The antiapoptotic protein Bcl-2, overexpressed in many tumor cells, is an attractive target for potential small molecule anticancer drug discovery. Herein, we report a different structural modification approach on ABT-263 by merging the piperazinyl-phenyl fragment into a bicyclic framework leading to a series of novel analogues, among which tetrahydroisoquinoline 13 was nearly equally potent against Bcl-2 as ABT-263. Further SAR in the P4-interaction pocket affored the difluoroazetidine substituted analogue 55, which retained good Bcl-2 activity with improved Bcl-2/Bcl-xL selectivity.
This study examines the interaction between hERG and Kv4.3. The functional interaction between hERG and Kv4.3, expressed in a heterologous cell line, was studied using patch clamp techniques, western blot, immunofluorescence, and co-immunoprecipitation. Co-expression of Kv4.3 with hERG increased hERG current density (tail current after a step to +10 mV: 26 ± 3 versus 56 ± 7 pA/pF, p < 0.01). Kv4.3 co-expression also increased the protein expression and promoted the membrane localization of hERG. Western blot showed Kv4.3 increased hERG expression by Hsp70. hERG and Kv4.3 co-localized and co-immunoprecipitated in cultured 293 T cells, indicating physical interactions between hERG and Kv4.3 proteins in vitro. In addition, Hsp70 interacted with hERG and Kv4.3 respectively, and formed complexes with hERG and Kv4.3. The α subunit of Ito Kv4.3 can interact with and modify the localization of the α subunit of IKr hERG, thus providing potentially novel insights into the molecular mechanism of the malignant ventricular arrhythmia in heart failure.
Osteoporosis presents a challenge to the long-term success of osseointegration of endosseous implants. The bio-inspired 3,4-dihydroxy-L-phenylalanine (Dopa) coating is widely used as a basic layer to bind osteogenetic molecules that may improve osseointegration. To date, little attention has focused on application of Dopa alone or binding inhibitors of bone resorption in osteoporosis. Local use of a bisphosphonate such as zoledronic acid (ZA), an inhibitor of osteoclast-mediated bone resorption, has been proven to improve implant osseointegration. In this study, ovariectomized rats were divided into four groups and implanted with implants with different surface modifications: sandblasted and acid-etched (SLA), SLA modified with Dopa (SLA-Dopa), SLA modified with ZA (SLA-ZA), and SLA modified with Dopa and ZA (SLA-Dopa + ZA). Measurement of removal torque, micro-computed tomography and histology revealed a greater extent of bone formation around the three surface-modified implants than SLA-controls. No synergistic effect was observed for combined Dopa + ZA coating. Microarray analysis showed the Dopa coating inhibited expression of genes associated with osteoclast differentiation, similarly to the mechanism of action of ZA. Simple Dopa modification resulted in a similar improvement in osseointegration compared to ZA. Thus, our data suggest simple Dopa coating is promising strategy to promote osseointegration of implants in patients with osteoporosis.
One specific behavior can be synergistically modulated by different neural pathways. Medial septal (MS) cholinergic system innervates widespread cortical and subcortical regions and participates in pain modulation, but the underlying neural pathways are not fully understood. This study examined the contribution of MS cholinergic neurons and 2 neural pathways: MS-rostral anterior cingulate cortex (rACC) and MS-ventral hippocampal CA1 (vCA1), in modulating perceptual and affective pain behaviors in a mouse model of chronic inflammatory pain. We found that chronic pain activated MS cholinergic neurons and pyramidal neurons in the rACC, but suppressed pyramidal neuronal activities in the vCA1, all of which contributed to the maintenance of pathological pain. Chemogenetic inhibition of MS cholinergic neurons or the MS-rACC pathway inhibited rACC pyramidal neuronal activities and attenuated perceptual and affective dimensions of chronic pain. By contrast, chemogenetic activation of MS cholinergic neurons also produced analgesia, but by rescuing hypofunctional pyramidal neurons in vCA1. These results clearly demonstrate that the MS cholinergic system differentially modulates chronic inflammatory pain through MS-rACC or MS-vCA1 pathways. More significantly, our research provides evidence for a novel paradigm of neural circuit modulation: MS cholinergic inhibition and activation induce similar analgesia but through distinct neural pathways.
Aroma-active compounds and non-volatile substances determine the characteristic aroma and taste of yeast extract (YE). Changes in the characteristic aroma and taste of YE due to thermal reaction are rarely studied, and the relationship between aroma-active compounds and non-volatile compounds is not yet clear.
Non-volatile compounds identified by HPLC and LC/MS/MS were reduced by a rise in temperature, except for some amino acids. Peptides underwent degradation. In addition, a further rise in temperature above 120 °C resulted in a bitter and sour taste. Furans, pyrazines, thiophenes, thiazoles and some branched chain sulfur compounds were derived from GC/O/MS (SPME and SAFE). Sensory results revealed that the concentration of volatile compounds increased with an increase in temperature. The overall aroma profiles of YE at 25, 100 and 110 °C were buttery, green, nutty and meaty, while YE at 140 °C had a strong sour and sulfur odour.
The non-volatile compounds of YE were reduced and different volatile compounds were produced under different thermal treatments. There was a negative correlation between these two types of compounds. The different taste sensors and all precursors were correlated with each other. There are significant relationships between different odorants and aroma-active compounds of YE after thermal treatment. © 2018 Society of Chemical Industry.
Prostate cancer-associated non-coding RNA transcript-1(PCAT-1), which is a newly discovered long non-coding RNA, is up-regulated in various cancers. We conducted a meta-analysis to assess the clinicopathological and prognostic value of PCAT-1 in patients with malignant tumors.
A systematic literature search involved PubMed, Medline, Cochrane Library, Web of Science, EMBASE database, Ovid, Chinese CNKI, and the Chinese WanFang database. The role of PCAT-1 in cancers was evaluated by pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs).
A total of 1005 patients from nine studies were included in this meta-analysis. High expression of PCAT-1 was associated with depth of infiltration, lymph node metastasis, distant metastasis and TNM stage. However, increased PCAT-1 expression was not related to gender, tumor size and differentiation. Moreover, high PCAT-1 expression was associated with poor overall survival (OS) and disease-free survival (DFS), and the pooled results suggested that PCAT-1 expression can be an independent predictive factor for overall survival.
This meta-analysis provides evidence that PCAT-1 expression is closely correlated with depth of infiltration, lymph node metastasis, distant metastasis and TNM stage, and that increased PCAT-1 expression may be a potential prognostic biomarker in human cancers. However, more large-scale studies are warranted.
Strobilanthes A (1), a novel isocoumarin with an unusual tetrahydro-4H-pyran-4-one moiety fused isocoumarin core skeleton, together with a known compound (2) was isolated from Strobilanthes cusia. Its chemical structures were elucidated by 2D NMR spectroscopy, mass spectrometry and single-crystal X-ray diffraction analysis. The biosynthetic pathway of 1 could be supposed to be originally derived from 3-methylisocoumarin, a product of AA-MA pathway. Both of two compounds displayed anti-influenza virus activity in vitro.
Acrylamide (AA) is a high production volume chemical in industrial applications and widely found in baked or fried carbohydrate-rich foods. In this study, we unravelled that AA induced developmental toxicity associated with oxidative stress status and disordered lipid distribution in heart region of developing zebrafish. Treatment with AA caused a deficient cardiovascular system with significant heart malformation and dysfunction. We also found that AA could reduce the number of cardiomyocytes through the reduced capacity of cardiomyocyte proliferation rather than cell apoptosis. The cardiac looping and ballooning appeared abnormal though cardiac chamber-specific identity in the differentiated myocardium was maintained well after AA treatment through MF20/S46 immunofluorescence assay. Furthermore, treatment with AA disturbed the differentiation of atrioventricular canal, which was demonstrated by the disordered expressions of the atrioventricular boundary markers bmp4, tbx2b and notch1b and further confirmed by the ectopic expressions of the cardiac valve precursor markers has2, klf2a and nfatc1 through whole-mount in situ hybridization. Thus, our studies provide the evidence of cardiac developmental toxicity of AA in the cardiovascular system, and also raised health concern about the harm of trans-placental exposure to high level of AA for foetuses and the risk of high exposure to AA for the pregnant women.
Fabrication of antibacterial materials with sustained release of active components is of great importance for long-term antibacterial applications. Graphene oxide (GO) has been found to be an excellent carrier for accumulating the antibacterial peptide of G(IIKK)4I-NH2 and mediating its loading into the layer-by-layer (LBL) films for sustained release applications. G(IIKK)4I-NH2 takes random coiled conformation in monomeric state below 0.17 mM but self-assembles into supramolecular aggregates with α-helical secondary structure at higher concentrations. It can bind onto GO surface in both monomeric and aggregate states to form stable GO@G(IIKK)4I-NH2 composites. Upon binding, the local amphiphilic environment of GO surface induces a conformational transition of G(IIKK)4I-NH2 monomers from random coils to α-helix. The aggregate binding enhances the loading amount greatly. GO (1 mg) can load as high as 1.7 mg of peptide at saturation. This enables the GO@G(IIKK)4I-NH2 composites to serve as reservoirs for sustained release of active G(IIKK)4I-NH2 monomers. Moreover, G(IIKK)4I-NH2 itself shows low efficiency in LBL assembly, whereas the GO@G(IIKK)4I-NH2 composites are ideal LBL assembling units with highly enhanced loading efficiency of G(IIKK)4I-NH2. The LBL films involving degradable poly(β-amino esters) can realize sustained release of G(IIKK)4I-NH2 for bacteria killing in a well-controlled manner. This study demonstrates an efficient strategy for fabrication of long-durable antibacterial materials and surface coatings by using GO as the carrier for drug accumulation and loading.
Nonadiabatic excited-state molecular dynamics (NEXMD) has been used to study photodecomposition in a class of recently synthesized bicyclic conjugated energetic materials (CEMs) composed of fused tetrazole and tetrazine derivatives with increasing oxygen substitutions. Modification by oxygen functionalization has already been demonstrated to increase the two-photon absorption intensity in the target CEMs while simultaneously improving oxygen balance. Photodecomposition mechanisms in materials that undergo nonlinear absorption could be used to achieve controlled, direct optical initiation. Here, we use NEXMD simulations to model the nonradiative relaxation and photodecomposition in CEMs following photoexcitation by a simulated Nd:YAG laser pulse. Excess electronic energy is quickly converted into vibrational energy on a sub-100 fs time scale resulting in bond dissociation. We find that, for the studied tetrazine derivatives, the bicyclic framework is an important structural feature that enhances the photochemical quantum yield and the high atomic oxygen content increases the relaxation lifetime and opens additional photodissociation pathways targeting the oxygen-substituted sites. The presented analysis scheme based on bond orders in the swarm of NEXMD trajectories is a useful tool for determining photochemical reactions.
Rhizoctonia solani is a plant pathogenic fungus, which can infect a wide range of economic crops including rice. In this case, biological control of this pathogen is one of the fundmental way to effectively control this pathogen. The Pseudomonas parafulva strain PRS09-11288 was isolated from rice rhizosphere and shows biocontrol ability against R. solani. Here, we analyzed the P. parafulva genome, which is ~ 4.7 Mb, with 4310 coding sequences, 76 tRNAs, and 7 rRNAs. Genome analysis identified a phenazine biosynthetic pathway, which can produce antibiotic phenazine-1-carboxylic acid (PCA). This compound is responsible for biocontrol ability against R. solani Kühn, which is one of the most serious fungus disease on rice. Analysis of the phenazine biosynthesis gene mutant, ΔphzF, which is very important in this pathway, confirmed the relationship between the pathway and PCA production using LC-MS profiles. The annotated full genome sequence of this strain sheds light on the role of P. parafulva PRS09-11288 as a biocontrol bacterium.
Herein we reported Prussian blue nanoparticles (PBNPs) possess ascorbic acid oxidase (AAO)- and ascorbic acid peroxidase (APOD)-like activities, which suppressed the formation of harmful H2O2 and finally inhibited the anti-cancer efficiency of ascorbic acid (AA). This newly revealed correlation between iron and AA could provide new insight for the studies of nanozymes and free radical biology.
Hypoxia, and hypoxia inducible factor-1 (HIF-1), can induce tumor resistance to radiation therapy. To overcome hypoxia-induced radiation resistance, recent studies have described nanosystems to improve tumor oxygenation for immobilizing DNA damage and simultaneously initiate oxygen-dependent HIF-1α degradation. However, HIF-1α degradation is incomplete during tumor oxygenation treatment alone. Therefore, tumor oxygenation combined with residual HIF-1 functional inhibition is crucial to optimizing therapeutic outcomes of radiotherapy. Here, a reactive oxygen species (ROS) responsive nanoplatform is reported to successfully add up tumor oxygenation and HIF-1 functional inhibition. This ROS responsive nanoplatform, based on manganese dioxide (MnO2) nanoparticles, delivers the HIF-1 inhibitor acriflavine and other hydrophilic cationic drugs to tumor tissues. After reacting with overexpressed hydrogen peroxide (H2O2) within tumor tissues, Mn2+ and oxygen molecules are released for magnetic resonance imaging and tumor oxygenation, respectively. Cooperating with the HIF-1 functional inhibition, the expression of tumor invasion-related signaling molecules (VEGF, MMP-9) is obviously decreased to reduce the risk of metastasis. Furthermore, the nanoplatform could relieve T-cell exhaustion via downregulation of PD-L1, whose effects are similar to the checkpoint inhibitor PD-L1 antibody, and subsequently activates tumor-specific immune responses against abscopal tumors. These therapeutic benefits including increased X-ray-induced damage, downregulated resistance, and T-cell exhaustion related proteins expression achieved synergistically the optimal inhibition of tumor growth. Overall, this designed ROS responsive nanoplatform is of great potential in the sensitization of radiation for combating primary and metastatic tumors.
High fibular osteotomy has been preliminarily proved to be an effective treatment of knee osteoarthritis by excising a segment of bone at the proximal part of fibula. This imaginative procedure is clinical validated by its instant and explicit knee pain resorption and eventually deformity correction. The rationale of this treatment is named non-uniform settlement of the tibial plateau and used to elucidate the cause of knee joint degeneration, but cannot illuminate the reason of prompt postoperative pain resorption faithfully. To assist in better understanding of this therapeutic method and raising alert to possible unexpected complications, we proposed a new theory to elucidate the pain relief mechanism.
Adrenocortical cancer (ACC) is an orphan malignancy that results in heterogeneous clinical phenotypes and molecular genotypes. There are no curative treatments for this deadly cancer with 35% survival at five years. Our understanding of the underlying pathobiology and our ability to test novel therapeutic targets has been limited due to the lack of preclinical models. Here, we report the establishment of two new ACC cell lines and corresponding patient-derived xenograft (PDX) models. CU-ACC1 cell line and PDX were derived from a perinephric metastasis in a patient whose primary tumor secreted aldosterone. CU-ACC2 cell line and PDX were derived from a liver metastasis in a patient with Lynch syndrome. Short tandem repeat profiling confirmed consistent matches between human samples and models. Both exomic and RNA sequencing profiling were performed on the patient samples and the models, and hormonal secretion was evaluated in the new cell lines. RNA sequencing and immunohistochemistry confirmed the expression of adrenal cortex markers in the PDXs and human tumors. The new cell lines replicate two of the known genetic models of ACC. CU-ACC1 cells had a mutation in CTNNB1 and secreted cortisol but not aldosterone. CU-ACC2 cells had a TP53 mutation and loss of MSH2 consistent with the patient's known germline mutation causing Lynch syndrome. Both cell lines can be transfected and transduced with similar growth rates. These new preclinical models of ACC significantly advance the field by allowing investigation of underlying molecular mechanisms of ACC and the ability to test patient-specific therapeutic targets.
In 2011, DEHP (plasticizer) was reported to illegally be added in food and beverage products in Taiwan, which caused great concerns about food safety worldwide. DHEP has multiple toxic effects to human and animals such as endocrine disruption, cardiotoxicity, reproductive function, and development defects. However, the toxic effects of DEHP on mammalian oocyte quality are still unclear. Since MEHP is the active metabolite of DEHP in vivo, in this study we used porcine oocyte as model to explore the effects of MEHP on oocyte maturation and we also studied the effects of melatonin administration on MEHP exposure-induced meiosis defects. Our results showed that exposure to MEHP significantly decreased the polar body extrusion rate in porcine oocytes. Further study showed that cell cycle progression, meiotic spindle organization, and actin assembly were all disturbed after MEHP exposure. Moreover, the DNA and histone methylation levels were also affected, showing with altered 5mC and H3K4me2 levels. These results indicated that MEHP affected porcine oocyte maturation, while MEHP exposure-induced meiotic defects were all remarkably ameliorated by the administration of melatonin in porcine oocytes. We further tried to explore the causes of MEHP toxicity on oocytes, and we found that MEHP exposure resulted in significant elevations of oxidative stress and induced early apoptosis as well as elevated autophagy, while melatonin administration could reduce these. Taken together, our results indicated that MEHP exposure induced deterioration of oocyte quality, whereas melatonin supplement showed amelioration on oocyte maturation through its rescue effects on oocyte oxidative stress-mediated apoptosis and autophagy.
Photodynamic therapy (PDT) has attracted ever-growing attention as a promising modality for cancer treatment. However, due to poor tissue penetration by light, photodynamic therapy has rarely been used for deeply situated tumors. This problem can be solved if photosensitizers are activated by microwaves (MW) that are able to penetrate deeply into tissues. Here, for the first time, we report microwave-induced photodynamic therapy and exploit copper cysteamine nanoparticles as a new type of photosensitizer that can be activated by microwaves to produce singlet oxygen for cancer treatment. Both in vitro and in vivo studies on a rat osteosarcoma cell line (UMR 106-01) have shown significant cell destruction using copper cysteamine (Cu-Cy) under microwave activation. The heating effects and the release of copper ions from Cu-Cy upon MW stimulation are the main mechanisms for the generation of reactive oxygen species that are lethal bullets for cancer destruction. The copper cysteamine nanoparticle-based microwave-induced photodynamic therapy opens a new door for treating cancer and other diseases.
Lowering blood pressure (BP) after stroke remains a challenge, even in the context of clinical trials. The Secondary Prevention of Small Subcortical Strokes (SPS3) BP protocol, BP management during the study, and achieved BPs are described here.
Patients with recent symptomatic lacunar stroke were randomized to 1 of 2 levels of systolic BP (SBP) targets: lower: <130mm Hg, or higher: 130-149mm Hg. SBP management over the course of the trial was examined by race/ethnicity and other baseline conditions.
Mean SBP decreased for both groups from baseline to the last follow-up, from 142.4 to 126.7mm Hg for the lower SBP target group and from 143.6 to 137.4mm Hg for the higher SBP target group. At baseline, participants in both groups used an average of 1.7±1.2 antihypertensive medications, which increased to a mean of 2.4±1.4 (lower group) and 1.8±1.4 (higher group) by the end-study visit. It took an average of 6 months for patients to reach their SBP target, sustained to the last follow-up. Black participants had the highest proportion of SBP ≥150mm Hg at both study entry (40%) and end-study visit (17%), as compared with whites (9%) and Hispanics (11%).
These results show that it is possible to safely lower BP even to a SBP goal <130mm Hg in a variety of patients and settings, including private and academic centers in multiple countries. This provides further support for protocol-driven care in lowering BP and consequently reducing the burden of stroke.
The main complications of zirconia-based laminated systems are chipping and delamination of veneering porcelain, which has been found to be directly associated with the development of residual thermal stresses in the porcelain layer. This study investigates the effects of cooling rate and specimen geometry on the residual stress states in porcelain-veneered zirconia structures. Bilayers of three different shapes (bars, semi-cylindrical shells, and arch-cubic structures) with 1.5 mm and 0.7 mm thickness of dentin porcelain and zirconia framework, respectively, were subjected to two cooling protocols: slow cooling (SC) at 32 °C/min and extremely-slow cooling (XSC) at 2 °C/min. The residual thermal stresses were determined using the Vickers indentation method and validated by finite element analysis. The residual stress profiles were similar among geometries in the same cooling protocol. XSC groups presented significantly higher tensile stresses (p = 0.000), especially for curved interfaces. XSC is a time-consuming process that showed no beneficial effect regarding residual stresses compared to the manufacturer recommended slow cooling rate.
Surface-enhanced infrared absorption (SEIRA) spectroscopy has outstanding potential in chemical detection as a complement to surface-enhanced Raman spectroscopy (SERS), yet it has historically lagged well behind SERS in detection sensitivity. Here we report a new ultrasensitive infrared antenna designed to bring SEIRA spectroscopy into the few-molecule detection range. Our antenna consists of a bowtie-shaped Au structure with a sub-3 nm gap, positioned to create a cavity above a reflective substrate. This three-dimensional geometry tightly confines incident mid-infrared radiation into its ultrasmall junction, yielding a hot spot with a theoretical SEIRA enhancement factor of more than 107, which can be designed to span the range of frequencies useful for SEIRA. We quantitatively evaluated the IR detection limit of this antenna design using mixed monolayers of 4-nitrothiophenol (4-NTP) and 4-methoxythiolphenol (4-MTP). The optimized antenna structure allows the detection of as few as ∼500 molecules of 4-NTP and ∼600 molecules of 4-MTP with a standard commercial FTIR spectrometer. This strategy offers a new platform for analyzing the IR vibrations of minute quantities of molecules and lends insight into the ultimate limit of single-molecule SEIRA detection.
Metabolism has been shown to integrate with epigenetics and transcription to modulate cell fate and function. Beyond meeting the bioenergetic and biosynthetic demands of T-cell differentiation, whether metabolism might control T-cell fate by an epigenetic mechanism is unclear. Here, through the discovery and mechanistic characterization of a small molecule, (aminooxy)acetic acid, that reprograms the differentiation of T helper 17 (TH17) cells towards induced regulatory T (iTreg) cells, we show that increased transamination, mainly catalysed by GOT1, leads to increased levels of 2-hydroxyglutarate in differentiating TH17 cells. The accumulation of 2-hydroxyglutarate resulted in hypermethylation of the Foxp3 gene locus and inhibited Foxp3 transcription, which is essential for fate determination towards TH17 cells. Inhibition of the conversion of glutamate to α-ketoglutaric acid prevented the production of 2-hydroxyglutarate, reduced methylation of the Foxp3 gene locus, and increased Foxp3 expression. This consequently blocked the differentiation of TH17 cells by antagonizing the function of transcription factor RORγt and promoted polarization into iTreg cells. Selective inhibition of GOT1 with (aminooxy)acetic acid ameliorated experimental autoimmune encephalomyelitis in a therapeutic mouse model by regulating the balance between TH17 and iTreg cells. Targeting a glutamate-dependent metabolic pathway thus represents a new strategy for developing therapeutic agents against TH17-mediated autoimmune diseases.
An enantioselective sulfa-Michael-cyclization reaction was developed for the synthesis of 1,5-benzothiazepines with versatile pharmacological activities. The reaction between 2-aminothiophenol and α,β-unsaturated pyrazoleamides gave direct access to N-H-free 1,5-benzothiazepines in the presence of a chiral N,N'-dioxide/Yb(OTf)3 complex. Excellent enantioselectivities (up to 96 % ee) and high yields (up to 99 %) were obtained for a broad range of substrates under mild reaction conditions. This method provided a facile approach to the antidepressant drug (R)-(-)-Thiazesim.
This study aims to investigate the influence of ATP7B genetic polymorphism to platinum-based chemotherapy in Chinese Han lung cancer patients. A total of 338 Chinese Han lung cancer patients were enrolled in this study. All patients underwent at least two cycles of platinum-based chemotherapy. Four tag SNPs of ATP7B (rs1061472, rs9535826, rs7999812, and rs9535828) were selected to evaluate their impacts to platinum-based chemotherapy in these patients. ATP7B rs9535828 and rs9535826 were found to be associated with platinum resistance in Chinese Han lung cancer patients. Patients with A allele in ATP7B rs9535828 presented an increased susceptibility to platinum drugs (OR 1.96, 95 % CI 1.17-3.30, p < 0.01). Patients with G allele in ATP7B rs9535826 had the highest susceptibility to platinum drugs (OR 2.05, 95 % CI 1.19-3.52, p < 0.01). Our findings suggest that ATP7B genetic polymorphisms could affect the therapeutic efficacy of platinum-based chemotherapy, and ATP7B gene might be considered as predictive markers for the efficacy evaluation of platinum-based chemotherapy in Chinese Han lung cancer patients.
The description of cryptic species with different pathogenic potentials has changed the perspectives on sporotrichosis. Sporothrix schenckii causes a benign chronic subcutaneous mycosis, Sporothrix brasiliensis is highly virulent, and Sporothrix globosa mainly causes fixed cutaneous lesions. Furthermore, S. brasiliensis is the prevalent species related to cat-transmitted sporotrichosis. Sources of infection, transmission, and distribution patterns also differ between species, and variability differs between species because of different degrees of clonality. The present review article will cover several aspects of the biology of clinically relevant agents of sporotrichosis, including epidemiological aspects of emerging species. Genomic information of Sporothrix spp. is also discussed. The cell wall is an essential structure for cell viability, interaction with the environment, and the host immune cells and contains several macromolecules involved in virulence. Due to its importance, aspects of glycosylation and cell wall polysaccharides are reviewed. Recent genome data and bioinformatics analyses helped to identify specific enzymes of the biosynthetic glycosylation routes, with no homologs in mammalian cells, which can be putative targets for development of antifungal drugs. A diversity of molecular techniques is available for the recognition of the clinically relevant species of Sporothrix. Furthermore, antigens identified as diagnostic markers and putative vaccine candidates are described. Cell-mediated immunity plays a key role in controlling infection, but Sporothrix species differ in their interaction with the host. The adaptive branch of the immune response is essential for appropriate control of infection.