Resveratrol-Loaded Polydimethylsiloxane-Silica Hybrid Materials: Synthesis, Characterization, and Antitumoral Activity.

In this work, hybrid materials within the polydimethylsiloxane-silica (PDMS-SiO2) system, synthesized via the sol-gel method, were developed and characterized for their potential to incorporate and release the bioactive compound resveratrol (RES). RES was incorporated into the materials with a high loading efficiency (>75%) using the rotary evaporator technique. This incorporation induced the amorphization of RES, resulting in enhanced solubility and in vitro release when compared to the free polyphenolic compound. The release profiles displayed pH dependence, exhibiting notably faster release at pH 5.2 compared to pH 7.4. The gradual release of RES over time demonstrated an initial time lag of approximately 4 h, being well described by the Weibull model. In vitro cytotoxicity studies were conducted on human osteosarcoma cells (MG-63), revealing a concentration-dependent decrease in cell viability for RES-loaded samples (for concentrations >50 µg mL-1).

Telangiectatic osteosarcoma in four dogs: Cytologic, histopathologic, cytochemical, and immunohistochemical findings.

Telangiectatic osteosarcoma is a rare variant of osteosarcoma histologically and clinically similar to hemangiosarcoma (HSA). This case series describes the imaging and cytologic features of four histologically confirmed telangiectatic osteosarcomas, including the use of cytochemical stains. Alkaline phosphatase (ALP) was applied to Wright-Giemsa-stained cytology slides, and Factor VIII immunohistochemistry was evaluated. Cytologic characteristics included atypical mesenchymal cells with evidence of acute and chronic hemorrhage. Telangiectatic osteosarcoma cases had positive ALP cytochemical staining, while control HSA cases were negative. Factor VIII immunohistochemistry was negative in telangiectatic osteosarcoma and positive in HSA. Cytologic diagnosis of telangiectatic osteosarcoma with positive ALP cytochemical staining can help differentiate this neoplasm from HSA.

Biopesticide Turex®'s cytotoxicity, genotoxicity and cell cycle arrest on HepG2 cell line.

Population growth leads to the need for more efficient techniques and compounds in agriculture, such as pesticides, to deal with the ever-growing demand. Pesticides may end up in the environment, often compromising the ecosystem affecting all organisms including humans. Therefore, the consequences of exposure to these compounds to biota and humans needs to be assessed. Bearing this in mind, the aim of this study was to examine the in vitro cytotoxicity and genotoxicity attributed to exposure to the biopesticide Turex® utilizing the liver cell line HepG2. Cells were incubated with biopesticide Turex® at 250, 500, 1000, 1500 or 2000 µg/L in both non-activated and activated forms for 24 and 48 h. Subsequent effects on cell viability were assessed using the MTT. The influence on cell cycle dynamics was determined by flow cytometry, while DNA damage was measured by the comet assay. Data demonstrated that activated Turex® induced cytotoxicity and DNA damage after 48 h in HepG2 cell line. The cell cycle progression was not markedly affected by Turex® at any concentration or duration of exposure. In conclusion, data demonstrated the potential adverse effects attributed to exposure to biopesticide Turex® in human cell line HepG2. Consequently, this type of biopesticide needs to be further investigated to determine the potential adverse in vivo effects on various non-target organisms.

Cytotoxic effects of Chartergellus communis wasp venom peptide against melanoma cells.

Cancer is a huge public health problem being one of the main causes of death globally. Specifically, melanoma is one of the most threatening cancer types due to the metastatic capacity, treatment resistance and mortality rates. It is evident the urgent need for research on new agents with pharmacological potential for cancer treatment, in order to develop new cancer therapeutic strategies and overcome drug resistance. The present work investigated the anti-tumoral potential of Chartergellus-CP1 peptide, isolated from Chartergellus communis wasp venom on human melanoma cell lines with different pigmentation degrees, namely the amelanotic cell line A375 and pigmented cell line MNT-1. Chartergellus-CP1 induced selective cytotoxicity to melanoma cell lines when compared to the lower induced cytotoxicity towards to nontumorigenic keratinocytes. Chartergellus-CP1 peptide induced apoptosis in both melanoma cell lines, cell cycle impairment in amelanotic A375 cells and intracellular ROS increase in pigmented MNT-1 cells. The amelanotic A375 cell line showed higher sensitivity to the peptide than the pigmented cell line MNT-1. From our knowledge, this is the first study reporting the cytotoxic effects of Chartergellus-CP1 on melanoma cells.

Magnetic Chitosan Bionanocomposite Films as a Versatile Platform for Biomedical Hyperthermia.

Responsive magnetic nanomaterials offer significant advantages for innovative therapies, for instance, in cancer treatments that exploit on-demand delivery on alternating magnetic field (AMF) stimulus. In this work, biocompatible magnetic bionanocomposite films are fabricated from chitosan by film casting with incorporation of magnetite nanoparticles (MNPs) produced by facile one pot synthesis. The influence of synthesis conditions and MNP concentration on the films' heating efficiency and heat dissipation are evaluated through spatio-temporal mapping of the surface temperature changes by video-thermography. The cast films have a thickness below 100 µm, and upon exposure to AMF (663 kHz, 12.8 kA m-1 ), induce exceptionally strong heating, reaching a maximum temperature increase of 82 °C within 270 s irradiation. Further, it is demonstrated that the films can serve as substrates that supply heat for multiple hyperthermia scenarios, including: i) non-contact automated heating of cell culture medium, ii) heating of gelatine-based hydrogels of different shapes, and iii) killing of cancerous melanoma cells. The films are versatile components for non-contact stimulus with translational potential in multiple biomedical applications.

CETP Expression in Bone-Marrow-Derived Cells Reduces the Inflammatory Features of Atherosclerosis in Hypercholesterolemic Mice.

CETP activity reduces plasma HDL-cholesterol concentrations, a correlate of an increased risk of atherosclerotic events. However, our recent findings suggest that CETP expression in macrophages promotes an intracellular antioxidant state, reduces free cholesterol accumulation and phagocytosis, and attenuates pro-inflammatory gene expression. To determine whether CETP expression in macrophages affects atherosclerosis development, we transplanted bone marrow from transgenic mice expressing simian CETP or non-expressing littermates into hypercholesterolemic LDL-receptor-deficient mice. The CETP expression did not change the lipid-stained lesion areas but decreased the macrophage content (CD68), neutrophil accumulation (LY6G), and TNF-α aorta content of young male transplanted mice and decreased LY6G, TNF-α, iNOS, and nitrotyrosine (3-NT) in aged female transplanted mice. These findings suggest that CETP expression in bone-marrow-derived cells reduces the inflammatory features of atherosclerosis. These novel mechanistic observations may help to explain the failure of CETP inhibitors in reducing atherosclerotic events in humans.

Tyrosine-Mutant AAV8 Vector Mediated Efficient and Safe Gene Transfer of Pigment Epithelium-Derived Factor to Mouse Lungs.

BACKGROUND/AIMS: Recombinant adeno-associated viruses (rAAV) are an important tool for lung targeted gene therapy. Substitution of tyrosine with phenylalanine residues (Y-F) in the capsid have been shown to protect the AAV vector from ubiquitin/proteasome degradation, increasing transduction efficiency. We tested the mutant Y733F-AAV8 vector for mucus diffusion, as well as the safety and efficacy of pigment epithelium-derived factor (PEDF) gene transfer to the lung. METHODS: For this purpose, Y733F-AAV8-PEDF (1010 viral genome) was administered intratracheally to C57BL/6 mice. Lung mechanics, morphometry, and inflammation were evaluated 7, 14, 21, and 28 days after injection. RESULTS: The tyrosine-mutant AAV8 vector was efficient at penetrating mucus in ex vivo assays and at transferring the gene to lung cells after in vivo instillation. Increased levels of transgene mRNA were observed 28 days after vector administration. Overexpression of PEDF did not affect in vivo lung parameters. CONCLUSION: These findings provide a basis for further development of Y733F-AAV8-based gene therapies for safe and effective delivery of PEDF, which has anti-angiogenic, anti-inflammatory and anti-fibrotic activities and might be a promising therapy for lung inflammatory disorders.

CETP expression ameliorates endothelial function in female mice through estrogen receptor-α and endothelial nitric oxide synthase pathway.

Endothelial dysfunction is an early manifestation of atherosclerosis. The cholesteryl ester transfer protein (CETP) has been considered proatherogenic by reducing plasma HDL levels. However, CETP may exhibit cell- or tissue-specific effects. We have previously reported that male mice expressing the human CETP gene show impaired endothelium-mediated vascular relaxation associated with oxidative stress. Although sexual dimorphisms on the metabolic role of CETP have been proposed, possible sex differences in the vascular effects of CETP were not previously studied. Thus, here we investigated the endothelial function of female CETP transgenic mice as compared with nontransgenic controls (NTg). Aortas from CETP females presented preserved endothelium-dependent relaxation to acetylcholine and an endothelium-dependent reduction of phenylephrine-induced contraction. eNOS phosphorylation (Ser1177) and calcium-induced NO levels were enhanced, whereas reactive oxygen species (ROS) production and NOX2 and SOD2 expression were reduced in the CETP female aortas. Furthermore, CETP females exhibited increased aortic relaxation to 17ß-estradiol (E2) and upregulation of heat shock protein 90 (HSP90) and caveolin-1, proteins that stabilize estrogen receptor (ER) in the caveolae. Indeed, CETP females showed an increased E2-induced relaxation in a manner sensitive to estrogen receptor-α (ERα) and HSP90 inhibitors methylpiperidinopyrazole (MPP) and geldanamycin, respectively. MPP also impaired the relaxation response to acetylcholine in CETP but not in NTg females. Altogether, the study indicates that CETP expression ameliorates the anticontractile endothelial effect and relaxation to E2 in females. This was associated with less ROS production, and increased eNOS-NO and E2-ERα pathways. These results highlight the need for considering the sex-specific effects of CETP on cardiovascular risk.NEW & NOTEWORTHY Here we demonstrated that CETP expression has a sex-specific impact on the endothelium function. Contrary to what was described for males, CETP-expressing females present preserved endothelium-dependent relaxation to acetylcholine and improved relaxation response to 17ß-estradiol. This was associated with less ROS production, increased eNOS-derived NO, and increased expression of proteins that stabilize estrogen receptor-α (ERα), thus increasing E2-ERα signaling sensitivity. These results highlight the need for considering the sex-specific effects of CETP on cardiovascular risk.

Multiple biliary duct hamartomas in a cat resulting in a hepatic mass: A case report.

A 13-year-old, male neutered domestic short-haired cat was diagnosed with multiple biliary duct hamartomas after liver lobectomy for a suspected malignant hepatic mass. Distinguishing ultrasonographic findings included a lobular, mostly well-defined, heterogeneous, predominantly hyperechoic, left hepatic mass. Computed tomography (CT) confirmed the presence of a lobular, well-defined, fluid to soft tissue attenuating, heterogeneously hypoenhancing left divisional hepatic mass. Grossly, a large left sided multilobular pale pink gelatinous hepatic mass was surgically excised. Histopathologically, the mass was composed of irregular cystic spaces lined by cuboidal epithelium and separated by mature regular fibrous tissue. Three months following surgery there was no evidence of recurrence or progression of disease on repeat abdominal ultrasound (AUS).

Morin Hydrate Encapsulation and Release from Mesoporous Silica Nanoparticles for Melanoma Therapy.

Melanoma incidence, a type of skin cancer, has been increasing worldwide. There is a strong need to develop new therapeutic strategies to improve melanoma treatment. Morin is a bioflavonoid with the potential for use in the treatment of cancer, including melanoma. However, therapeutic applications of morin are restrained owing to its low aqueous solubility and limited bioavailability. This work investigates morin hydrate (MH) encapsulation in mesoporous silica nanoparticles (MSNs) to enhance morin bioavailability and consequently increase the antitumor effects in melanoma cells. Spheroidal MSNs with a mean size of 56.3 ± 6.5 nm and a specific surface area of 816 m2/g were synthesized. MH was successfully loaded (MH-MSN) using the evaporation method, with a loading capacity of 28.3% and loading efficiency of 99.1%. In vitro release studies showed that morin release from MH-MSNs was enhanced at pH 5.2, indicating increased flavonoid solubility. The in vitro cytotoxicity of MH and MH-MSNs on human A375, MNT-1 and SK-MEL-28 melanoma cell lines was investigated. Exposure to MSNs did not affect the cell viability of any of the cell lines tested, suggesting that the nanoparticles are biocompatible. The effect of MH and MH-MSNs on reducing cell viability was time- and concentration-dependent in all melanoma cell lines. The A375 and SK-MEL-28 cell lines were slightly more sensitive than MNT-1 cells in both the MH and MH-MSN treatments. Our findings suggest that MH-MSNs are a promising delivery system for the treatment of melanoma.

Survival of severely compromised endodontically treated teeth restored with or without a fiber glass post

Abstract Objective The use of a fiber glass post (FGP) type and choice of FGP diameter to restore endodontically treated incisors without ferrule is controversial. This study evaluated survival rate and failure mode of severely compromised central incisors without ferrule rehabilitated using resin-based composite (RBC) with or without FGP with different diameters. Methodology A total of 60 decoronated bovine incisors without a ferrule were endodontically treated and prepared for 1.4, 1.6, and 1.8 mm diameter FGPs (Whitepost System DC 0.5, Fit 0.4, and DCE 0.5; FGM). Half of the teeth received FGPs cemented using dual-cure resin cement (Allcem Core; FGM), the other half were filled using only bulk-fill RBC (OPUS Bulk Fill; FGM). The crowns were directly restored with RBC. The roots were embedded in polystyrene resin and the periodontal ligament was simulated with polyether impression material. Fatigue testing was conducted under 5 Hz cyclic loading at 30 degrees to the incisal edge, beginning at 50 N (5,000 cycles) as a warmup. After, the load was increased 100 N every 15,000 cycles until fracture occurred. All specimens were subjected to transillumination, micro-CT analysis, and digital radiography before and after fatigue testing. Fracture mode was classified according to severity and repair potential. Data were analyzed with Kaplan-Meier survival test and post hoc log-rank test (α=0.05) for pairwise comparisons. Results Using FGP significantly increased the number of cycles to failure, irrespective of FGP diameters (p=0.001). The FGP diameters had no statistically significant effect on cycles to failure or failure mode. Conclusion Using FGP without ferrule improved survival rate of structurally severely compromised central incisors compared with rehabilitation without FGP. The diameter of the FGPs had no effect on the survival rate and failure mode.

Drug Delivery Systems and Flavonoids: Current Knowledge in Melanoma Treatment and Future Perspectives.

Melanoma is an aggressive form of skin cancer with a high prevalence in the population. An early diagnosis is crucial to cure this disease. Still, when this is not possible, combining potent pharmacological agents and effective drug delivery systems is essential to achieve optimal treatment and improve patients' quality of life. Nanotechnology application in biomedical sciences to encapsulate anticancer drugs, including flavonoids, in order to enhance therapeutic efficacy has attracted particular interest. Flavonoids have shown effectiveness against various types of cancers including in melanoma, but they show low aqueous solubility, low stability and very poor oral bioavailability. The utilization of novel drug delivery systems could increase flavonoid bioavailability, thereby potentiating its antitumor effects in melanoma. This review summarizes the potential of different flavonoids in melanoma treatment and the several nanosystems used to improve their biological activity, considering published information that reported improved biological and pharmacological properties of encapsulated flavonoids.

Antitumoral potential of Chartergellus-CP1 peptide from Chartergellus communis wasp venom in two different breast cancer cell lines (HR+ and triple-negative).

Breast cancer represents the most incident cancer in women. Surgery, chemotherapy, radiation therapy, and hormone therapy remain the main treatment for this type of cancer. However, increasing resistance to anti-cancer drugs through poor response for some types of breast cancer to treatments highlights the need to develop new therapeutic agents to fight the disease. In this study, we evaluated the anti-tumor potential of the Chartergellus-CP1 peptide isolated from the wasp venom of Chartergellus communis in human breast cancer cell lines MCF-7 (HR+) and MDA-MB-231 (triple-negative). Cells viability, morphology, cell cycle dynamics, reactive oxygen species (ROS) production, and apoptosis were assessed for both cell lines after exposure to Chartergellus-CP1 during 24 and 48 h. The results showed that Chartergellus-CP1 led to a significant increase of cells in the S phase in addition to a high generation of ROS (being more evident in the MCF-7 cell line) associated with apoptotic cell death. This work demonstrates, for the first time, the cytotoxic effects of Chatergellus-CP1 on human breast cancer cell lines including cell cycle profile, oxidative stress generation, and cell death mechanisms.

Lymph node yield in the pathological staging of resected nonmetastatic colon cancer: The more the better?

INTRODUCTION: Guidelines recommend regional lymphadenectomy with a lymph node yield (LNY) of at least 12 lymph nodes (LN) for adequate colon cancer (CC) staging. LNY ≥22LN may improve survival, especially in right-sided CC [Lee et al., Surg Oncol, 27(3), 2018]. This multicentric retrospective cohort study evaluated the impact of LNY and tumor laterality on CC staging and survival. MATERIALS AND METHODS: Patients with stage I-III CC that underwent surgery from 2012 to 2018 were grouped according to LNY: <22 and ≥ 22. Primary outcomes were LN positivity (N+ rate) and disease-free survival (DFS). Overall survival (OS) was the secondary outcome. Exploratory analyses were performed for laterality and stage. RESULTS: We included 795 patients (417 < 22LN, 378 ≥ 22LN); 53% had left-sided CC and 29%/37%/38% had stage I/II/III tumors. There was no association between LNY ≥22LN and N+ rate after adjustment for grade, T stage, lymphovascular invasion (LVI) and perineural invasion; a trend for a higher N+ rate in left-sided CC was identified (interaction p = 0.033). With a median follow-up of 63.6 months for DFS and 73.2 months for OS, 254 patients (31.9%) relapsed and 207 (26.0%) died. In multivariate analysis adjusted for age, ASA score, laparoscopic approach, T/N stage, mucinous histology, LVI and adjuvant chemotherapy, LNY ≥22LN was significantly associated with both DFS (HR 0.75, p = 0.031) and OS (HR 0.71, p = 0.025). Restricted cubic spline analysis showed a more significant benefit for right-sided CC. CONCLUSION: LNY ≥22LN was associated with longer DFS and OS in patients with operable CC, especially for right-sided CC.

Aggressive Colorectal Cancer in an Inflammatory Bowel Disease Patient following Treatment with Vedolizumab: A Case Report.

Introduction: The increased risk of bowel cancer in patients with inflammatory bowel disease can be related with the extent, duration and severity of inflammation or with the cancer immune surveillance interference of immunosuppressive drugs used in inflammatory bowel disease treatment. Therefore, the risk-benefit ratio associated with long-term therapeutic strategies should be based on the patient's age, sex, comorbidities and disease phenotype. Case Report: We present the case of a 76-year-old man with a history of melanoma stage Clark III and steroid-dependent left-sided colitis, refractory to mesalamine and thiopurines, with a diagnosis of a multifocal colorectal adenocarcinoma shortly after clinical and endoscopic remission 1 year after starting vedolizumab. Discussion: Vedolizumab is a gut-selective monoclonal anti-α4ß7-integrin antibody that inhibits lymphocyte migration into the gastrointestinal submucosa. Its effectiveness for induction and maintenance of remission and its favorable safety profile make it an alternative in patients with chronic refractory colitis and contraindications to anti-TNF-α. However, there is the hypothesis that, by reducing the migration of activated leukocytes to the gastrointestinal tract, it may also reduce immunosurveillance, increasing the colorectal malignancy risk in the long term. More studies are necessary to address this issue.

Introdução: O aumento do risco de neoplasias intestinais em doentes com doença inflamatória intestinal correlacionase com a extensão, duração e gravidade de inflamação assim como com o potencial efeito na vigilância imunitária associado aos fármacos imunossupressores utilizados no seu tratamento. Por isso, a avaliação do risco-benefício da utilização de estratégias terapêuticas a longo prazo deve basear-se no género, idade, comorbilidades e fenótipo da doença. Caso clínico: Os autores apresentam o caso de um homem de 76 anos com história pregressa de melanoma maligno estadio Clark III e colite ulcerosa esquerda cortico-dependente e refratária à terapêutica convencional, com o diagnóstico de um adenocarcinoma colo-rectal um ano após ter iniciado terapêutica com vedolizumab e ter atingido remissão clínica e endoscópica. Discussão: O vedolizumab é um anticorpo anti-integrina α4ß7 que inibe a migração dos linfócitos para a submucosa gastrointestinal. A sua eficácia na indução e manutenção da remissão e o seu perfil de segurança tornam-no uma boa alternativa em doentes com doença refratária e contraindicações para anti-TNF-α. Contudo, ao diminuir a migração dos leucócitos para o trato gastrointestinal, poderá reduzir a imunovigilância, aumentando o risco de neoplasia colo-rectal. No entanto, este é ainda um conceito teórico, sendo necessários mais estudos que o comprovem.

Combined Therapy with Dacarbazine and Hyperthermia Induces Cytotoxicity in A375 and MNT-1 Melanoma Cells.

Melanoma is a drug-resistant cancer, representing a serious challenge in cancer treatment. Dacarbazine (DTIC) is the standard drug in metastatic melanoma treatment, despite the poor results. Hyperthermia has been proven to potentiate chemotherapy. Hence, this work analyzed the combined action of hyperthermia and DTIC on A375 and MNT-1 cell lines. First, temperatures between 40 °C and 45 °C were tested. The effect of DTIC on cell viability was also investigated after exposures of 24, 48, and 72 h. Then, cells were exposed to 43 °C and to the respective DTIC IC10 or IC20 of each time exposure. Overall, hyperthermia reduced cell viability, however, 45 °C caused an excessive cell death (>90%). Combinational treatment revealed that hyperthermia potentiates DTIC's effect, but it is dependent on the concentration and temperature used. Also, it has different mechanisms from the treatments alone, delaying A375 cells at the G2/M phase and MNT-1 cells at the S and G2/M phases. Intracellular reactive oxygen species (ROS) levels increased after treatment with hyperthermia, but the combined treatment showed no additional differences. Also, hyperthermia highly increased the number of A375 early apoptotic cells. These results suggest that combining hyperthermia and DTIC should be more explored to improve melanoma treatment.

Pro-inflammatory polarization of macrophages is associated with reduced endoplasmic reticulum-mitochondria interaction.

Macrophages play a role in host defense, tissue remodeling and inflammation. Different inflammatory stimuli drive macrophage phenotypes and responses. In this study we investigated the relationship between macrophages immune phenotype and mitochondrial bioenergetics, cell redox state and endoplasmic reticulum (ER)-mitochondria interaction. Bacterial lipopolysaccharide (LPS) and interferon-γ (IFNγ) pro-inflammatory stimuli decreased oxidative metabolism (basal, phosphorylating and maximal conditions) and increased baseline glycolysis (117%) and glycolytic capacity (43%) in THP-1 macrophages. In contrast, interleukin-4 (IL4) and interleukin-13 (IL13) anti-inflammatory stimuli increased the oxygen consumption rates in baseline conditions (21%) and associated with ATP production (19%). LPS + IFNγ stimuli reduced superoxide anion levels by accelerating its conversion into hydrogen peroxide (H2O2) while IL4+IL13 decreased H2O2 release rates. The source of these oxidants was extra-mitochondrial and associated with increased NOX2 and SOD1 gene expression. LPS + IFNγ stimuli decreased ER-mitochondria contact sites as measured by IP3R1-VDAC1 interaction (34%) and markedly upregulated genes involved in mitochondrial fusion (9-10 fold, MFN1 and 2) and fission (∼7 fold, DRP1 and FIS1). Conversely, IL4+IL13 stimuli did not altered ER-mitochondria interactions nor MFN1 and 2 expression. Together, these results unveil ER-mitochondria interaction pattern as a novel feature of macrophage immunological, metabolic and redox profiles.

The Development of Smoked Mackerel with Reduced Sodium Content.

The World Health Organization recommends reducing salt (sodium chloride, NaCl) intake by 30% by 2025. Since smoked fish can deliver up to 4 g NaCl/100 g, the aim of this study was to develop safe, healthy and attractive smoked chub mackerel (Scomber japonicus) with a reduced NaCl content. Two brines (5% and 10%) were used with different ratios of NaCl and potassium chloride (KCl). In each brine, 0%, 25%, 50% and 75% of NaCl was replaced by KCl, resulting in 1.3, 1.1, 0.9 and 0.6 g NaCl (5% brine), and 2.6, 2.0, 1.2 and 0.8 g NaCl (10% brine) per 100 g, respectively. Similar yield, nutritional, safety, texture and colour properties were found in most formulations. The most desirable taste attributes (negligible bitterness and adequate saltiness) were obtained with a 5% brine prepared with 75% NaCl + 25% KCl. Such conditions seemed to allow for obtaining an attractive product for conscious consumers.

Venom of Viperidae: A Perspective of its Antibacterial and Antitumor Potential.

The emergence of multi-drug resistant bacteria and limitations on cancer treatment represent two important challenges in modern medicine. Biological compounds have been explored with a particular focus on venoms. Although they can be lethal or cause considerable damage to humans, venom is also a source rich in components with high therapeutic potential. Viperidae family is one of the most emblematic venomous snake families and several studies highlighted the antibacterial and antitumor potential of viper toxins. According to the literature, these activities are mainly associated to five protein families - svLAAO, Disintegrins, PLA2, SVMPs and C-type lectins- that act through different mechanisms leading to the inhibition of the growth of bacteria, as well as, cytotoxic effects and inhibition of metastasis process. In this review, we provide an overview of the venom toxins produced by species belonging to the Viperidae family, exploring their roles during the envenoming and their pharmacological properties, in order to demonstrate its antibacterial and antitumor potential.