Lethal Properties Research Articles

WHEN CLIMATE CHANGES, SO DOES VIOLENCE: EXAMINING THE LINK BETWEEN WEATHER AND CRIME IN PERNAMBUCO-NORTHEAST, BRAZIL

This paper examines the impact of weather shocks on crime in Pernambuco-Northeast, one of the states most affected by climate disasters in the Brazilian semi-arid region. We show that precipitation and temperature shocks in the form of droughts have a significant impact on the increase of rates of intentional lethal violent crimes (ILVC), property crimes (PC), and homicides. The effects of precipitation fluctuations in the form of droughts persist beyond the agricultural season and in the medium-term, and vary according to municipal and criminological characteristics. Moreover, adverse weather conditions (e.g., droughts) have a greater impact on income-related crimes. Consistent with this evidence, we find that the persistent response of crime rates to adverse weather conditions is driven by negative shocks to rural income, followed by a deterioration in overall economic activity, urban labor market conditions, and the government’s ability to provide public goods. The patterns we identify align with a relationship between weather and crime explained by reduced opportunity costs associated with criminal activity. Regarding policy recommendations, our findings suggest that local governments should prioritize investments in water infrastructure, agricultural irrigation, expansion of water coverage, and conservation of forested areas. These measures can contribute to climate adaptation and mitigate the economic impact of weather shocks on crime.

Evaluation of candidate monovalent Bitis arietans antivenom using eggs from hyperimmunized layer chickens in Zaria Kaduna State, Nigeria

Aim: This research sought to experiment on a cheaper alternative to snake antivenom production using hyperimmunized chicken eggs. Methods: Twenty-two Swiss albino mice were used to determine the median lethal dose (LD50) and lethality neutralization assay. Twenty-layer chickens, aged 17-weeks-old were divided into two groups of 10 chickens each. Based on body weight, group A were hyperimmunized with 1/5th LD50 of crude Bitis arietans venom in adjuvant (Montanide™ ISA 201) at two-weeks interval over eight-weeks period; while group B were administered normal saline. Using polyethylene glycol 6000, immunoglobulin Y was extracted from 15 pooled egg yolks. Twelve Wistar rats were used for the haemorrhagic and anti-haemorrhagic assays. The haemolytic activity of the venom and anti-haemolytic effect of the candidate antivenom was determined in vitro using caprine erythrocytes. Results: The LD50 of the pooled Bitis arietans venom was 0.9 mg/kg. Agar gel immunodiffusion test confirmed the presence of precipitin antibodies in the candidate antivenom. EchiTab plus-ICP® neutralized lethal effect of all dilutions and the stock (10 mg/ml) venom of Bitis arietans while the candidate antivenom was limited to 3log2 dilution of the stock venom (1.25 mg/ml). In the haemorrhagic assay the venom exhibited haemorrhagic activity at 2.5, 5 and 10 mg/ml and the highest anti-haemorrhagic activity of the candidate antivenom at 10mg/ml. The candidate antivenom exhibited significantly higher (p < 0.05) anti-haemolytic activity against the venom of Bitis arietans at 10 mg/ml. Conclusion: The antibodies have inhibitory properties against the lethal, haemorrhagic and haemolytic properties of Bitis arietans venom.

ANALYSIS OF INFECTIOUS MEDICAL WASTE MANAGEMENT IMPLICATION ON SUSTAINABLE AGRICULTURE DURING THE COVID-19 PANDEMIC - CASE STUDY OF ŠUMADIJA DISTRICT (REPUBLIC OF SERBIA)

Agriculture is the world’s most important industry. According to the structure, Šumadija district is mainly composed of arable land and gardens, which make up 69%. The increased amount of COVID-19 waste generated from medical activities in rural areas needs to be properly handled due to its contagious, even lethal properties. The aim of this study is an analysis of two drivers through the generation of COVID-19 waste, Central and local treatment site, proposed transport routes, and total cost in Šumadija district. Results showed the economic costs of transportation increased 2.5 times compared to before and after the emergence of the COVID-19 pandemic. Also, the increase in health risk was correlated to the increase in the per capita cost of transportation along the transportation routes. Analyses of human health risks and detailed financial calculations gave a clear insight in infectious waste management possible influence on agriculture.

Pyrethrins Profiles and Contents in Seedlings, in Vitro Cultures, and Acclimatized Plants of Tanacetum cinerariifolium Clones (Asteraceae)

Tanacetum cinerariifolium (Trevir.) Sch. Bip., Asteraceae, known as pyrethrum, is a perennial herb endemic to the eastern Adriatic coast. It is cultivated worldwide for its valuable secondary metabolites: pyrethrins, which are natural insecticides. Pyrethrins are monoterpene esters of chrysanthemum acid (Pyrethrin-I, Cinerin-I, Jasmolin-I) or pyrethric acid (Pyrethrin-II, Cinerin-II, Jasmolin-II) with lethal or knock-down insecticidal properties, respectively. The market demand of pyrethrin-based products is increasing due to the organic farming requirements. In the present study the content of pyrethrins was determined by GC/MS in n-hexane extracts of shoots of several in vitro clones and in flower heads of outdoor acclimatized plants from the same clones during primary and secondary blooming, as well as in seedlings grown on different soil types. Statistical analyses were done by One-way ANOVA Post Hoc LSD analysis. All pyrethrins were detected in all samples, including a Pyrethrin-I isomer but they differed in content and proportion. As expected, pyrethrins in in vitro shoots and in seedlings were in small amounts. However, in the flower heads of the acclimatized plants, pyrethrin content was comparable to that of the native Dalmatian populations. The main component in all samples was Pyrethrin-I, possessing the strongest insecticidal activity, with the highest content in the flower heads of the primary flowering: 4.87 mg/g with a CV of 24.9%. Statistical differences were noted between clones for Pyrethrin-II and the Pyrethrin-I isomer in June samples, and Pyrethrin-I in September samples (p < 0.05). A wide range of variation was also found in seedlings due to different soil types. Growing conditions should be optimized in terms of sunlight and watering, and further research on pyrethrin content should be carried out in several consecutive years.

Oxidative biotransformation of organophosphotioate pesticides and acetylcholinesterase enzymatic inhibition

Introduction: Pesticides have lethal properties, capable of controlling or eliminating a living organism; they block the organisms' vital metabolic processes. They cause serious problems for human health, as they are highly toxic. The most used pesticides that are considered toxic are known as organophosphothioates (OP/P=S) in their commercialized form and organophosphates (OP/P=O) in their active form. These compounds have been the subject of studies on their metabolism and toxicology. According to research, these pesticides' toxicity is increased when oxidative metabolic desulfurization reactions occur, with the P=S bond being transformed into a P=O bond. This toxicity is due to the ability of OP/P=O species to inhibit the human acetylcholinesterase enzyme (HssAChE). Methods: To study the oxidative biotransformation of OP/P=S pesticides and the inhibition of the HssAChE enzyme by OP/P=S and OP/P=O using the molecular docking technique and QM/MM calculations. Results: The theoretical results showed that parathion is the compound with the greatest capacity to transform its P=S bonds into P=O bonds, thus forming the active paraoxon metabolite in the oxidative biotransformation process. In the HssAChE inhibition by OP/P=S and OP/P=O, our results showed that of all the compounds investigated, those with the highest inhibitory activities are parathion, paraoxon, malathion, diazoxon, chlorpyrifos and omethoate. Conclusion: This study was essential due to the lack of information in the literature about the oxidative biotransformation process of OP/P=S pesticides and the ability of these compounds to inhibit HssAChE. With this study, it was possible to observe that, in the oxidative biotransformation, chlorpyrifos and parathion have greater capacities to transform into their active metabolites and in the inhibition of the HssAChE enzyme, it was possible to observe that not all OF/P=O are the ones with the highest abilities to inhibit the HssAChE enzyme.

Recent Progress in the Decapod Iridescent Virus 1 Study

Decapod iridescent virus 1 (DIV1), also known as shrimp hemocyte iridescent virus or Cherax quadricarinatus iridovirus, has received extensive attention in recent years due to its highly contagious and lethal properties in crustaceans. In 2019, the Executive Committee of the International Committee on Taxonomy of Viruses approved DIV1 as a new species of the new genus Decapodiridovirus in the family Iridoviridae. To gain a more comprehensive understanding of DIV1, this review summarizes recent advances in DIV1 research, including classification, detection techniques, clinical symptoms, infection mechanisms, and host immune responses. A deeper understanding of the interaction between DIV1 and the host has potentially important implications for developing effective antiDIV1 strategies.

A Cell-Fate Reprogramming Strategy Reverses Epithelial-to-Mesenchymal Transition of Lung Cancer Cells While Avoiding Hybrid States.

Network modeling unravels the highly complex and plastic process regulating epithelial and mesenchymal states in cancer cells and discovers therapeutic interventions for reversing epithelial-to-mesenchymal transition and enhancing chemosensitivity.

Lethal Effects of Imergard WP, a Perlite-based Dust, on Amblyomma americanum (Ixodida: Ixodidae) Larvae and Nymphs.

As resistance in economically and medically important ixodids (hard ticks, Ixodida: Ixodidae) to conventional synthetic toxin-based acaricides has become increasingly widespread, research efforts to identify alternative control tactics have intensified. Laboratory bioassays on the lone star tick, Amblyomma americanum (L.), as a model for other ixodid species, were conducted to assess the efficiency of Imergard WP perlite-based dust versus CimeXa, a silica gel-based insecticidal product that is highly effective against ixodid larvae and nymphs. Each of the two inert desiccant dusts immobilized A. americanum larvae and nymphs within 4-6 h, and killed 100% of the ixodids by 24 h after contact by brief immersion in dry dusts, and after they crawled ≈7.3 cm across a filter paper disc treated with the dusts. Contact by crawling on a dried aqueous film of the dusts, however, did not immobilize and kill the ixodids by 24 h. Similar to silica gel-based desiccant dust, dry perlite-based Imergard WP dust might prophylactically protect cattle and other animals from medically and agriculturally important ixodid pests. Perlite can potentially be stored indefinitely, it can retain its lethal properties for as long as adequate amounts remain on a substrate, and it might be acceptable for limited application in environmentally sensitive habitats.

Nanoemulsified Formulation of Cedrela odorata Essential Oil and Its Larvicidal Effect against Spodoptera frugiperda (J.E. Smith).

Cedrela odorata L. is a plant species from the Meliaceae family that is cultivated for timber production. Although the C. odorata essential oil (EO) contains mainly sesquiterpenes, its insecticidal potential is unknown. The lipophilic properties and high degradation capacity of EOs have limited their application for use in pest control. However, the currently available knowledge on the nanoemulsification of EOs, in addition to the possibility of improving their dispersion, would allow them to prolong their permanence in the field. The objective of the present work was to develop a nanoemulsion of the C. odorata EO and to evaluate its larvicidal activity against Spodoptera frugiperda. The EO was obtained by the hydrodistillation of C. odorata dehydrated leaves, and the nanoemulsion was prepared with non-ionic surfactants (Tween 80 and Span 80) using a combined method of agitation and dispersion with ultrasound. The stability of the nanoemulsion with a droplet diameter of <200 nm was verified in samples stored at 5 °C and 25 °C for 90 days. Both the C. odorata EO and its corresponding nanoemulsion presented lethal properties against S. frugiperda. The results obtained provide guidelines for the use of wood waste to produce sustainable and effective insecticides in the fight against S. frugiperda. In addition, considering that a phytochemical complex mixture allows the simultaneous activation of different action mechanisms, the development of resistance in insects is slower.

Reduced IL-37 gene expression and CD8 T lymphocytes in patients with metastatic breast cancer

The exact immunopathological mechanisms in the progression of breast cancer are not clearly understood, but various factors including CD8 T lymphocytes have lethal properties on tumor cells. On the other hand, interleukin-37 (IL-37), as a new member of the IL-1 family, is an anti-inflammatory cytokine. The exact role of IL-37 in breast cancer has not yet been determined. This study aimed to evaluate the CD8 T lymphocytes count and IL-37 gene expression in newly diagnosed breast cancer patients with and without metastasis. In this study, blood samples from 36 metastatic and 36 non-metastatic breast cancer patients and 36 healthy individuals as control were collected. After RNA extraction and cDNA synthesis, the relative gene expression was performed using real-time PCR. Also, counting the CD8 T lymphocytes was done by flow cytometry technique. The results of this study showed that the gene expression of IL-37 in blood samples of metastatic and non-metastatic breast cancer patients was significantly lower than in healthy individuals (P &lt; 0.05). The relative gene expression of the IL-37 in ER+/PR+/HER2+ patients with non-metastatic breast cancer had a significant increase compared to HER2+ patients (P &lt; 0.05). Also, CD8 T lymphocytes count in the samples of patients including non-metastatic and metastatic breast cancer was significantly decreased compared to the healthy individuals (P &lt; 0.05). Our findings provide evidence that IL-37 gene expression and CD8 T lymphocytes count, significantly decreased in non-metastatic and metastatic breast cancer. Considering the possible effects of IL-37 on TCD8 cells in tumor immune responses, more research will be done to benefit from the therapeutic effects of this cytokine in the future.

Synthesis of Silver Nanoparticles of Plant Extract Pistaciaatlantica and Their Antibacterial Effects on Antibiotic Resistant Strains of S. Aureus

Aims In recent years, the synthesis of nanoparticles (Ag-NPs) by plants has been done on a larger scale because it is faster and cheaper. There is also an increase in pathogenicity caused by antibiotic-resistant Staphylococcus aureus. In this study, the biosynthesis of silver nanoparticles by using an extract of mountain pistachio (Pistaciaatlantica) and its antimicrobial properties have been reported. Methods &amp; Materials The extract of Pistaciaatlantica as the reducing agent was used for the biosynthesis of silver nanoparticles. The formation of nanoparticles was confirmed using a spectrophotometer (UV). The resulting nanoparticles were analyzed to determine the Z-Average (d.nm) and the dispersion index (PDI) of the nanoparticles using dynamic light scattering (DLS) and its inhibitory activity and lethality (MBC) against Staphylococcus aureus (S. aureus) were investigated. The diameter of the aura of bacterial growth was also measured. Findings The UV-Vis spectrum shows an absorption band of about 350-450 nm, which represents the biological Ag nanoparticles. Size and morphological properties of nanoparticles were performed by DLS which show that hydrodynamic diameter (Z-Average) is 1132 nm and PDI number is 0.373, indicating a uniform particle size distribution and nanoparticle stability. The inhibitory and lethal properties of Pistaciaatlantica nanoparticles on S. aureus species (PTCC 1764) are 12.5 micrograms per milliliter. Also, the diameter of the halo of bacterial growth is 12 mm which was observed at a concentration of 1000 μg/mL. Conclusion Pistaciaatlantica bio-silver nanoparticles had good antimicrobial activity against S. aureus

Antimicrobial Activity of Mentha piperita, Rosmarinus officinalis, and Withania somnifera Prepared by Ultrasound Against Escherichia coli Isolated from Poultry Stool

Background: Extraction by conventional methods such as Soxhlet requires a long time and the possibility of damage to heat-sensitive compounds. Objectives: In this study, modern ultrasound methods used to perform and investigate the antibacterial properties of plant extracts were compared. Methods: The extracts of Mentha piperita, Rosmarinus officinalis, and Withania somnifera were prepared by an ultrasound device. Ten Escherichia coli strains were isolated from poultry stool samples. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) plant extracts against E. coli were determined using the microdilution method. Results: The results showed that the lowest inhibitory concentrations of rosemary, peppermint, and wind cheese extracts prepared by ultrasound were equal to 3.1 mg/mL, while the highest inhibitory concentrations of these extracts were equal to 25, 25, and 50 mg/mL, respectively. The lowest lethal concentrations of rosemary, peppermint, and wind cheese extracts were 6.25 mg/mL, while the highest inhibitory concentrations of these extracts were 25, 25, and 50 mg/mL, respectively. The lowest bactericidal concentrations of rosemary, peppermint, and wind cheese extracts prepared by ultrasonic waves were equal to 6.25 mg/mL, while the highest lethal concentrations of these extracts were equal to 50, 25, and 100 mg/mL, respectively. Conclusions: According to the findings of the study, it can be concluded that the use of ultrasonic waves is a fast, effective, and economical method for extracting plant components. In addition, the methanolic extract of peppermint has the most inhibitory and lethal properties.

To Evaluate The Pernicious Histological Changes Of the Thickness Of Purkinje Cell Layer After Lithium Carbonate Ingestion

Background: The human cerebellum consists of two lobes and each cerebellar hemisphere consists of Gray and white matter. The gray matter has outermost layer called Molecular cell layer, the middle layer composed of Purkinje cell and innermost is Granular cell layer. In the Molecular layer are Stellate, Basket and Dendrites of Purkinje cells. The middle layer presented the characteristic pyramidal shaped Purkinje cells. Aim: To evaluate and record morphological data of the thickness of purkinje cells layer in normal Control group A and in group B rodents which were given lithium carbonate so as to prove the lethal property of the anti-depressive drug lithium carbonate on the histology of Purinje cells layer of cerebellar cortex. Method: Ten albino rats were given lithium carbonate for a period of six weeks and then micrometry was carried out for both groups. Results: The data which was obtained in both groups was analyzed and it was concluded that the Clinicians and population should be aware of the deleterious effects of lithium carbonate. Conclusion: Our study defined the consequences and the sequele of using Lithium carbonate by patients suffering from psychosis as Lithium can cause toxicity even at therapeutic doses. Keywords: Micrometry, deleterious, rhombencephalon

Reduced IL-37 gene expression and CD8T lymphocytes in patients with metastatic breast cancer.

The exact immunopathological mechanisms in the progression of breast cancer are not clearly understood, but various factors including CD8 T lymphocytes have lethal properties on tumor cells. On the other hand, interleukin-37 (IL-37), as a new member of the IL-1 family, is an anti-inflammatory cytokine. The exact role of IL-37 in breast cancer has not yet been determined. This study aimed to evaluate the CD8T lymphocytes count and IL-37 gene expression in newly diagnosed breast cancer patients with and without metastasis. In this study, blood samples from 36 metastatic and 36 non-metastatic breast cancer patients and 36 healthy individuals as control were collected. After RNA extraction and cDNA synthesis, the relative gene expression was performed using real-time PCR. Also, counting the CD8T lymphocytes was done by flow cytometry technique. The results of this study showed that the gene expression of IL-37 in blood samples of metastatic and non-metastatic breast cancer patients was significantly lower than in healthy individuals (P <0.05). The relative gene expression of the IL-37 in ER+/PR+/HER2+ patients with non-metastatic breast cancer had a significant increase compared to HER2+ patients (P <0.05). Also, CD8T lymphocytes count in the samples of patients including non-metastatic and metastatic breast cancer was significantly decreased compared to the healthy individuals (P <0.05). Our findings provide evidence that IL-37 gene expression and CD8T lymphocytes count, significantly decreased in non-metastatic and metastatic breast cancer. Considering the possible effects of IL-37 on TCD8 cells in tumor immune responses, more research will be done to benefit from the therapeutic effects of this cytokine in the future.

Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia

ABSTRACT Mycobacterium tuberculosis strains of the early ancient sublineage of the Beijing genotype are mostly drug susceptible and mainly circulate in East Asia. We have recently discovered two clusters of this sublineage emerging in the Asian part of Russia (VNTR-defined 1071-32 and 14717-15 types) and, to our surprise, both were strongly MDR/XDR-associated. Here, we evaluated their pathogenic features. The clinical isolates and reference laboratory strain H37Rv were investigated in the C57BL/6 mouse model to assess their virulence and lethality properties. The BACTEC MGIT 960 system was used to study the in vitro growth characteristics. In the murine model, strains 396 (14717-15-cluster, from Buryatia, Far East) and 6691 (1071-32-cluster, from Omsk, Siberia) demonstrated contrasting properties. The 396-infected group had significantly higher mortality, more weight loss, higher bacterial burden, and more severe lung pathology. Furthermore, compared to the previously published data on other Russian epidemic Beijing strains (B0/W148, CAO, Central Asian Russian), strain 396 demonstrated the highest mortality. Under the in vitro growth experiment, cluster 14717-15 isolates had significantly shorter lag-phase. To conclude, low-virulent MDR strain 6691 belongs to the Beijing 1071-32-cluster widespread across FSU countries but at low prevalence. This corresponds to common expectation that multiple drug resistance mutations reduce fitness and virulence. In contrast, highly lethal and hypervirulent MDR strain 396 represents an intriguing Beijing 14717-15 cluster predominant only in Buryatia, Far East (16%), sporadically found beyond it, but not forming clusters of transmission. Further in-depth study of this most virulent Russian Beijing cluster is warranted.

Physicochemical Characteristics of Four Limonene-Based Nanoemulsions and Their Larvicidal Properties against Two Mosquito Species, Aedes albopictus and Culex pipiens molestus.

Simple SummaryThe repeated use of synthetic insecticides against mosquitoes has posed negative impacts on the environment; hence, the utilization of more ecofriendly mosquito control products is deemed necessary. Nanoformulations of phytochemical substances with a safer profile for the environment have been considered potential larvicidal agents against mosquitoes. In this perspective, we formulated 4 (R)-(+)-limonene based oil-in-water nanoemulsions by low and high energy methods, and we studied their physicochemical characteristics (e.g., viscosity, stability, mean droplet diameter, polydispersity index). In addition, we evaluated their larvicidal properties against two mosquito species of great medical importance, Culex pipiens molestus and Aedes albopictus. Laboratory bioassays showed that limonene-based nanoemulsions either improved or did not affected limonene toxicity, depending on the delivery system and mosquito species. In conclusion, all tested limonene-based nanoemulsions provided sufficient toxic effects against mosquito larvae, serving as potential formulations for mosquito control applications.Negative impacts on the environment from the continuous use of synthetic insecticides against mosquitoes has driven research towards more ecofriendly products. Phytochemicals, classified as low-risk substances, have been recognized as potential larvicides of mosquitoes; however, problems related to water solubility and stability are limiting factors for their use in mosquito control programs in the field. In this context, many researchers have focused on formulating essential oils in nanoemulsions, exploiting innovative nanotechnology. In the current study, we prepared 4 (R)-(+)-limonene oil-in-water nanoemulsions using low and high energy methods, and we evaluated their physicochemical characteristics (e.g., viscosity, stability, mean droplet diameter, polydispersity index) and their bioactivity against larvae of two mosquito species of great medical importance, namely, Cx. pipiens molestus and Ae. albopictus. According to the dose–response bioassays with the limonene-based nanoemulsions and pure limonene (dissolved in organic solvent), the tested nanoformulations improved the activity of limonene against Ae. albopictus larvae, while the performance of limonene was either the same or better than limonene against Cx. pipiens molestus, depending on the applied system. Overall, we achieved the production of limonene-based delivery nanosystems, with sufficient lethal properties against mosquito larvae to consider them promising larvicidal formulations applicable to mosquito breeding sites.

Cloning of hok gene into anhydrotetracycline inducible pASK75 vector reveals potent antimicrobial effect of 19 amino acid long N-terminal fragment of hok peptide.

An important toxin-antitoxin (TA) system hok/sok, encoded by R1 plasmid of Escherichia coli, is involved in the post segregation killing of cells that have lost the plasmid. The lethal properties of hok protein have been utilized for the environmental containment of microbes and the development of potential vaccine candidates. This study aimed to demonstrate the potent anti-microbial property of a 19 amino acid (AA) long N-terminal fragment of hok peptide. This was accomplished by designing a conditional suicide system based on hok gene expression cloned in an anhydrotetracycline (aTc) inducible vector - pASK75. Heat shock and electroporation were utilized for the transformation of Escherichia coli and Vibrio cholerae cells, respectively. The minimal induction concentration (MId C) of aTc, determined by analyzing the expression of green fluorescent protein cloned separately into pASK75 vector, was 30 ng/mL. As hok gene was synthesized de novo (using recombinant polymerase chain reaction) in our study, various random sized hok fragments were generated (as a result of the error-prone nature of Taq polymerase). The smallest hok fragment able to bring about effective antimicrobial killing was a 19 AA long N-terminal fragment of hok having the wild type sequence, except for the carboxy terminus AA residue. The MId C of aTc in our experiments was 6-fold lower than previously reported, making our bacterial clones suitable for use in mammalian systems as potential vaccine candidates. Based on our experiments, we hypothesize the 19 AA long N-terminal fragment of hok peptide to be the smallest possible hok fragment sufficient to bring about effective antimicrobial killing.

Anti-diabetic activity of Iphiona aucheri leaf extract

The methanolic extract of Iphiona aucheri leaves and its n-hexane, chloroform and aqueous fractions were screened for phytochemicals, cytotoxic effects, total phenolic contents, antioxidant and anti-diabetic properties. The methanolic extract was assessed for its in vivo anti-diabetic effects. The results indicated the presence of alkaloid, protein and amino acids, carbohydrates, glycosides, flavonoids, and saponins along with the highest brine shrimp lethality (90.7 ± 1.8%), α-amylase inhibition (60.2%) and free radical scavenging properties. The diabetic control indicated a significant (p&lt;0.05) decrease in weight and high-density lipoprotein and elevated level of blood glucose, bilirubin, creatinine, urea, triglyceride, low density lipoprotein, very low-density lipoprotein, transaminases, and alkaline phosphatase. All these changes were restored significantly (p&lt;0.05) by treatment of diabetic rats with methanolic extract of I. aucheri. The results show the potential of I. aucheri as a source of therapeutic compounds against diabetic, hyperlipidemia and free radical associated disorders.

Torin2 Exploits Replication and Checkpoint Vulnerabilities to Cause Death of PI3K-Activated Triple-Negative Breast Cancer Cells.

Frequent mutation of PI3K/AKT/mTOR signaling pathway genes in human cancers has stimulated large investments in targeted drugs but clinical successes are rare. As a result, many cancers with high PI3K pathway activity, such as triple-negative breast cancer (TNBC), are treated primarily with chemotherapy. By systematically analyzing responses of TNBC cells to a diverse collection of PI3K pathway inhibitors, we find that one drug, Torin2, is unusually effective because it inhibits both mTOR and other PI3K-like kinases (PIKKs). In contrast to mTOR-selective inhibitors, Torin2 exploits dependencies on several kinases for S-phase progression and cell-cycle checkpoints, thereby causing accumulation of single-stranded DNA and death by replication catastrophe or mitotic failure. Thus, Torin2 and its chemical analogs represent a mechanistically distinct class of PI3K pathway inhibitors that are uniquely cytotoxic to TNBC cells. This insight could be translated therapeutically by further developing Torin2 analogs or combinations of existing mTOR and PIKK inhibitors.

Kratom: Implications for Health Care Providers

Kratom is an herbal drug originating from the Mitragyna speciosa, a plant indigenous to Southeast Asia. Kratom has been widely used for its stimulant and opioid-like effects derived from its main psychoactive alkaloid properties mitragynine and 7-hydroxymitragynine. In the United States, kratom is gaining popularity as an herbal and natural dietary supplement, as well as a natural and legal alternative to narcotics. Kratom use is typically accompanied by increasing tolerance and dependence making it highly problematic. Kratom's potentially toxic and lethal properties have become an emerging public health threat. Due to deficiencies of governmental controls and its rising prevalence among individuals who ingest kratom, health care providers need to be familiar with the pharmacology, adverse effects, and problems associated with kratom ingestion when caring for individuals. [Journal of Psychosocial Nursing and Mental Health Services, 57(12), 15-20.].