samples and 13% (61/472) of primary samples. Overall, 12% (62/516) of patients had at least 1 tier I/II variant in a homologous recombination repair gene, whereas 2.9% (10/516) had at least 1 tier I/II variant in a mismatch repair gene. The presence of a tier I/II variant was not significantly associated with the grade group (GG) or presence of intraductal/cribriform carcinoma in the primary tumor. Among the 309 reflex-tested hormone-naive primary tumors, tier I/II variants were identified in 10% (31/309) of cases, which is as follows: 9.2% (9/98) GG2; 9% (9/100) GG3; 9.1% (4/44) GG4; and 13.4% (9/67) GG5 cases. Our findings confirm the use of somatic tumor testing in detecting variants of clinical significance in PCa and provide insights that can inform the design of testing strategies. Pathologist-initiated reflex testing streamlines the availability of the results for clinical decision-making; however, pathologic parameters such as GG and the presence of intraductal/cribriform carcinoma may not be reliable to guide patient selection.

A Novel Non-Psychoactive Fatty Acid from a Marine Snail, Conus inscriptus, Signals Cannabinoid Receptor 1 (CB1) to Accumulate Apoptotic C16:0 and C18:0 Ceramides in Teratocarcinoma Cell Line PA1.

The cannabinoid-type I (CB1) receptor functions as a double-edged sword to decide cell fate: apoptosis/survival. Elevated CB1 receptor expression is shown to cause acute ceramide accumulation to meet the energy requirements of fast-growing cancers. However, the flip side of continual CB1 activation is the initiation of a second ceramide peak that leads to cell death. In this study, we used ovarian cancer cells, PA1, which expressed CB1, which increased threefold when treated with a natural compound, bis(palmitoleic acid) ester of a glycerol (C2). This novel compound is isolated from a marine snail, Conus inscriptus, using hexane and the structural details are available in the public domain PubChem database (ID: 14275348). The compound induced two acute ceramide pools to cause G0/G1 arrest and killed cells by apoptosis. The compound increased intracellular ceramides (C:16 to 7 times and C:18 to 10 times), both of which are apoptotic inducers in response to CB1 signaling and thus the compound is a potent CB1 agonist. The compound is not genotoxic because it did not induce micronuclei formation in non-cancerous Chinese hamster ovarian (CHO) cells. Since the compound induced the cannabinoid pathway, we tested if there was a psychotropic effect in zebrafish models, however, it was evident that there were no observable neurobehavioral changes in the treatment groups. With the available data, we propose that this marine compound is safe to be used in non-cancerous cells as well as zebrafish. Thus, this anticancer compound is non-toxic and triggers the CB1 pathway without causing psychotropic effects.

Contractile vacuoles: a rapidly expanding (and occasionally diminishing?) understanding.

Osmoregulation is the homeostatic mechanism essential for the survival of organisms in hypoosmotic and hyperosmotic conditions. In freshwater or soil dwelling protists this is frequently achieved through the action of an osmoregulatory organelle, the contractile vacuole. This endomembrane organelle responds to the osmotic challenges and compensates by collecting and expelling the excess water to maintain the cellular osmolarity. As compared with other endomembrane organelles, this organelle is underappreciated and under-studied. Here we review the reported presence or absence of contractile vacuoles across eukaryotic diversity, as well as the observed variability in the structure, function, and molecular machinery of this organelle. Our findings highlight the challenges and opportunities for constructing cellular and evolutionary models for this intriguing organelle.