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This study investigates the formation and impact of Endogenous Quasi-Pathogens (EQPs) within cellular environments, focusing on the role of Endogenous Smart Medicine (ESM) as a therapeutic intervention. This work elucidates how induced vibrations facilitate new molecular and atomic connections between adjacent cells, leading to endobiotic bond formation and significantly altered DNA behavior. These vibrations, which dominate cellular processes, induce both temporary and permanent changes in cellular dynamics. The resulting increase in extracellular impedance triggers the emergence of new EQP sources, potentially initiating divergent pathological cycles. Cells experiencing moderate impedance changes are classified as benign, while those with substantial alterations are considered malignant. This study highlights the medical diagnostic implications of EQPs and positions ESM as a precise method for modulating cellular impedance, reducing the effects of EQPs, and potentially treating diseases where disruptions in cellular dynamics and stiffness are critical. Additionally, the integration of ChronoBit Storage (CBS) within ESM introduces a novel energy management mechanism, enhancing therapeutic precision by synchronizing energy distribution with cellular needs. The ChronoVital Index (CVI), a temporal model for assessing time dynamics across biological systems from individual cells to whole organs further refines this approach. By advancing the CVI and CBS, this research paves the way for more sophisticated therapeutic strategies, offering promising applications in the fields of disease management and cellular restoration within the framework of Endogenous Smart Medicine.

Drug development from medicinal plants constitutes an important strategy for finding natural anticancer therapies. While several plant secondary metabolites with potential antitumor activities have been identified, well-defined mechanisms of action remained uncovered. In fact, studies of medicinal plants have often focused on the genome, transcriptome, and proteome, dismissing the relevance of the metabolome for discovering effective plant-based drugs. Metabolomics has gained huge interest in cancer research as it facilitates the identification of potential anticancer metabolites and uncovers the metabolomic alterations that occur in cancer cells in response to treatment. This holds great promise for investigating the mode of action of target metabolites. Although metabolomics has made significant contributions to drug discovery, research in this area is still ongoing. In this review, we emphasize the significance of plant metabolomics in anticancer research, which continues to be a potential technique for the development of anticancer drugs in spite of all the challenges encountered. As well, we provide insights into the essential elements required for performing effective metabolomics analyses.

Glioblastoma multiforme (GBM) is a highly aggressive and fatal primary brain tumor. The resistance of GBM to conventional treatments is attributed to factors such as the blood–brain barrier, tumor heterogeneity, and treatment-resistant stem cells. Current therapeutic efforts show limited survival benefits, emphasizing the urgent need for novel treatments. In this context, natural anti-cancer extracts and especially animal venoms have garnered attention for their potential therapeutic benefits. Bee venom in general and that of the Middle Eastern bee, Apis mellifera syriaca in particular, has been shown to have cytotoxic effects on various cancer cell types, but not glioblastoma. Therefore, this study aimed to explore the potential of A. mellifera syriaca venom as a selective anti-cancer agent for glioblastoma through in vitro and in vivo studies. Our results revealed a strong cytotoxic effect of A. mellifera syriaca venom on U87 glioblastoma cells, with an IC50 of 14.32 µg/mL using the MTT test and an IC50 of 7.49 µg/mL using the LDH test. Cells treated with the bee venom became permeable to propidium iodide without showing any signs of early apoptosis, suggesting compromised membrane integrity but not early apoptosis. In these cells, poly (ADP-ribose) polymerase (PARP) underwent proteolytic cleavage similar to that seen in necrosis. Subsequent in vivo investigations demonstrated a significant reduction in the number of U87 cells in mice following bee venom injection, accompanied by a significant increase in cells expressing caspase-3, suggesting the occurrence of cellular apoptosis. These findings highlight the potential of A. mellifera syriaca venom as a therapeutically useful tool in the search for new drug candidates against glioblastoma and give insights into the molecular mechanism through which the venom acts on cancer cells.

Abstract Patients with coronavirus disease 2019 (COVID-19) were shown to have reduced serum testosterone levels compared to healthy individuals. Low testosterone levels are linked with the development of erectile dysfunction (ED). In this case-controlled study, 20 healthy controls and 39 patients with ED 3 months after recovering from mild-to-moderate COVID-19 pneumonia were studied. The patients ranged in age from 31 to 47 years. To identify early and late COVID-19 infections, real-time polymerase-chain reaction (RT-PCR) and COVID-19 antibody testing were done. The levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), free testosterone (FT), free androgenic index (FAI), and sex hormone-binding globulin (SHBG) were measured. The sexual health inventory for patients (SHIM) score was used to measure the erectile function of the patients and controls. When compared to the controls, the TT serum level in long COVID-19 (LC) patients with ED was low (p = 0.01). In contrast to controls, FT and FAI were both lower in LC patients with ED. (p = 0.001). FSH serum levels did not significantly differ (p = 0.07), but in ED patients, LH serum levels were elevated. SHIM scores were associated with low TT (p = 0.30), FT (p = 0.09), and high LH (p = 0.76) in LC patients with ED. Male patients with decreased serum levels of LH and testosterone may have hypothalamic-pituitary–gonadal axis dysfunction, which could lead to the development of LC-induced ED. Therefore, an in-depth research is necessary to confirm the causal link between COVID-19 and ED in LC patients.

Antimicrobial resistance (AMR) poses a serious global health concern, resulting in a significant number of deaths annually due to infections that are resistant to treatment. Amidst this crisis, antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics (ATBs). These cationic peptides, naturally produced by all kingdoms of life, play a crucial role in the innate immune system of multicellular organisms and in bacterial interspecies competition by exhibiting broad-spectrum activity against bacteria, fungi, viruses, and parasites. AMPs target bacterial pathogens through multiple mechanisms, most importantly by disrupting their membranes, leading to cell lysis. However, bacterial resistance to host AMPs has emerged due to a slow co-evolutionary process between microorganisms and their hosts. Alarmingly, the development of resistance to last-resort AMPs in the treatment of MDR infections, such as colistin, is attributed to the misuse of this peptide and the high rate of horizontal genetic transfer of the corresponding resistance genes. AMP-resistant bacteria employ diverse mechanisms, including but not limited to proteolytic degradation, extracellular trapping and inactivation, active efflux, as well as complex modifications in bacterial cell wall and membrane structures. This review comprehensively examines all constitutive and inducible molecular resistance mechanisms to AMPs supported by experimental evidence described to date in bacterial pathogens. We also explore the specificity of these mechanisms toward structurally diverse AMPs to broaden and enhance their potential in developing and applying them as therapeutics for MDR bacteria. Additionally, we provide insights into the significance of AMP resistance within the context of host–pathogen interactions.

The purpose of this article is to study gloomy eyelet (GE) inside the cell nucleus by using models of warp drive hydro (WDH), swinging spring, Rankine, co-moving reference frame, and Poincare. The beat wave frequency (ω) of blood pressure on the vessel and the swinging spring frequency (Ω) of DNA coincide together on the Rankine model. In this case, it leads to appearing as a sudden pressure drop and an accelerated cavity in the medium of the warp drive hydro (WDH) model. In transient conditions, the vortex flow inside WDH can generate gloomy eyelet (GE), and the tiny distortion of nano space–time revealed inside the gloomy eyelet (GE) inside DNA and the tiny distortion of nano space–time revealed inside the co-moving reference frame (CMRF) model of the gloomy eyelet (GE). The space–time distortion can act as a hidden potential for the cell nucleus and some behaviors of gloomy eyelet can be traced by the frequency responses of human body organs. The interactions between two adjacent different mediums such as the normal cells and abnormal cells, earth’s gravitational effects can lead to changes in the distortion of space–time inside the cell nucleus. Transient bonds between particles can be expected to appear in the gloomy eyelet inside DNA. Identifying the range of changes in the frequency responses and the transient bonds inside the cell nucleus can be introduced as one of the health indicators.

The study of neuroarchitecture is concerned with the significant effects of architecture on human behavior, emotions and thought processes. This review explores the intricate relationship between the brain and perceived environments, focusing on the roles of the anterior cingulate cortex (ACC) and parahippocampal place area (PPA) in processing architectural stimuli. It highlights the importance of mirror neurons in generating empathetic responses to our surroundings and discusses how architectural elements like lighting, color, and space layout significantly impact emotional and cognitive experiences. The review also presents insights into the concept of cognitive maps and spatial navigation, emphasizing the role of architecture in facilitating wayfinding and orientation. Additionally, it addresses how neuroarchitecture can be applied to enhance learning and healing environments, drawing upon principles from the Reggio Emilia approach and considerations for designing spaces for the elderly and those with cognitive impairments. Overall, this review offers a neuroscientific basis for understanding how human cognition, emotions, spatial navigation, and well-being are influenced by architectural design.

In 2020, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) challenged the world with a global outbreak that led to millions of deaths worldwide. Coronavirus disease 2019 (COVID-19) is the symptomatic manifestation of this virus, which can range from flu-like symptoms to utter clinical complications and even death. Since there was no clear medicine that could tackle this infection or lower its complications with minimal adverse effects on the patients’ health, the world health organization (WHO) developed awareness programs to lower the infection rate and limit the fast spread of this virus. Although vaccines have been developed as preventative tools, people still prefer going back to traditional herbal medicine, which provides remarkable health benefits that can either prevent the viral infection or limit the progression of severe symptoms through different mechanistic pathways with relatively insignificant side effects. This comprehensive review provides scientific evidence elucidating the effect of 10 different plants against SARS-CoV-2, paving the way for further studies to reconsider plant-based extracts, rich in bioactive compounds, into more advanced clinical assessments in order to identify their impact on patients suffering from COVID-19.

SARS-CoV-2 triggered a worldwide medical crisis, affecting the world’s social, emotional, physical, and economic equilibrium. However, treatment choices and targets for finding a solution to COVID-19’s threat are becoming limited. A viable approach to combating the threat of COVID-19 is by unraveling newer pharmacological and therapeutic targets pertinent in the viral survival and adaptive mechanisms within the host biological milieu which in turn provides the opportunity to discover promising inhibitors against COVID-19. Therefore, using high-throughput virtual screening, manually curated compounds library from some medicinal plants were screened against four main drivers of SARS-CoV-2 (spike glycoprotein, PLpro, 3CLpro, and RdRp). In addition, molecular docking, Prime MM/GBSA (molecular mechanics/generalized Born surface area) analysis, molecular dynamics (MD) simulation, and drug-likeness screening were performed to identify potential phytodrugs candidates for COVID-19 treatment. In support of these approaches, we used a series of computational modeling approaches to develop therapeutic agents against COVID-19. Out of the screened compounds against the selected SARS-CoV-2 therapeutic targets, only compounds with no violations of Lipinski’s rule of five and high binding affinity were considered as potential anti-COVID-19 drugs. However, lonchocarpol A, diplacol, and broussonol E (lead compounds) were recorded as the best compounds that satisfied this requirement, and they demonstrated their highest binding affinity against 3CLpro. Therefore, the 3CLpro target and the three lead compounds were selected for further analysis. Through protein–ligand mapping and interaction profiling, the three lead compounds formed essential interactions such as hydrogen bonds and hydrophobic interactions with amino acid residues at the binding pocket of 3CLpro. The key amino acid residues at the 3CLpro active site participating in the hydrophobic and polar inter/intra molecular interaction were TYR54, PRO52, CYS44, MET49, MET165, CYS145, HIS41, THR26, THR25, GLN189, and THR190. The compounds demonstrated stable protein–ligand complexes in the active site of the target (3CLpro) over a 100 ns simulation period with stable protein–ligand trajectories. Drug-likeness screening shows that the compounds are druggable molecules, and the toxicity descriptors established that the compounds demonstrated a good biosafety profile. Furthermore, the compounds were chemically reactive with promising molecular electron potential properties. Collectively, we propose that the discovered lead compounds may open the way for establishing phytodrugs to manage COVID-19 pandemics and new chemical libraries to prevent COVID-19 entry into the host based on the findings of this computational investigation.

Scorpion venoms have long captivated scientific researchers, primarily due to the potency and specificity of the mechanism of action of their derived components. Among other molecules, these venoms contain highly active compounds, including antimicrobial peptides (AMPs) and ion channel-specific components that selectively target biological receptors with remarkable affinity. Some of these receptors have emerged as prime therapeutic targets for addressing various human pathologies, including cancer and infectious diseases, and have served as models for designing novel drugs. Consequently, extensive biochemical and proteomic investigations have focused on characterizing scorpion venoms. This review provides a comprehensive overview of the key methodologies used in the extraction, purification, analysis, and characterization of AMPs and other bioactive molecules present in scorpion venoms. Noteworthy techniques such as gel electrophoresis, reverse-phase high-performance liquid chromatography, size exclusion chromatography, and “omics” approaches are explored, along with various combinations of methods that enable bioassay-guided venom fractionation. Furthermore, this review presents four adapted proteomic workflows that lead to the comprehensive dissection of the scorpion venom proteome, with an emphasis on AMPs. These workflows differ based on whether the venom is pre-fractionated using separation techniques or is proteolytically digested directly before further proteomic analyses. Since the composition and functionality of scorpion venoms are species-specific, the selection and sequence of the techniques for venom analyses, including these workflows, should be tailored to the specific parameters of the study.

Buthus occitanus (B. occitanus) is one of the most dangerous scorpions in the world. Despite the involvement of B. occitanus scorpion in severe cases of envenomation in Morocco, no study has focused yet on the proteomic composition of the Moroccan B. occitanus scorpion venom. Mass spectrometry‐based proteomic techniques are commonly used in the study of scorpion venoms. The implementation of top‐down and bottom‐up approaches for proteomic analyses facilitates screening by allowing a global view of the structural aspects of such complex matrices. Here, we provide a partial overview of the venom of B. occitanus scorpion, in order to explore the diversity of its toxins and hereafter understand their effects. To this end, a combination of top‐down and bottom‐up approaches was applied using nano‐high liquid chromatography coupled to nano‐electrospray tandem mass spectrometry (nano‐LC‐ESI MS/MS). The LC‐MS results showed that B. occitanus venom contains around 200 molecular masses ranging from 1868 to 16 720 Da, the most representative of which are those between 5000 and 8000 Da. Interestingly, combined top‐down and bottom‐up LC‐MS/MS results allowed the identification of several toxins, which were mainly those acting on ion channels, including those targeting sodium (NaScTxs), potassium (KScTxs), chloride (ClScTxs), and calcium channels (CaScTx), as well as antimicrobial peptides (AMPs), amphipathic peptides, myotropic neuropeptides, and hypothetical secreted proteins. This study reveals the molecular diversity of B. occitanus scorpion venom and identifies components that may have useful pharmacological activities.

Abstract Introduction While COVID-19 pandemic continues to spread worldwide, researchers have linked patterns of traits to poor disease outcomes. Risk factors for COVID-19 include asthma, elderly age, being pregnant, having any underlying diseases such as cardiovascular disease, diabetes, obesity, and experiencing lifelong systemic racism. Recently, connections to certain genes have also been found, although the susceptibility has not yet been established. We aimed to investigate the available evidence for the genetic susceptibility to COVID-19. Methods This study was a systematic review of current evidence to investigate the genetic susceptibility of COVID-19. By systematic search and utilizing the keywords in the online databases including Scopus, PubMed, Web of Science, and Science Direct, we retrieved all the related papers and reports published in English from December 2019 to September 2020. Results According to the findings, COVID-19 uses the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. Previous studies have shown that people with ACE2 polymorphism who have type 2 transmembrane serine proteases (TMPRSS2) are at high risk of SARS-CoV-2 infection. Also, two studies have shown that males are more likely to become infected with SARS-CoV-2 than females. Besides, research has also shown that patients possessing HLA-B*15:03 genotype may become immune to the infection. Conclusion Combing through the genome, several genes related to immune system’s response were related to the severity and susceptibility to the COVID-19. In conclusion, a correlation was found between the ACE2 levels and the susceptibility to SARS-CoV-2 infection.

Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis in tumours of various cancers. Monoclonal antibodies and nanobodies are one of the potent agents in the treatment of cancer. Due to their high costs, researchers are considering to design and produce peptides as a substitute approach in recent years. The aim of the current study was designing a mimotope against VEGF and evaluate its effects on cell proliferation and tube formation in the HUVEC cell line. For this, a peptide was designed against VEGF and chemically produced. The effects of synthetic peptide and nanobody on the inhibition of proliferation of HUVEC cells were examined using MTT and tube formation assays. The data indicate that the peptide was able to significantly inhibit both HUVEC cell proliferation and tube formation through inhibition of VEGF, highlighting the potential of peptides as a ‘novel’ class of candidate drugs to inhibit angiogenesis.

Abstract Background and Aims Scientists and healthcare workers have expressed their concerns on the impacts of the COVID‐19 pandemic on vaccination coverage in children and adolescents. Therefore, we aimed to systematically review the studies addressing this issue worldwide. Methods We conducted a systematic search of relevant studies using the keywords on databases of PubMed, Web of Science, and Cochrane on May 22, 2021. The identified records were imported into EndNote software and underwent a two‐phase screening process consisting of title/abstract and full‐text screenings against inclusion criteria. The data of the included studies were summarized into a table and the findings were analyzed in a systematic approach. Results From 26 eligible studies, 21 studies demonstrated decreased vaccination rates in the children during the COVID‐19 pandemic, while three studies found increased or no significant changes only in influenza vaccination. The two remaining studies from Brazil and Sweden also showed no significant changes in vaccination rates in the children during the pandemic. Conclusion Most of the reports worldwide reported a decline or delay in vaccination at the time of the COVID‐19 pandemic. A sustained catch‐up program seems to be necessary, especially in low‐income countries, to avoid any vaccine dose missing. Facilitating the vaccination process is recommended, such as decreasing the waiting time for vaccination at the health center, addressing the fear and concerns related to COVID infection for parents, and enhancing vaccine availability, and promoting access in remote areas. Countries should ensure proper vaccination to prevent future pandemics related to vaccine‐preventable diseases.

Abstract Introduction Patients with COVID‐19 may present different viral loads levels. However, the relationship between viral load and disease severity in COVID‐19 is still unknown. Therefore, this study aimed to systematically review the association between SARS‐CoV‐2 viral load and COVID‐19 severity. Methods The relevant studies using the keywords of “COVID‐19” and “viral load” were searched in the databases of PubMed, Scopus, Google Scholar, and Web of Science. A two‐step title/abstract screening process was carried out and the eligible studies were included in the study. Results Thirty‐four studies were included from the initial 1015 records. The vast majority of studies have utilized real‐time reverse transcription‐polymerase chain reaction of the nasopharyngeal/respiratory swabs to report viral load. Viral loads were commonly reported either as cycle threshold (Ct) or log10 RNA copies/ml. Conclusion The results were inconclusive about the relationship between COVID‐19 severity and viral load, as a similar number of studies either approved or opposed this hypothesis. However, the studies denote the direct relationship between older age and higher SARS‐CoV‐2 viral load, which is a known risk factor for COVID‐19 mortality. The higher viral load in older patients may serve as a mechanism for any possible relationships between COVID‐19 viral load and disease severity. There was a positive correlation between SARS‐CoV‐2 viral load and its transmissibility. Nonetheless, further studies are recommended to precisely characterize this matter.

ATP, the power of all cellular functions, is constantly used and produced by cells. The enzyme called ATP synthase is the energy factory in all cells, which produces ATP by adding inorganic phosphate (Pi) to ADP. It is found in the inner, thylakoid and plasma membranes of mitochondria, chloroplasts and bacteria, respectively. Bacterial ATP synthases have been the subject of multiple studies for decades, since they can be genetically manipulated. With the emergence of antibiotic resistance, many combinations of antibiotics with other compounds that enhance the effect of these antibiotics have been proposed as approaches to limit the spread of antibiotic-resistant bacteria. ATP synthase inhibitors, such as resveratrol, venturicidin A, bedaquiline, tomatidine, piceatannol, oligomycin A and N,N-dicyclohexylcarbodiimide were the starting point of these combinations. However, each of these inhibitors target ATP synthase differently, and their co-administration with antibiotics increases the susceptibility of pathogenic bacteria. After a brief description of the structure and function of ATP synthase, we aim in this review to highlight therapeutic applications of the major bacterial ATP synthase inhibitors, including animal’s venoms, and to emphasize their importance in decreasing the activity of this enzyme and subsequently eradicating resistant bacteria as ATP synthase is their source of energy.

Behavioral disorders, such as anxiety and depression, are prevalent globally and touch children and adults on a regular basis. Therefore, it is critical to comprehend how these disorders are affected. It has been demonstrated that neuropeptides can influence behavior, emotional reactions, and behavioral disorders. This review highlights the majority of the findings demonstrating neuropeptides’ behavioral role and functional engineering in depression and anxiety. Gut–brain peptides, hypothalamic releasing hormone peptides, opioid peptides, and pituitary hormone peptides are the four major groups of neuropeptides discussed. Some neuropeptides appear to promote depression and anxiety-like symptoms, whereas others seem to reduce it, all depending on the receptors they are acting on and on the brain region they are localized in. The data supplied here are an excellent starting point for future therapy interventions aimed at treating anxiety and depression.

Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a causative agent of numerous chronic diseases, including caseous lymphadenitis (CLA) in sheep and goats, which has a zoonotic potential in humans in addition to a poor therapeutic response. In this study, out of 120 collected samples, only 12 (10%) were positive for C. pseudotuberculosis by PCR and by intraperitoneal injection of male Guinea pigs and then characterized for antimicrobial susceptibility and its genetic-relatedness by enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR), which showed 2–4 bands ranging from 100 to 3000 bp that can be clustered into four clusters (C1–C4). Despite the serotype biovar 1 only infecting sheep and goats, ERIC–PCR reveals intra-subtyping variation. Examination of affected LNs and organs revealed marked enlargement with either thick creamy green pus or multiple abscesses of variable sizes with a central caseated core surrounded by dense fibrous capsule. A histopathological examination revealed a central necrotic core surrounded by a peripheral mantle of mononuclear cells and a fibrous capsule. Positive immune expression of nuclear factor kappa B (NF-κB/p65) and interleukin-1β (IL-1β) and negative expression of tumor necrosis factor (TNF) in CLA is the first report to our knowledge. Conclusion: In CLA pyogranulomas, IL1β is a more crucial proinflammatory cytokine than TNF in the regulation of C. pseudotuberculosis infection, which is accompanied by marked NF-κB immunoexpression. Therefore, the NF-κB/p65 signaling pathway is involved in the activation of IL1β, and additional immunohistochemical studies are required to determine the various roles of NF-κB/p65 in the inflammatory response within CLA pyogranulomas to control this pathogen.

The present context is a pioneer attempt to verify the ability of copepod, Lernanthropus kroyeri (L. kroyeri), to uptake and accumulate heavy metals. We primarily assess the prevalence of the parasite in various seasons and its clinical signs, as well as post-mortem changes in sea bass (Moron labrax). The morphological features of the parasite using a light microscope, the bioaccumulation of heavy metals in the tissues of both L. kroyeri and M. labrax (gills, muscles) using Flame Atomic Absorption Spectrometry, and the histopathological alterations were monitored. Fish (n = 200) were obtained from Ezbet Elborg and examined for the parasite, L. kroyeri. The results revealed that the total infection was recorded at 86%. The infested fish exhibited excessive mucous and ulceration at the site of attachment. The post-mortem lesion in the gills revealed a marbling appearance with destructed filaments. Various heavy metals (Zn, Co, Cu, and Cd) were detected in the tissues of L. kroyeri and M. labrax and, surprisingly, L. kroyeri had the ability to uptake and accumulate a high amount of Zn in its tissues. Infested fish accumulated a lower concentration of Zn in their tissue compared with the non-infested ones. Within the host tissue, the accumulation of Zn was higher in the gills compared with the muscles. The histopathological findings demonstrated scattered parasitic elements with the destruction of the gill lamellae. Taken together, we highlight the potential role of L. kroyeri to eliminate Zn and it can be utilized as a bio-indicator for metal monitoring studies for sustaining aquaculture.

Genus Angelica is one of the widely distributed and well-known genera of family Umbelliferae. It is utilized mainly by Chinese and Korean populations especially in their folk medicine. Angelica comprises a lot of medicinally important phytoconstituents such as coumarins, furanocoumarins, flavonoids, essential oils, verbascosides, polysaccharides, etc. Members of this genus play important roles, namely antioxidant, anti-inflammatory, anti-microbial, anti-diabetic, skin-whitening, cytotoxic, hepatoprotective, and many others. This review draws attention to many species of genus Angelica with much focus on A. dahurica being one of the highly medicinally used species within this genus.

Lung cancer is the second most commonly diagnosed cancer in the world. In terms of the diagnosis of lung cancer, combination carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) detection had higher sensitivity, specificity, and diagnostic odds ratios than CEA detection alone. Most individuals with elevated serum CA125 levels had lung cancer that was either in stage 3 or stage 4. Serum CA125 levels were similarly elevated in lung cancer patients who also had pleural effusions or ascites. Furthermore, there is strong evidence that human lung cancer produces CA125 in vitro, which suggests that other clinical illnesses outside of ovarian cancer could also be responsible for the rise of CA125. MUC16 (CA125) is a natural killer cell inhibitor. As a screening test for lung and ovarian cancer diagnosis and prognosis in the early stages, CA125 has been widely used as a marker in three different clinical settings. MUC16 mRNA levels in lung cancer are increased regardless of gender. As well, increased expression of mutated MUC16 enhances lung cancer cells proliferation and growth. Additionally, the CA125 serum level is thought to be a key indicator for lung cancer metastasis to the liver. Further, CA125 could be a useful biomarker in other cancer types diagnoses like ovarian, breast, and pancreatic cancers. One of the important limitations of CA125 as a first step in such a screening technique is that up to 20% of ovarian tumors lack antigen expression. Each of the 10 possible serum markers was expressed in 29–100% of ovarian tumors with minimal or no CA125 expression. Therefore, there is a controversy regarding CA125 in the diagnosis and prognosis of lung cancer and other cancer types. In this state, preclinical and clinical studies are warranted to elucidate the clinical benefit of CA125 in the diagnosis and prognosis of lung cancer.

Scorpion venom is a rich source of promising therapeutic compounds, such as highly selective ion channel ligands with potent pharmacological effects. Bot33 is a new short polypeptide of 38 amino acid residues with six cysteines purified from the venom of the Buthus occitanus tunetanus scorpion. Bot33 has revealed less than 40% identity with other known alpha-KTx families. This peptide displayed a neutral amino acid (Leucine), in the position equivalent to lysine 27, described as essential for the interaction with Kv channels. Bot33 did not show any toxicity following i.c.v. injection until 2 µg/kg mouse body weight. Due to its very low venom concentration (0.24%), Bot33 was chemically synthesized. Unexpectedly, this peptide has been subjected to a screening on ion channels expressed in Xenopus laevis oocytes, and it was found that Bot33 has no effect on seven Kv channel subtypes. Interestingly, an in silico molecular docking study shows that the Leu27 prevents the interaction of Bot33 with the Kv1.3 channel. All our results indicate that Bot33 may have a different mode of action from other scorpion toxins, which will be interesting to elucidate.

Litsea glutinosa (L. glutinosa) is considered an evidence-based medicinal plant for the treatment of cancer, the leading cause of death worldwide. In our study, the in vitro antioxidant and in vivo anticancer properties of an essential ethno-medicinal plant, L. glutinosa, were examined using non-toxic doses and a phytochemical analysis was executed using gas-chromatography–mass-spectrometry. The in vitro antioxidant study of the L. glutinosa methanolic extract (LGBME) revealed a concentration-dependent antioxidant property. The bark extract showed promising antioxidant effects in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. The strongest antioxidant activity was demonstrated at the maximum concentration (50 µg/mL). The IC50 values of the LGBME and BHT were 5.51 and 5.01 µg/mL, respectively. At the same concentration, the total antioxidant capacity of the LGBME was 0.161 µg/mL and the ferric reducing antioxidant power assay result of the LGBME was 1.783 µg/mL. In the cytotoxicity study, the LD50 of the LGBME and gallic acid were 24.93 µg/mL and 7.23 µg/mL, respectively. In the in vivo anticancer-activity studies, the LGBME, particularly at a dose of 150 mg/kg/bw, showed significant cell-growth inhibition, decreased tumor weight, increased mean survival rate, and upregulated the reduced hematological parameters in EAC (Ehrlich’s ascites carcinoma)-induced Swiss albino mice. The highest cell-growth inhibition, 85.76%, was observed with the dose of 150 mg/kg/bw. Furthermore, the upregulation of pro-apoptotic genes (p53, Bax) and the downregulation of anti-apoptotic Bcl-2 were observed. In conclusion, LGBME extract has several bioactive phytoconstituents, which confirms the antioxidant and anticancer properties of L. glutinosa.

Coronavirus disease (COVID-19) is a global health challenge, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) triggers a plethora of respiratory disturbances and even multiple organs failure that can be fatal. Nutritional intervention is one of the key components toward to a proper management of COVID-19 patients, especially in those requiring medication, and should thus be considered the first-line treatment. Immuno-modulation and -stimulation are currently being explored in COVID-19 management and are gaining interest by food and pharmaceutical industries. Various dietary combinations, bioactive components, nutrients and fortified foods have been reported to modulate inflammation during disease progression. Dietary combinations of dairy-derived products and eggs are gaining an increasing attention given the huge immunomodulatory and anti-inflammatory properties attributed to some of their chemical constituents. Eggs are complex dietary components containing many essential nutrients and bioactive compounds as well as a high-quality proteins. Similarly, yogurts can replenish beneficial bacteria and contains macronutrients capable of stimulating immunity by enhancing cell immunity, reducing oxidative stress, neutralizing inflammation and regulating the intestinal barriers and gut microbiome. Thus, this review highlights the impact of nutritional intervention on COVID-19 management, focusing on the immunomodulatory and inflammatory effects of immune-enhancing nutrients.

Alzheimer’s disease (AD) was used to describe pre-senile dementia to differentiate it from senile dementia, which develops in the adult age group of more than 65 years. AD is characterized by the deposition of amyloid beta (Aβ) plaque and tau-neurofibrillary tangles (TNTs) in the brain. The neuropathological changes in AD are related to the deposition of amyloid plaques, neurofibrillary tangles, and progression of neuroinflammation, neuronal mitochondrial dysfunction, autophagy dysfunction, and cholinergic synaptic dysfunction. Statins are one of the main cornerstone drugs for the management of cardiovascular disorders regardless of dyslipidemia status. Increasing the use of statins, mainly in the elderly groups for primary and secondary prevention of cardiovascular diseases, may affect their cognitive functions. Extensive and prolonged use of statins may affect cognitive functions in healthy subjects and dementia patients. Statins-induced cognitive impairments in both patients and health providers had been reported according to the post-marketing survey. This survey depends mainly on sporadic cases, and no cognitive measures were used. Evidence from prospective and observational studies gives no robust conclusion regarding the beneficial or detrimental effects of statins on cognitive functions in AD patients. Therefore, this study is a narrative review aimed with evidences to the beneficial, detrimental, and neutral effects of statins on AD.

Acute coronary syndrome (ACS) is a set of signs and symptoms caused by a reduction of coronary blood flow with subsequent myocardial ischemia. ACS is associated with activation of the leukotriene (LT) pathway with subsequent releases of various LTs, including LTB4, LTC4, and LTD4, which cause inflammatory changes and induction of immunothrombosis. LTs through cysteine leukotriene (CysLT) induce activation of platelets and clotting factors with succeeding coronary thrombosis. CysLT receptor (CysLTR) antagonists such as montelukast (MK) may reduce the risk of the development of ACS and associated complications through suppression of the activation of platelet and clotting factors. Thus, this critical review aimed to elucidate the possible protective role of MK in the management of ACS. The LT pathway is implicated in the pathogenesis of atherosclerosis, cardiac hypertrophy, and heart failure. Inhibition of the LT pathway and CysL1TR by MK might be effective in preventing cardiovascular complications. MK could be an effective novel therapy in the management of ACS through inhibition of pro-inflammatory CysLT1R and modulation of inflammatory signaling pathways. MK can attenuate thrombotic events by inhibiting platelet activation and clotting factors that are activated during the development of ACS. In conclusion, MK could be an effective agent in reducing the severity of ACS and associated complications. Experimental, preclinical, and clinical studies are recommended to confirm the potential therapeutic of MK in the management of ACS.

Salmonella continues to be a major threat to public health, especially with respect to strains from a poultry origin. In recent years, an increasing trend of antimicrobial resistance (AMR) in Salmonella spp. was observed due to the misuse of antibiotics. Among the approaches advised for overcoming AMR, probiotics from the Lactobacillus genus have increasingly been considered for use as effective prophylactic and therapeutic agents belonging to the indigenous microbiota. In this study, we isolated lactobacilli from the ilea and ceca of hens and broilers in order to evaluate their potential probiotic properties. Four species were identified as Limosilactobacillusreuteri (n = 22, 45.8%), Ligilactobacillussalivarius (n = 20, 41.6%), Limosilactobacillus fermentum (n = 2, 4.2%) and Lactobacillus crispatus (n = 1, 2%), while three other isolates (n = 3, 6.25%) were non-typable. Eight isolates, including Ligilactobacillussalivarius (n = 4), Limosilactobacillusreuteri (n = 2), L. crispatus (n = 1) and Lactobacillus spp. (n = 1) were chosen on the basis of their cell surface hydrophobicity and auto/co-aggregation ability for further adhesion assays using the adenocarcinoma cell line Caco-2. The adhesion rate of these strains varied from 0.53 to 10.78%. Ligilactobacillussalivarius A30/i26 and 16/c6 and Limosilactobacillus reuteri 1/c24 showed the highest adhesion capacity, and were assessed for their ability to compete in and exclude the adhesion of Salmonella to the Caco-2 cells. Interestingly, Ligilactobacillussalivarius 16/c6 was shown to significantly exclude the adhesion of the three Salmonella serotypes, S. Enteritidis, S. Infantis and S. Kentucky ST 198, to Caco-2 cells. The results of the liquid co-culture assays revealed a complete inhibition of the growth of Salmonella after 24 h. Consequently, the indigenous Ligilactobacillussalivarius 16/c6 strain shows promising potential for use as a preventive probiotic added directly to the diet for the control of the colonization of Salmonella spp. in poultry.

Coronavirus disease 2019 (COVID-19) is primarily caused by various forms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants. COVID-19 is characterized by hyperinflammation, oxidative stress, multi-organ injury (MOI)-like acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Different biomarkers are used in the assessment of COVID-19 severity including D-dimer, ferritin, lactate dehydrogenase (LDH), and hypoxia-inducible factor (HIF). Interestingly, growth differentiation factor 15 (GDF15) has recently become a potential biomarker correlated with the COVID-19 severity. Thus, this critical review aimed to determine the critical association between GDF15 and COVID-19. The perfect function of GDF15 remains not well-recognized; nevertheless, it plays a vital role in controlling cell growth, apoptosis and inflammatory activation. Furthermore, GDF15 may act as anti-inflammatory and pro-inflammatory signaling in diverse cardiovascular complications. Furthermore, the release of GDF15 is activated by various growth factors and cytokines including macrophage colony-stimulating factor (M-CSF), angiotensin II (AngII) and p53. Therefore, higher expression of GDF15 in COVID-19 might a compensatory mechanism to stabilize and counteract dysregulated inflammatory reactions. In conclusion, GDF15 is an anti-inflammatory cytokine that could be associated with the COVID-19 severity. Increased GDF15 could be a compensatory mechanism against hyperinflammation and exaggerated immune response in the COVID-19. Experimental, preclinical and large-scale clinical studies are warranted in this regard.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can trigger the adaptive and innate immune responses, leading to uncontrolled inflammatory reactions and associated local and systematic tissue damage, along with thromboembolic disorders that may increase the risk of acute ischemic stroke (AIS) in COVID-19 patients. The neuropilin (NRP-1) which is a co-receptor for the vascular endothelial growth factor (VEGF), integrins, and plexins, is involved in the pathogenesis of AIS. NRP-1 is also regarded as a co-receptor for the entry of SARS-CoV-2 and facilitates its entry into the brain through the olfactory epithelium. NRP-1 is regarded as a cofactor for binding of SARS-CoV-2 with angiotensin-converting enzyme 2 (ACE2), since the absence of ACE2 reduces SARS-CoV-2 infectivity even in presence of NRP-1. Therefore, the aim of the present study was to clarify the potential role of NRP-1 in COVID-19 patients with AIS. SARS-CoV-2 may transmit to the brain through NRP-1 in the olfactory epithelium of the nasal cavity, leading to different neurological disorders, and therefore about 45% of COVID-19 patients had neurological manifestations. NRP-1 has the potential capability to attenuate neuroinflammation, blood–brain barrier (BBB) permeability, cerebral endothelial dysfunction (ED), and neuronal dysfunction that are uncommon in COVID-19 with neurological involvement, including AIS. Similarly, high NRP-1 serum level is linked with ED, oxidative stress, and the risk of pulmonary thrombosis in patients with severe COVID-19, suggesting a compensatory mechanism to overcome immuno-inflammatory disorders. In conclusion, NRP-1 has an important role in the pathogenesis of COVID-19 and AIS, and could be the potential biomarker linking the development of AIS in COVID-19. The present findings cannot provide a final conclusion, and thus in silico, experimental, in vitro, in vivo, preclinical, and clinical studies are recommended to confirm the potential role of NRP-1 in COVID-19, and to elucidate the pharmacological role of NRP-1 receptor agonists and antagonists in COVID-19.

In recent years, utilization of Rhus coriaria L. (sumac) is upgrading not only in their culinary use and human nutrition, but also in the pharmaceutical industry, food industry and veterinary practices. This is driven by accumulating evidence that support the ethnobotanical use of this plant; in particular, advanced knowledge of the content of nutritional, medicinal and techno-functional bioactive ingredients. Herein, we discuss polyphenolic compounds as the main bioactive ingredients in Rhus coriaria L., which contribute mainly to the significance and utility of this spice. Most of the antioxidant potential and therapeutic roles of sumac are increasingly attributed to its constituent tannins, flavonoids, and phenolic acids. Hydroxyphenyl pyranoanthocyanins and other anthocynins are responsible for the highly desired red pigments accounting for the strong pigmentation capacity and colorant ability of sumac. Certain polyphenols and the essential oil components are responsible for the peculiar flavor and antimicrobial activity of sumac. Tannin-rich sumac extracts and isolates are known to enhance the food quality and the oxidative stability of animal products such as meat and milk. In conclusion, polyphenol-rich sumac extracts and its bioactive ingredients could be exploited towards developing novel food products which do not only address the current consumers’ interests regarding organoleptic and nutritional value of food, but also meet the growing need for ‘clean label’ as well as value addition with respect to antioxidant capacity, disease prevention, and health promotion in humans.

Since its discovery in Wuhan, China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread over the world, having a huge impact on people’s lives and health. The respiratory system is often targeted in people with the coronavirus disease 2019 (COVID-19). The virus can also infect many organs and tissues in the body, including the reproductive system. The consequences of the SARS-CoV-2 infection on fertility and pregnancy in hosts are poorly documented. Available data on other coronaviruses, such as severe acute respiratory syndrome (SARS-CoV) and Middle Eastern Respiratory Syndrome (MERS-CoV) coronaviruses, identified pregnant women as a vulnerable group with increased pregnancy-related complications. COVID-19 was also shown to impact pregnancy, which can be seen in either the mother or the fetus. Pregnant women more likely require COVID-19 intensive care treatment than non-pregnant women, and they are susceptible to giving birth prematurely and having their newborns admitted to the neonatal intensive care unit. Angiotensin converting enzyme 2 (ACE2), a key player of the ubiquitous renin-angiotensin system (RAS), is the principal host cellular receptor for SARS-CoV-2 spike protein. ACE2 is involved in the regulation of both male and female reproductive systems, suggesting that SARS-CoV-2 infection and associated RAS dysfunction could affect reproduction. Herein, we review the current knowledge about COVID-19 consequences on male and female fertility, pregnant women, and their fetuses. Furthermore, we describe the effects of COVID-19 vaccination on reproduction.

The complications following snake bite envenoming are due to the venom’s biological activities, which can act on different systems of the prey. These activities arise from the fact that snake venoms are rich in bioactive molecules, which are also of interest for designing drugs. The venom of Montivipera bornmuelleri, known as the Lebanon viper, has been shown to exert antibacterial, anticancer, and immunomodulatory effects. However, the venom’s activity on the nervous system has not yet been studied, and its effect on the cardiovascular system needs further investigation. Because zebrafish is a convenient model to study tissue alterations induced by toxic agents, we challenged it with the venom of Montivipera bornmuelleri. We show that this venom leads to developmental toxicity but not teratogenicity in zebrafish embryos. The venom also induces neurotoxic effects and disrupts the zebrafish cardiovascular system, leading to heartbeat rate reduction and hemorrhage. Our findings demonstrate the potential neurotoxicity and cardiotoxicity of M. bornmuelleri’s venom, suggesting a multitarget strategy during envenomation.

We analyzed the epitope evolution of the spike protein in 1,860,489 SARS-CoV-2 genomes. The structural dynamics of these epitopes was determined by molecular modeling approaches. The D614G mutation, selected in the first months of the pandemic, is still present in currently circulating SARS-CoV-2 strains. This mutation facilitates the conformational change leading to the demasking of the ACE2 binding domain. D614G also abrogated the binding of facilitating antibodies to a linear epitope common to SARS-CoV-1 and SARS-CoV-2. The main neutralizing epitope of the N-terminal domain (NTD) of the spike protein showed extensive structural variability in SARS-CoV-2 variants, especially Delta and Omicron. This epitope is located on the flat surface of the NTD, a large electropositive area which binds to electronegatively charged lipid rafts of host cells. A facilitating epitope located on the lower part of the NTD appeared to be highly conserved among most SARS-CoV-2 variants, which may represent a risk of antibody-dependent enhancement (ADE). Overall, this retrospective analysis revealed an early divergence between conserved (facilitating) and variable (neutralizing) epitopes of the spike protein. These data aid in the designing of new antiviral strategies that could help to control COVID-19 infection by mimicking neutralizing antibodies or by blocking facilitating antibodies.

COVID-19 has expanded across the world since its discovery in Wuhan (China) and has had a significant impact on people’s lives and health. Long COVID is a term coined by the World Health Organization (WHO) to describe a variety of persistent symptoms after acute SARS-CoV-2 infection. Long COVID has been demonstrated to affect various SARS-CoV-2-infected persons, independently of the acute disease severity. The symptoms of long COVID, like acute COVID-19, consist in the set of damage to various organs and systems such as the respiratory, cardiovascular, neurological, endocrine, urinary, and immune systems. Fatigue, dyspnea, cardiac abnormalities, cognitive and attention impairments, sleep disturbances, post-traumatic stress disorder, muscle pain, concentration problems, and headache were all reported as symptoms of long COVID. At the molecular level, the renin-angiotensin system (RAS) is heavily involved in the pathogenesis of this illness, much as it is in the acute phase of the viral infection. In this review, we summarize the impact of long COVID on several organs and tissues, with a special focus on the significance of the RAS in the disease pathogenesis. Long COVID risk factors and potential therapy approaches are also explored.

With the lack of effective therapy, chemoprevention and vaccination, focusing on the immediate repurposing of existing drugs gives hope of curbing the pandemic. Interestingly, montelukast, a drug usually used in asthma, may be proposed as a potential adjuvant therapy in COVID-19. The aim of the present article was to review the properties of montelukast that could be beneficial in COVID-19. Ten experimentally supported properties were retrieved, either related to SARS-CoV-2 (antiviral properties, prevention of endotheliitis and of neurological disorders linked to SARS-CoV-2), and/or related to the host (improvement of atherogenic vascular inflammation, limitation of the ischemia/reperfusion phenomenon, improvement of respiratory symptoms), and/or related to serious COVID-19 outcomes (limitation of the cytokine storm, mitigation of acute respiratory distress syndrome), and/or related to tissue sequelae (antioxidant properties, anti-fibrosis effects). Based on gathered theoretical evidence, we argue that montelukast should be further tested to prevent and treat COVID-19 outcomes.

The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin–angiotensin system (RAS) in favor of the ACE–angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II–AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the latest insights into the roles of AT1R in COVID-19 outcomes in different systems of the human body, as well as the role of ARBs as tentative pharmacological agents to treat COVID-19.

Cancer is one of the leading causes of mortality in the world. Unfortunately, the present anticancer chemotherapeutics display high cytotoxicity. Accordingly, the discovery of new anticancer agents with lower side effects is highly necessitated. This study aimed to discover an anticancer compound from Hemiscorpius lepturus scorpion venom. Bioactivity-guided chromatography was performed to isolate an active compound against colon and breast cancer cell lines. 2D electrophoresis and MALDI-TOF were performed to identify the molecule. A partial protein sequence was obtained by mass spectrometry, while the full-length was deciphered using a cDNA library of the venom gland by bioinformatics analyses and was designated as leptulipin. The gene was cloned in pET-26b, expressed, and purified. The anticancer effect and mechanism action of leptulipin were evaluated by MTT, apoptosis, and cell cycle assays, as well as by gene expression analysis of apoptosis-related genes. The treated cells displayed inhibition of cell proliferation, altered morphology, DNA fragmentation, and cell cycle arrest. Furthermore, the treated cells showed a decrease in BCL-2 expression and an increase in Bax and Caspase 9 genes. In this study, we discovered a new anticancer protein from H. lepturus scorpion venom. Leptulipin showed significant anticancer activity against breast and colon cancer cell lines.

Antimicrobial peptides constitute one of the most promising alternatives to antibiotics since they could be used to treat bacterial infections, especially those caused by multidrug-resistant pathogens. Many antimicrobial peptides, with various activity spectra and mechanisms of actions, have been described. This review focuses on their use against ESKAPE bacteria, especially in biofilm treatments, their synergistic activity, and their application as prophylactic agents. Limitations and challenges restricting therapeutic applications are highlighted, and solutions for each challenge are evaluated to analyze whether antimicrobial peptides could replace antibiotics in the near future.

In this work, we pursued the biological characterization of the venom of Montivipera bornmuelleri, a viper from the Lebanese mountains. In relation to its antibacterial potential, the inhibitory effect of this venom on the F1F0-ATPase enzymes of Gram-positive Staphylocoocus epidermidis and Gram-negative Escherichia coli bacteria was examined. In order to determine the degree of cytotoxicity of the venom on the HCT116 human colon cancer cell lines, the biological MTT proliferation and cell viability test were implemented. After validation of the enzymatic F1F0-ATPase model by the spectrophotometric method, using quercetin as the reference ligand, results revealed that M. bornmuelleri venom is able to inhibit the activity of the enzyme of these two bacteria with a concentration of the order of 100–150 µg/mL. In addition, a venom concentration of 10 µg/mL was sufficient to kill the totality of HCT116 cell lines cultivated in vitro. These data show that M. bornmuelleri venom is a mixture of diverse molecules presenting activities of interest, and is a potential source to explore in order to discover new drug candidates.

Cardiovascular diseases (CVDs) are considered as a major cause of death worldwide. Therefore, identifying and developing therapeutic strategies to treat and reduce the prevalence of CVDs is a major medical challenge. Several drugs used for the treatment of CVDs, such as captopril, emerged from natural products, namely snake venoms. These venoms are complex mixtures of bioactive molecules, which, among other physiological networks, target the cardiovascular system, leading to them being considered in the development and design of new drugs. In this review, we describe some snake venom molecules targeting the cardiovascular system such as phospholipase A2 (PLA2), natriuretic peptides (NPs), bradykinin-potentiating peptides (BPPs), cysteine-rich secretory proteins (CRISPs), disintegrins, fibrinolytic enzymes, and three-finger toxins (3FTXs). In addition, their molecular targets, and mechanisms of action—vasorelaxation, inhibition of platelet aggregation, cardioprotective activities—are discussed. The dissection of their biological effects at the molecular scale give insights for the development of future snake venom-derived drugs.

Colon carcinogenesis is ranked second globally among human diseases after cardiovascular failures. Bee venom (BV) has been shown to possess in vitro anticancer effects against several types of cancer cells. The two main biopeptides of Apis mellifera BV, namely, melittin (MEL) and phospholipase A2 (PLA2), are suspected to be the biomolecules responsible for the anticancer activity. The present work aims to evaluate the cytotoxic effect of the A. mellifera venom on human colon carcinoma cells (HCT116), and to assess the synergistic effect of MEL and PLA2 on these cells. After analyzing, through high-pressure liquid chromatography, the proportions of MEL and PLA2 on BV, we have established a cell viability assay to evaluate the effect of BV, MEL, PLA2, and a mixture of MEL and PLA2 on the HCT116 cells. Results obtained showed a strong cytotoxicity effect induced by the A. mellifera venom and to a lower extent MEL or PLA2 alone. Remarkably, when MEL and PLA2 were added together, their cytotoxic effect was greatly improved, suggesting a synergistic activity on HCT116 cells. These findings confirm the cytotoxic effect of the A. mellifera venom and highlight the presence of synergistic potential activities between MEL and PLA2, possibly inducing membrane disruption of HCT116 cancer cells. Altogether, these results could serve as a basis for the development of new anticancer treatments.

Breast cancer (BC) is the most common form of cancer among women worldwide. Despite the huge advancements in its treatment, the exact etiology of breast cancer still remains unresolved. There is an increasing interest in the role of the gut microbiome in modulating the anti-cancer therapeutic response. It seems that alteration of the microbiome-derived metabolome potentially promotes carcinogenesis. Taken together, metabolomics has arisen as a fascinating new omics field to screen promising metabolic biomarkers. In this study, fecal metabolite profiling was performed using NMR spectroscopy, to identify potential biomarker candidates that can predict response to neoadjuvant chemotherapy (NAC) for breast cancer. Metabolic profiles of feces from patients (n = 8) following chemotherapy treatment cycles were studied. Interestingly, amino acids were found to be upregulated, while lactate and fumaric acid were downregulated in patients under the second and third cycles compared with patients before treatment. Furthermore, short-chain fatty acids (SCFAs) were significantly differentiated between the studied groups. These results strongly suggest that chemotherapy treatment plays a key role in modulating the fecal metabolomic profile of BC patients. In conclusion, we demonstrate the feasibility of identifying specific fecal metabolic profiles reflecting biochemical changes that occur during the chemotherapy treatment. These data give an interesting insight that may complement and improve clinical tools for BC monitoring.

Hemiscorpius lepturus scorpion stings do not induce considerable pain based on epidemiological surveys conducted in the southwest part of Iran. Accordingly, this study was aimed to identify the analgesic molecule in H. lepturus venom by analyzing a cDNA library of the scorpion venom gland looking for sequences having homology with known animal venom analgesic peptides. The analgesic molecule is a cysteine rich peptide of 55 amino acids. the synthetic peptide was deprotected and refolded. RP-HPLC, Ellman’s, and DLS assays confirmed the refolding accuracy. Circular dichroism (CD) showed helix and beta sheet contents. This peptide, called leptucin, demonstrated 95% analgesic activity at the dose of 0.48 mg/kg in hot plate assay. Leptucin at the doses of 0.32, 0.48, and 0.64 mg/kg showed 100% activity in thermal tail flick test. No hemolysis or cytotoxicity was observed at 8 and 16 μg. Histopathology evaluations indicated no hepatotoxicity, nephrotoxicity, and cardiotoxicity. We thus report that leptucin is the analgesic agent of H. lepturus venom. Regarding the high in vivo efficacy of leptucin and the fact it shows no observable toxicity, it could be suggested as a drug lead in a preclinical study of acute pain as well as the study of its mechanism of action.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of editorials which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...]

Streptomyces is the most frequently described genus of Actinomycetes, a producer of biologically active secondary metabolites. Indeed, the Streptomyces species produces about 70% of antibiotics and 60% of antifungal molecules used in agriculture. Our study was carried out with the goal of isolating and identifying antimicrobial secondary metabolites from Streptomyces misionensis V16R3Y1 isolated from the date palm rhizosphere (southern Tunisia). This strain presented a broad range of antifungal activity against Fusarium oxysporum, Aspergillus flavus, Penicillium expansum, Aspergillus niger, Candida albicans, Candida metapsilosis, and Candida parapsilosis and antibacterial activity against human pathogenic bacteria, including Escherichia fergusonii, Staphylococcus aureus, Salmonella enterica, Enterococcus faecalis, Bacillus cereus and Pseudomonas aeruginosa. The purification procedure entailed ethyl acetate extract, silica gel column, and thin layer chromatography. Based on 1H NMR metabolomic procedure application, also supported by the GC-MS analysis, cyclic dipeptide (l-Leucyl-l-Proline) was identified as the major compound in the bioactive fraction. In order to confirm the identity of the active compound and to have a large quantity thereof, a chemical synthesis of the cyclic dipeptide was performed. The synthetic compound was obtained with a very good yield (50%) and presented almost the same effect compared to the extracted fraction. This study indicates for the first time that Streptomyces misionensis V16R3Y1 exhibits a broad spectrum of antimicrobial activities, produced cyclic dipeptide (l-Leucyl-l-Proline) and might have potential use as a natural agent for pharmaceutical and agri-food applications.

The inappropriate or excessive use of antimicrobial agents caused an emerging public health problem due to the resulting resistance developed by microbes. Therefore, there is an urgent need to develop effective antimicrobial strategies relying on natural agents with different mechanisms of action. Nature has been known to offer many bioactive compounds, in the form of animal venoms, algae, and plant extracts that were used for decades in traditional medicine. Animal venoms and secretions have been deeply studied for their wealth in pharmaceutically promising molecules. As such, they were reported to exhibit many biological activities of interest, such as antibacterial, antiviral, anticancer, and anti-inflammatory activities. In this review, we summarize recent findings on the antimicrobial activities of crude animal venoms/secretions, and describe the peptides that are responsible of these activities.