Larval and adult morphology of Photuriselliptica Olivier (Coleoptera, Lampyridae) and a Halloweeny case of cave-dwelling firefly larva feeding on bat guano.

The predatory firefly Photuriselliptica is common throughout the Atlantic Forest and has been proposed as a biomonitor due to the species' narrow niche and elevational range. However, the species is only known from adults, and a more effective monitoring of its populations hinges on the lack of knowledge on their immature stages. Recent sampling in ferruginous caves and inserted in other lithologies, on sites in the Atlantic Forest and Cerrado, have led to the capture of firefly larvae later reared to adults in the lab. Firefly larvae have been reported in South American caves before; however, they have only been identified to family due to the adult-biased taxonomy of Lampyridae. Here, we provide an updated diagnosis of Photuriselliptica, describe its immature stages for the first time, and update the distribution of the species. The larvae of Photuriselliptica were observed to interact with guano of several bat species, including that of vampire bats. These observations are consistent with the less specialized feeding preferences of photurine larvae, unlike most other firefly taxa, which specialize in gastropods and earthworms. It is yet unclear whether P.elliptica are cave specialists. However, since its occurrence outside caves remains unknown, protecting cave environments must be considered in conservation strategies for this important biomonitor species.

Glowing wonders: exploring the diversity and ecological significance of bioluminescent organisms in Brazil.

Bioluminescence, the emission of light by living organisms, is a captivating and widespread phenomenon with diverse ecological functions. This comprehensive review explores the biodiversity, mechanisms, ecological roles, and conservation challenges of bioluminescent organisms in Brazil, a country known for its vast and diverse ecosystems. From the enchanting glow of fireflies and glow-in-the-dark mushrooms to the mesmerizing displays of marine dinoflagellates and cnidarians, Brazil showcases a remarkable array of bioluminescent species. Understanding the biochemical mechanisms and enzymes involved in bioluminescence enhances our knowledge of their evolutionary adaptations and ecological functions. However, habitat loss, climate change, and photopollution pose significant threats to these bioluminescent organisms. Conservation measures, interdisciplinary collaborations, and responsible lighting practices are crucial for their survival. Future research should focus on identifying endemic species, studying environmental factors influencing bioluminescence, and developing effective conservation strategies. Through interdisciplinary collaborations, advanced technologies, and increased funding, Brazil can unravel the mysteries of its bioluminescent biodiversity, drive scientific advancements, and ensure the long-term preservation of these captivating organisms.

Prioritization of genes for translation: a computational approach.

INTRODUCTION: Gene identification for genetic diseases is critical for the development of new diagnostic approaches and personalized treatment options. Prioritization of gene translation is an important consideration in the molecular biology field, allowing researchers to focus on the most promising candidates for further investigation. AREAS COVERED: In this paper, we discussed different approaches to prioritize genes for translation, including the use of computational tools and machine learning algorithms, as well as experimental techniques such as knockdown and overexpression studies. We also explored the potential biases and limitations of these approaches and proposed strategies to improve the accuracy and reliability of gene prioritization methods. Although numerous computational methods have been developed for this purpose, there is a need for computational methods that incorporate tissue-specific information to enable more accurate prioritization of candidate genes. Such methods should provide tissue-specific predictions, insights into underlying disease mechanisms, and more accurate prioritization of genes. EXPERT OPINION: Using advanced computational tools and machine learning algorithms to prioritize genes, we can identify potential targets for therapeutic intervention of complex diseases. This represents an up-and-coming method for drug development and personalized medicine.

Evaluation of Mitochondrial Phagy (Mitophagy) in Human Non-small Adenocarcinoma Tumor Cells.

Non-small cell lung cancer (NSCLC) is a predominant form of lung cancer characterized by its aggressive nature and high mortality rate, primarily due to late-stage diagnosis and metastatic spread. Recent studies underscore the pivotal role of mitophagy, a selective form of autophagy targeting damaged or superfluous mitochondria, in cancer biology, including NSCLC. Mitophagy regulation may influence cancer cell survival, proliferation, and metastasis by modulating mitochondrial quality and cellular energy homeostasis. Herein, we present a comprehensive methodology developed in our laboratory for the evaluation of mitophagy in NSCLC tumor cells. Utilizing a combination of immunoblotting, immunocytochemistry, and fluorescent microscopy, we detail the steps to quantify early and late mitophagy markers and mitochondrial dynamics. Our findings highlight the potential of targeting mitophagy pathways as a novel therapeutic strategy in NSCLC, offering insights into the complex interplay between mitochondrial dysfunction and tumor progression. This study not only sheds light on the significance of mitophagy in NSCLC but also establishes a foundational approach for its investigation, paving way for future research in this critical area of cancer biology.

A Lipidomics Approach to Determine the Role of Lipids and Its Crosstalk with Autophagy in Lung Cancer Metastasis.

Non-small cell lung cancer (NSCLC) is among the most malignant tumors with high propensity for metastasis and is the leading cause of cancer-related death globally. Most patients present with regional and distant metastasis, associated with poor prognosis. Lipids may play an essential role in either activating or inhibiting detachment-induced apoptosis (anoikis), where the latter is a crucial mechanism to prevent metastasis, and it may have a cross-talk with autophagy. Autophagy has been shown to be induced in various human cancer metastasis, modulating tumor cell motility and invasion, cancer cell differentiation, resistance to anoikis, and epithelial to mesenchymal transition. Hence, it may play a crucial role in the transition of benign to malignant phenotypes, the core of metastasis initiation. Here, we provide a method we have established in our laboratory for detecting lipids in attached and detached non-small lung cancer cells and show how to analyze lipidomics data to find its correlation with autophagy-related pathways.

Transforming Growth Factor Beta and Alveolar Rhabdomyosarcoma: A Challenge of Tumor Differentiation and Chemotherapy Response.

Alveolar rhabdomyosarcoma (ARMS), an invasive subtype of rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes, PAX3-FOXO1 or PAX7-FOXO1. ARMS patients exhibit an overexpression of the pleiotropic cytokine transforming growth factor beta (TGF-ß). This overexpression of TGF-ß1 causes an increased expression of a downstream transcription factor called SNAIL, which promotes epithelial to mesenchymal transition (EMT). Overexpression of TGF-ß also inhibits myogenic differentiation, making ARMS patients highly resistant to chemotherapy. In this review, we first describe different types of RMS and then focus on ARMS and the impact of TGF-ß in this tumor type. We next highlight current chemotherapy strategies, including a combination of the FDA-approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC); cabozantinib; bortezomib; vinorelbine; AZD 1775; and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS, which include all-trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-ß1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.

The role of BCL2L13 in glioblastoma: turning a need into a target.

Glioblastoma (GBM) is the most common aggressive central nervous system cancer. GBM has a high mortality rate, with a median survival time of 12-15 months after diagnosis. A poor prognosis and a shorter life expectancy may result from resistance to standard treatments such as radiation and chemotherapy. Temozolomide has been the mainstay treatment for GBM, but unfortunately, there are high rates of resistance with GBM bypassing apoptosis. A proposed mechanism for bypassing apoptosis is decreased ceramide levels, and previous research has shown that within GBM cells, B cell lymphoma 2-like 13 (BCL2L13) can inhibit ceramide synthase. This review aims to discuss the causes of resistance in GBM cells, followed by a brief description of BCL2L13 and an explanation of its mechanism of action. Further, lipids, specifically ceramide, will be discussed concerning cancer and GBM cells, focusing on ceramide synthase and its role in developing GBM. By gathering all current information on BCL2L13 and ceramide synthase, this review seeks to enable an understanding of these pieces of GBM in the hope of finding an effective treatment for this disease.

Efficacy of either orally administered fluralaner or topically administered imidacloprid/flumethrin for controlling Rhipicephalus sanguineus sensu lato premises infestations.

BACKGROUND: Adult, nymph, and larval Rhipicephalus sanguineus sensu lato infest dogs and thrive in premises including homes and kennels. Ticks emerge from hiding to seek and attach to dogs, engorge, then leave their hosts to hide then molt or oviposit. This study evaluated the effect of either external or systemic canine treatment on R. sanguineus s.l. populations in premises. METHODS: Thirty-two dogs in eight kennels were divided into three groups; one group (eight dogs in two kennels) served as untreated controls; one group (12 dogs in three kennels) received oral fluralaner (25-56 mg/kg); and one group (12 dogs in three kennels) received topical flumethrin/imidacloprid impregnated collars. Treatments were administered once on day 0. Prior to treatment, R. sanguineus s.l. infestations were established in kennels holding dogs, by placing ticks every 2 weeks from day -84 through day -14. Kennel surfaces (walls and floors) were smooth except for uniform "hideouts" to permit precise off-host tick counting. RESULTS: Control dog kennel mean tick counts (all life stages) increased from 737 ticks/kennel at day -7 to 2213 at day 63 when all control kennel dogs were acaricide-treated as a humane endpoint. Kennels housing dogs subsequently treated with systemic fluralaner had a mean of 637 counted ticks/kennel on study day -7 (7 days before treatment). One fluralaner treatment eliminated all premises ticks (100% reduction) by day 70, and these kennels remained tick-free through study completion (day 84). Kennels housing dogs subsequently treated with an external imidacloprid/flumethrin collar had a mean of 614 counted ticks/kennel at study day -7. Collar treatment reduced counts by 90% on day 63, with kennel tick counts climbing after this and ending the study with a 75% reduction. Systemic fluralaner treatment was significantly (P = 0.003) more effective at reducing engorged adult female tick counts than external imidacloprid/flumethrin treatment. CONCLUSIONS: Fluralaner treatment eliminated off-host R. sanguineus life stages in infested kennels by day 70 following treatment and was significantly more effective than imidacloprid/flumethrin collar treatment in reducing the premises population of engorged female ticks. Imidacloprid/flumethrin treatment did not eliminate premises tick populations, with populations increasing before the study end.

Epidemiological Profile of Victim Patients of Facial Canine and Human Bites in a Public Hospital.

INTRODUCTION: Bites are among the most common types of trauma to which humans are exposed. The possibility of disfiguring lesions and the transmission of infectious diseases with high morbidity make this trauma a public health problem. METHOD: This was a retrospective, descriptive study that analyzed the medical records of patients treated at the Emergency Unit of the Plastic Surgery Service of the Asa Norte Regional Hospital from March 2019 to March 2020. The variables analyzed included age, sex, origin, time interval from aggression to hospital care, aggressor agent, wound site, lesion characteristics, and treatment. RESULTS: A total of 103 patients with a mean age of 25 years were evaluated. Most patients were male (57.3%), and 73.8% were from the Federal District. The most common type of treatment was direct suturing in 77.7% of cases, followed by local flaps (15.5%) or grafts (4.9%). There were no deaths or infections reported. CONCLUSION: The predominant profile of a facial bite victim is a young male adult living in the Federal District, bitten by a canine and treated with direct sutures. Adequate treatment for animal bites should include prevention of infection, such as rabies and tetanus, as well as primary wound closure for achieving a better prognosis and satisfactory esthetics for the patient.

Description of immature stages and redescription of adults of Monocrepidius fuscofasciatus (Eschscholtz, 1829) (Elateridae, Agrypninae, Oophorini).

Monocrepidius Eschscholtz, 1829, previously Conoderus Eschscholtz, 1829, is one of the largest genera in Elateridae, with about 380 species distributed worldwide, with the majority of diversity in Australian and Neotropical regions. Several species groups have been recognized in Monocrepidius. Monocrepidius fuscofasciatus (Eschscholtz 1829) belongs to Candèze's section I with seven species distributed in South America, predominantly in Brazil. Larvae of M. fuscofasciatus is undescribed and distribution of this species is poorly known. In the present work we describe mature larva, pupa and redescribe adults of M. fuscofasciatus, and also add information about distribution of this species. Monocrepidius fuscofasciatus larva is similar to that of M. malleatus Germar, 1824, its closest species with known larva. They differ from other American species in the presence of penicillus on mandible and abdominal tergum IX more setose, with a lateral row of 6 or 7 setae. In the other species, the penicillus is absent and the lateral row bears 2 or 3 setae. These results corroborate that larval evidence is useful in the taxonomy of this genus.

Ceramides and ceramide synthases in cancer: Focus on apoptosis and autophagy.

Different studies corroborate a role for ceramide synthases and their downstream products, ceramides, in modulation of apoptosis and autophagy in the context of cancer. These mechanisms of regulation, however, appear to be context dependent in terms of ceramides' fatty acid chain length, subcellular localization, and the presence or absence of their downstream targets. Our current understanding of the role of ceramide synthases and ceramides in regulation of apoptosis and autophagy could be harnessed to pioneer the development of new treatments to activate or inhibit a single type of ceramide synthase, thereby regulating the apoptosis induction or cross talk of apoptosis and autophagy in cancer cells. Moreover, the apoptotic function of ceramide suggests that ceramide analogues can pave the way for the development of novel cancer treatments. Therefore, in the current review paper we discuss the impact of ceramide synthases and ceramides in regulation of apoptosis and autophagy in context of different types of cancers. We also briefly introduce the latest information on ceramide synthase inhibitors, their application in diseases including cancer therapy, and discuss approaches for drug discovery in the field of ceramide synthase inhibitors. We finally discussed strategies for developing strategies to use lipids and ceramides analysis in biological fluids for developing early biomarkers for cancer.

Integrating Multi-Omics Analysis for Enhanced Diagnosis and Treatment of Glioblastoma: A Comprehensive Data-Driven Approach.

The most aggressive primary malignant brain tumor in adults is glioblastoma (GBM), which has poor overall survival (OS). There is a high relapse rate among patients with GBM despite maximally safe surgery, radiation therapy, temozolomide (TMZ), and aggressive treatment. Hence, there is an urgent and unmet clinical need for new approaches to managing GBM. The current study identified modules (MYC, EGFR, PIK3CA, SUZ12, and SPRK2) involved in GBM disease through the NeDRex plugin. Furthermore, hub genes were identified in a comprehensive interaction network containing 7560 proteins related to GBM disease and 3860 proteins associated with signaling pathways involved in GBM. By integrating the results of the analyses mentioned above and again performing centrality analysis, eleven key genes involved in GBM disease were identified. ProteomicsDB and Gliovis databases were used for determining the gene expression in normal and tumor brain tissue. The NetworkAnalyst and the mGWAS-Explorer tools identified miRNAs, SNPs, and metabolites associated with these 11 genes. Moreover, a literature review of recent studies revealed other lists of metabolites related to GBM disease. The enrichment analysis of identified genes, miRNAs, and metabolites associated with GBM disease was performed using ExpressAnalyst, miEAA, and MetaboAnalyst tools. Further investigation of metabolite roles in GBM was performed using pathway, joint pathway, and network analyses. The results of this study allowed us to identify 11 genes (UBC, HDAC1, CTNNB1, TRIM28, CSNK2A1, RBBP4, TP53, APP, DAB1, PINK1, and RELN), five miRNAs (hsa-mir-221-3p, hsa-mir-30a-5p, hsa-mir-15a-5p, hsa-mir-130a-3p, and hsa-let-7b-5p), six metabolites (HDL, N6-acetyl-L-lysine, cholesterol, formate, N, N-dimethylglycine/xylose, and X2. piperidinone) and 15 distinct signaling pathways that play an indispensable role in GBM disease development. The identified top genes, miRNAs, and metabolite signatures can be targeted to establish early diagnostic methods and plan personalized GBM treatment strategies.

New Visions on Natural Products and Cancer Therapy: Autophagy and Related Regulatory Pathways.

Macroautophagy (autophagy) has been a highly conserved process throughout evolution and allows cells to degrade aggregated/misfolded proteins, dysfunctional or superfluous organelles and damaged macromolecules, in order to recycle them for biosynthetic and/or energetic purposes to preserve cellular homeostasis and health. Changes in autophagy are indeed correlated with several pathological disorders such as neurodegenerative and cardiovascular diseases, infections, cancer and inflammatory diseases. Conversely, autophagy controls both apoptosis and the unfolded protein response (UPR) in the cells. Therefore, any changes in the autophagy pathway will affect both the UPR and apoptosis. Recent evidence has shown that several natural products can modulate (induce or inhibit) the autophagy pathway. Natural products may target different regulatory components of the autophagy pathway, including specific kinases or phosphatases. In this review, we evaluated ~100 natural compounds and plant species and their impact on different types of cancers via the autophagy pathway. We also discuss the impact of these compounds on the UPR and apoptosis via the autophagy pathway. A multitude of preclinical findings have shown the function of botanicals in regulating cell autophagy and its potential impact on cancer therapy; however, the number of related clinical trials to date remains low. In this regard, further pre-clinical and clinical studies are warranted to better clarify the utility of natural compounds and their modulatory effects on autophagy, as fine-tuning of autophagy could be translated into therapeutic applications for several cancers.

Potential role of TGFΒ and autophagy in early crebellum development.

During development, the interconnected generation of various neural cell types within the cerebellar primordium is essential. Over embryonic (E) days E9-E13, Purkinje cells (PCs), and cerebellar nuclei (CN) neurons are among the created primordial neurons. The molecular and cellular mechanisms fundamental for the early cerebellar neurogenesis, migration/differentiation, and connectivity are not clear yet. Autophagy has a vital role in controlling cellular phenotypes, such as epithelial-to-mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT). Transforming growth factor-beta 1 (TGF-ß1) is the main player in pre-and postnatal development and controlling cellular morphological type via various mechanisms, such as autophagy. Thus, we hypothesized that TGF-ß1 may regulate early cerebellar development by modifying the levels of cell adhesion molecules (CAMs) and consequently autophagy pathway in the mouse cerebellar primordium. We demonstrated the stimulation of the canonical TGF-ß1 signaling pathway at the point that concurs with the generation of the nuclear transitory zone and PC plate in mice. Furthermore, our data show that the stimulated TGF-ß1 signaling pathway progressively and chronologically could upregulate the expression of ß-catenin (CTNNB1) and N-cadherin (CDH2) with the most expression at E11 and E12, leading to upregulation of chromodomain helicase DNA binding protein 8 (CDH8) and neural cell adhesion molecule 1 (NCAM1) expression, at E12 and E13. Finally, we demonstrated that the stimulated TGF-ß signaling pathway may impede the autophagic flux at E11/E12. Nevertheless, basal autophagy flux happens at earlier developmental phases from E9-E10. Our study determined potential role of the TGF-ß signaling and its regulatory impacts on autophagic flux during cerebellar development and cadherin expression, which can facilitate the proliferation, migration/differentiation, and placement of PCs and the CN neurons in their designated areas.

Lithium treatment in children and adolescents with anorexia nervosa: clinical use, side effects and tolerability.

PURPOSE: Current guidelines, due to potential toxicity and lack of clinical evidence, do not recommend the use of lithium in the treatment of Anorexia Nervosa (AN). Scarce evidence is available on the use, side effects, and tolerability of this drug in children and adolescents with AN, a population characterized by specific clinical, metabolic, and hydro-electrolytic balance features. Here we report a case series of children and adolescents hospitalized for AN and treated with lithium. METHODS: Case series reporting the use of lithium in 7 female young patients with AN. Reasons for introduction, dosages, formulation, plas-ma levels, adverse drug reactions (ADR) and modifi-cations of electrocardiogram (EKG) and plasma levels of glucose, cholesterol, creatinine, urea, sodium, and thyroid-stimulating hormone (TSH) were assessed. Re-sults. Reasons for the introduction of lithium included unstable mood, insufficient compliance with nutri-tional programs, and psychomotor agitation. In all of the patients an improvement on target symptoms was observed. Lithium was started at 171.4 (+/-56.7) mg/day, up to 600.0 (+/-173.2) mg/day. The most frequent scheme was three times daily. The mean plasmatic concentration was 0.6 (+/-0.3) mmol/L at one month. One pa-tient experienced polyuria, polydipsia and dry mouth, and another showed increased creatinine kinase. No major modifications of EKG, glucose, cholesterol, cre-atinine, urea, sodium emerged. CONCLUSIONS: In this sample of children and adolescents hospitalized for AN, lithium was administered to improve psychiatric symptoms impairing compliance. All the patients experienced an improvement on these symptoms after being admin-istered lithium. ADR were reported in 2 cases. These data should be investigated in wider populations and controlled studies.

A comprehensive review and call for studies on firefly larvae.

BACKGROUND: Fireflies (Coleoptera: Lampyridae) are commonly recognized by adult traits, such as a soft exoskeleton, lanterns and associated glow and flash patterns, but their larval stage is far less appreciated. However, fireflies spend most of their lives as larvae, and adults of most species rely solely on resources previously obtained. Therefore, studying the immature stages is imperative towards a comprehensive understanding of fireflies. This paper reviews and indicates key gaps in the biology of firefly larvae based on available literature. METHODOLOGY: We reviewed the literature on firefly larvae to identify key issues and important taxonomic, geographic, and subject biases and gaps. RESULTS: We found 376 papers that included information on firefly larvae. Only 139 species in 47 genera across eight of eleven lampyrid subfamilies have been studied during larval stages. These numbers reveal a staggering gap, since 94% of species and over half of the genera of fireflies were never studied in a crucial stage of their life cycle. Most studies on firefly larvae focus on two subfamilies (Luciolinae and Lampyrinae) in four zoogeographic regions (Sino-Japanese, Oriental, Nearctic, and Palearctic), whereas the other subfamilies and regions remain largely unstudied. These studies mainly dealt with morphology and behavior, other subjects remaining greatly understudied by comparison, including habitats, life cycle, physiology and interactions. CONCLUSIONS: Together, these literature biases and gaps highlight how little is known about firefly larvae, and warmly invite basic and applied research, in the field and in the lab, to overcome these limitations and improve our understanding of firefly biology to better preserve them.

Association among Autistic Traits, Treatment Intensity and Outcomes in Adolescents with Anorexia Nervosa: Preliminary Results.

The present study investigates the impact of Autism Spectrum Disorder (ASD) traits on the treatment intensity and outcomes (psychopathology and weight) of 22 adolescent inpatients with Anorexia Nervosa (AN), who were selected on the basis of suspected ASD traits. ASD traits were measured at admission (T0) using the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and the Autism-Spectrum Quotient (AQ). Psychopathology was measured with Eating Disorder Inventory-3 (EDI-3) and Self-Administered Psychiatric Scales for Children and Adolescents (SAFA) at admission and discharge (T0, T1). Percentage BMI was assessed at admission, discharge, first follow-up (T2, 7-22 days) and second follow-up (T3, 22-45 days). Results were controlled for age and EDI-3 global psychological maladjustment. When compared with other patients with AN, AN individuals with ADOS-2 and AQ diagnostic scores for ASD showed overlapping types of treatments, as well as psychopathological and weight outcomes. ASD total scores were not correlated with treatment intensity or treatment outcomes. Preliminary results show that ASD traits do not impact treatment intensity and outcomes in adolescents with AN and suspected ASD traits.

Hide-and-Seek with Tiny Neotenic Beetles in One of the Hottest Biodiversity Hotspots: Towards an Understanding of the Real Diversity of Jurasaidae (Coleoptera: Elateroidea) in the Brazilian Atlantic Forest.

Jurasaidae are a family of neotenic elateroid beetles which was described recently from the Brazilian Atlantic Forest biodiversity hotspot based on three species in two genera. All life stages live in the soil, including the larviform females, and only adult males are able to fly. Here, we report the discovery of two new species, Jurasai miraculum sp. nov. and J. vanini sp. nov., and a new, morphologically remarkable population of J. digitusdei Rosa et al., 2020. Our discovery sheds further light on the diversity and biogeography of the group. Most species of Jurasaidae are known from the rainforest remnants of the Atlantic Forest, but here for the first time we report a jurasaid species from the relatively drier Atlantic Forest/Caatinga transitional zone. Considering our recent findings, minute body size and cryptic lifestyle of all jurasaids, together with potentially high numbers of yet undescribed species of this family from the Atlantic Forest and possibly also other surrounding ecoregions, we call for both field research in potentially suitable localities as well as for a detailed investigation of a massive amount of already collected but still unprocessed materials deposited in a number of Brazilian institutes, laboratories and collections.

Adiponectin Synthesis, Secretion and Extravasation from Circulation to Interstitial Space.

Adiponectin, an adipokine that circulates as multiple multimeric complexes at high levels in serum, has antidiabetic, anti-inflammatory, antiatherogenic, and cardioprotective properties. Understanding the mechanisms regulating adiponectin's physiological effects is likely to provide critical insight into the development of adiponectin-based therapeutics to treat various metabolic-related diseases. In this review, we summarize our current understanding on adiponectin action in its various target tissues and in cellular models. We also focus on recent advances in two particular regulatory aspects; namely, the regulation of adiponectin gene expression, multimerization, and secretion, as well as extravasation of circulating adiponectin to the interstitial space and its degradation. Finally, we discuss some potential therapeutic approaches using adiponectin as a target and the current challenges facing adiponectin-based therapeutic interventions.