Search

Aedes aegypti L. is the major vector of the arboviruses responsible for dengue fever, one of the most devastating human diseases. Some bacterial, fungal and plant metabolites belonging to different chemical subgroups, including Amaryllidaceae alkaloids, anthracenes, azoxymethoxytetrahydropyrans, cytochalasans, 2,5-diketopiperazines, isochromanones, naphthoquinones, organic small acids and their methyl esters, sterols and terpenes including sesquiterpenes and diterpenes, were tested for their larvicidal and adulticidal activity against Ae. aegypti. Out of 23 compounds tested, gliotoxin exhibited mosquitocidal activity in both bioassays with an LC50 value of 0.0257 ± 0.001 µg/µL against 1st instar Ae. aegypti and LD50 value of 2.79 ± 0.1197 µg/mosquito against adult female Ae. aegypti. 2-Methoxy-1,4-naphthoquinone and cytochalasin A showed LC50 values of 0.0851 ± 0.0012 µg/µL and 0.0854 ± 0.0019 µg/µL, respectively, against Ae. aegypti larvae. In adult bioassays, fusaric acid (LD50= 0.8349 ± 0.0118 µg/mosquito), 3-nitropropionic acid (LD50 = 1.6641 ± 0.0494 µg/mosquito) and α-costic acid (LD50 = 2.547 ± 0.0835 µg/mosquito) exhibited adulticidal activity. Results from the current study confirm that compounds belonging to cytochalsin, diketopiperazine, naphthoquinone and low molecular weight organic acid groups are active and may stimulate further SAR investigations.

Abstract Sphaeropsidins are iso-pimarane diterpenes produced by phytopathogenic fungi that display promising anticancer activities. Sphaeropsidin A, in particular, has been shown to counteract regulatory volume increase, a process used by cancer cells to avoid apoptosis. This study reports the hemi-synthesis of new lipophilic derivatives obtained by modifications of the C15,C16-alkene moiety. Several of these compounds triggered severe ER swelling associated with strong proteasomal inhibition and consequently cell death, a feature that was not observed with respect to mode of action of the natural product. Significantly, an analysis from the National Cancer Institute sixty cell line testing did not reveal any correlations between the most potent derivative and any other compound in the database, except at high concentrations (LC50). This study led to the discovery of a new set of sphaeropsidin derivatives that may be exploited as potential anti-cancer agents, notably due to their maintained activity towards multidrug resistant models.

Abstract Among microorganisms, fungi are the ones that have the most imagination in producing secondary metabolites with the most varied structural differences, which are produced through different biosynthetic pathways. Therefore, they synthesize secondary metabolites classifiable into numerous families of natural compounds such as amino acids, alkaloids, anthraquinones, aromatic compounds, cyclohexene epoxides, furanones, macrolides, naphthoquinones, polyketides, pyrones, terpenes, etc. They also produced metabolites with very complex structures that can not be classified in the known families of natural compounds. Many fungal metabolites show different biological activities with potential applications in agriculture, food chemistry, cosmetics, pharmacology and medicine. This review is focused on the fungal secondary metabolites with anticancer activity isolated in the last ten years. For some metabolites, when described, their biosynthetic origin, the mode of action and the results of structure activity relationships studies are also reported. Graphical Abstract

The increase in the world population, which will be almost 10 billion by 2050, will require considerable efforts to significantly increase food production. Despite the considerable progress made in agriculture, this need is becoming an emergency due to desertification, environmental pollution and climate changes. Biotic stresses, such as pathogenic bacteria and fungi, primarily contribute to significant losses in agricultural productivity and compromise food safety. These harmful agents are predominantly managed using large quantities of synthetic pesticides. However, this widespread use has led to substantial environmental pollution, increased pest resistance and toxic residues in agricultural produce, which subsequently enter the food supply, posing severe health risks to humans and animals. These challenges have significantly driven the advancement of integrated pest management strategies to reduce or eliminate synthetic pesticides. A practical and viable alternative lies in biopesticides—methods developed from natural products that are safe for human and animal health. This approach aligns with the strong demand from consumers and public authorities for safer pest control solutions. This review was focused on the isolation, chemical and biological characterization of natural products for the biocontrol of phytopathogenic bacteria and, in some cases, fungi with potential eco-friendly applications.

Background: More than half of patients with Parkinson’s disease will experience psychosis symptoms in the form of hallucinations or delusions at some point over the course of their disease. These symptoms can significantly impact patients’ health-related quality of life, cognitive abilities, and activities of daily living (ADLs) and function. Clinical assessment of how psychosis impacts these measures is crucial; however, few studies have assessed this sufficiently, in part due to a lack of appropriate scales for comprehensively assessing function. Objective: The objective was to assess how symptoms of Parkinson’s disease psychosis (PDP) impact ADLs and function, cognitive function, and health-related quality of life. Design: To address this unmet need, we utilized a modified version of the Functional Status Questionnaire (mFSQ) to measure the impact of psychosis on ADLs and function in patients with PDP treated with pimavanserin, a US Food and Drug Administration-approved medication to treat hallucinations and delusions associated with PDP. Methods: Eligible patients entered a 16-week, single-arm, open-label study of oral pimavanserin (34 mg) taken once daily. The primary endpoint was change from baseline to Week 16 on the mFSQ. Secondary endpoints included the Movement Disorders Society–modified Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) I and II; Schwab and England ADL; Clinical Global Impression–Severity of Illness (CGI-S), Clinical Global Impression–Improvement (CGI-I), and Patient Global Impression–Improvement (PGI-I), and were also measured as change from baseline to Week 16 using mixed-effects model for repeated measures (MMRM) and least-squares mean (LSM). Results: Our results in a proof-of-concept, 16-week, open-label clinical study in 29 patients demonstrated that an improvement in psychosis symptoms following treatment with pimavanserin was associated with improvements in multiple measures of ADLs and function. Notably, a significant improvement was found on the primary endpoint, change from baseline to Week 16 in mFSQ score [LSM [SE] 14.0 [2.50], n = 17; 95% CI (8.8, 19.3); p

Plain Language summary In Rwanda, youth who are having sex use family planning less than married women. This study involved asking family planning providers and adults what they think about youth using family planning. Data for this study was collected in 2018, and included 32 interviews with adult family planning users and eight group discussions with family planning providers in two areas of Rwanda. The findings show that Rwandans believe youth should not have sex before they are married. Family planning providers do provide youth with services; however, they often push stopping sexual activity, offer a smaller selection of family planning methods, and exaggerate risks associated with sex and family planning use. Family planning providers support youth by honoring their need for privacy, keeping their secrets, and providing fast services so fewer people see them at the clinic. Providers like to help adolescents in youth corners, which are special spaces within health facilities just for youth. Importantly, adult women who use family planning want youth in their community to be able to use family planning, too. In order to respond to the issues raised, the Rwandan government can start conversations in villages and more broadly about the need for youth to have access to family planning. The government should also teach family planning providers and anyone who comes into contact with youth to offer helpful and friendly services. Setting up spaces for adults to talk with family planning providers about youth access to family planning could also contribute to fewer barriers to services for adolescents.

Lampedusa, the largest island of the Pelagie archipelago, Sicily, Italy, has proven to be a rich source of plants and shrubs used in folk medicine. These plants, often native to the island, have been very poorly investigated for their phytochemical composition and biological potential to be translated into pharmacological applications. To start achieving this purpose, a specimen of Limonium lopadusanum, a plant native to Lampedusa, was investigated for the first time. This manuscript reports the results of a preliminary biological assay, focused on antimicrobial activity, carried out using the plant organic extracts, and the isolation and chemical and biological characterization of the secondary metabolites obtained. Thus 3-hydroxy-4-methoxybenzoic acid methyl ester (syn: methyl isovanillate, (1), methyl syringate (2), pinoresinol (3), erythrinassinate C (4) and tyrosol palmitate (5) were isolated. Their antimicrobial activity was tested on several strains and compound 4 showed promising antibacterial activity against Enterococcus faecalis. Thus, this metabolite has antibiotic potential against the drug-resistant opportunistic pathogen E. faecalis.

Abstract Anaemia is a global public health problem affecting 800 million women and children globally. Anaemia is associated with perinatal mortality, child morbidity and mortality, mental development, immune competence, susceptibility to lead poisoning and performance at work. The objective of this article is to identify whether antenatal care‐seeking was associated with the uptake of iron supplementation among pregnant women, adjusting for a range of covariates. This article used data from the cross‐sectional recent Demographic and Health Surveys (DHS) of 12 countries in Asia, Africa and Latin America & the Caribbean regions. The individual‐level data from 273,144 women of reproductive age (15−49 years) were analysed from multi‐country DHS. Multiple Logistic regression analyses were conducted using Predictive Analytics Software for Windows (PASW), Release 18.0. Receiving at least four antenatal care visits was significantly associated with the consumption of 90 or more iron‐containing supplements in 12 low and middle income countries across three regions after adjusting for different household and respondent characteristics, while mass media exposure was found to be a significant predictor in India and Indonesia. Antenatal care seems to be the most important predictor of adherence to iron intake in the selected countries across Africa, Asia, Latin America and Caribbean regions.

Dittrichia viscosa (L.) Greuter, a perennial plant in the Asteraceae, has strong allelopathic activity due to the high content of various secondary metabolites. The bicyclic sesquiterpenoid α‐costic acid is the most abundant secondary metabolite of D. viscosa. Its remarkable insecticidal, antiparasitic, and phytotoxic activities point to its potential use as a natural herbicide, but information on its mode of action is lacking.To shed light on the mechanism of action of α‐costic acid in plant cells, we investigated the phytotoxicity of α‐costic acid in tomato plants (Solanum lycopersicum L.) through in vivo assays, the underlying cellular effects using biochemical assays, and the effect on subcellular organelles using confocal microscopy on tomato protoplasts incubated with organelle‐specific fluorescent probes.In vivo tests showed that α‐costic acid inhibited the growth of tomato seedlings and induced chlorosis and spot lesions in leaves. Biochemical assays demonstrated that α‐costic acid caused ion leakage, chlorophyll depletion, H2O2 overproduction, callose deposition, and membrane lipid peroxidation. Confocal microscopy demonstrated that α‐costic acid determined ROS overproduction and network disruption in mitochondria, singlet oxygen overproduction in chloroplasts, vacuole disintegration, and autophagosome formation.Overall, our data are consistent with a model according to which α‐costic acid phytotoxicity is related to oxidative stress in mitochondria and chloroplasts that induces extensive membrane damage, ultimately resulting in cell death associated with autophagy [ABSTRACT FROM AUTHOR]

The increase in the world population, which will be almost 10 billion by 2050, will require considerable efforts to significantly increase food production. Despite the considerable progress made in agriculture, this need is becoming an emergency due to desertification, environmental pollution and climate changes. Biotic stresses, such as pathogenic bacteria and fungi, primarily contribute to significant losses in agricultural productivity and compromise food safety. These harmful agents are predominantly managed using large quantities of synthetic pesticides. However, this widespread use has led to substantial environmental pollution, increased pest resistance and toxic residues in agricultural produce, which subsequently enter the food supply, posing severe health risks to humans and animals. These challenges have significantly driven the advancement of integrated pest management strategies to reduce or eliminate synthetic pesticides. A practical and viable alternative lies in biopesticides—methods developed from natural products that are safe for human and animal health. This approach aligns with the strong demand from consumers and public authorities for safer pest control solutions. This review was focused on the isolation, chemical and biological characterization of natural products for the biocontrol of phytopathogenic bacteria and, in some cases, fungi with potential eco-friendly applications. [ABSTRACT FROM AUTHOR]

Ascochyta blight, caused by Ascochyta fabae, poses a significant threat to faba bean and other legumes worldwide. Necrotic lesions on stems, leaves, and pods characterize the disease. Given the economic impact of this pathogen and the potential involvement of secondary metabolites in symptom development, a study was conducted to investigate the fungus’s ability to produce bioactive metabolites that might contribute to its pathogenicity. For this investigation, the fungus was cultured in three substrates (Czapek-Dox, PDB, and rice). The produced metabolites were analyzed by NMR and LC-HRMS methods, resulting in the dereplication of seven metabolites, which varied with the cultural substrates. Ascochlorin, ascofuranol, and (R)-mevalonolactone were isolated from the Czapek-Dox extract; ascosalipyrone, benzoic acid, and tyrosol from the PDB extract; and ascosalitoxin and ascosalipyrone from the rice extract. The phytotoxicity of the pure metabolites was assessed at different concentrations on their primary hosts and related legumes. The fungal exudates displayed varying degrees of phytotoxicity, with the Czapek-Dox medium’s exudate exhibiting the highest activity across almost all legumes tested. The species belonging to the genus Vicia spp. were the most susceptible, with faba bean being susceptible to all metabolites, at least at the highest concentration tested, as expected. In particular, ascosalitoxin and benzoic acid were the most phytotoxic in the tested condition and, as a consequence, expected to play an important role on necrosis’s appearance.

Plain language summary Family planning use increased from 17 to 53% in Rwanda in between 2005 and 2015. The purpose of this study is to understand the roles of two types of family planning workers in providing family planning services, how those providers work together to achieve the goal to provide public services, and how the Rwandan health system includes family planning services in a variety of other types of health services. To achieve the study purpose, 32 women with experience using modern methods of contraception were interviewed. In addition, 88 providers participated in eight group discussions to discuss these topics. The results from the interviews and group discussions showed that family planning services are easy to access for Rwandans—due to two types of family planning providers filling different roles to assist Rwandans start and keep using family planning methods. Family planning services are included in services for pregnant, delivering, and postpartum mothers—as well as services for infants and children. These are all times when those adults using the services would also be in need of family planning services. The family planning service delivery team approach—as well as including family planning services in mother’s and children’s health services likely helps explain the increase in family planning use in Rwanda. Other nations might learn from Rwanda’s service delivery approach to family planning to also increase access to family planning for their citizens.

Abstract Background In Rwanda, nearly a third of contraceptive users discontinue within the first year of use. Family planning programs often focus more on recruitment of new users as opposed to maintaining use among current users. A focus on sustaining users and minimizing discontinuation is imperative for long-term family planning program success. This study explores the efforts providers and contraceptive users in Rwanda employ to prevent one of the greatest challenges to family planning programs: contraceptive discontinuation. Methods This was a qualitative study conducted in Rwanda between February and July 2018. It included eight focus group discussions with 88 family planning providers and 32 in-depth interviews with experienced modern contraceptive users. Data were collected in two districts with the highest (Musanze) and lowest (Nyamasheke) rates of contraceptive use. Data were analyzed using thematic content approach. Results Family planning providers in this study used the following strategies to prevent discontinuation: counseling new users on the potential for side effects and switching, reminding clients about appointments for resupply, as well as supporting dissatisfied users by providing counseling, medicine for side effects, and discussing options for switching methods. Users, on the other hand, employed the following strategies to prevent discontinuation: having an understanding that experiences of side effects vary by individuals, supporting peers to sustain use, persisting with use despite experiences of side effects, and switching methods. Conclusions The strategies used by family planning providers and users in Rwanda to prevent discontinuation suggest the possibility of long-term sustained use of contraception in the country. Harnessing and supporting such strategies could contribute to sustaining or improving further contraceptive use in the country.

Abstract Grapevine trunk diseases (GTDs) are well-known and significant fungal diseases of Vitis vinifera with a worldwide distribution. During August to November 2016 in a survey to characterize fungi associated with grapevine trunk diseases in Kermanshah Province (west of Iran) vineyards, 286 fungal isolates were obtained. Based on morphology and DNA sequences data eight species were identified, of which Biscogniauxia rosacearum, Neoscytalidium hyalinum and Phaeoacremonium minimum were the most aggressive fungal pathogenic species characterized in this research. N. hyalinum was the most prevalent species. N. hyalinum and Ph. minimum have previously been reported from Vitis vinifera. Thus far, there are two records of Biscogniauxia mediterranea and Biscogniauxia capnodes on grapevine in the world with no data on pathology aspects. To our knowledge, it is the first time B. rosacearum is reported from grapevine across the globe. Pathogenicity test with three strains of B. rosacearum on 2-year-old potted grapevines confirmed the pathogenicity of B. rosacearum on grapevine. The proximity of vineyards to the oak trees in Zagros forests as one of the plant hosts of Biscogniauxia spp. further highlights the need for extensive studies on B. rosacearum as a new fungal pathogen.

Abstract The epithelial–mesenchymal transition (EMT) imparts properties of cancer stem-like cells, including resistance to frequently used chemotherapies, necessitating the identification of molecules that induce cell death specifically in stem-like cells with EMT properties. Herein, we demonstrate that breast cancer cells enriched for EMT features are more sensitive to cytotoxicity induced by ophiobolin A (OpA), a sesterterpenoid natural product. Using a model of experimentally induced EMT in human mammary epithelial (HMLE) cells, we show that EMT is both necessary and sufficient for OpA sensitivity. Moreover prolonged, sub-cytotoxic exposure to OpA is sufficient to suppress EMT-imparted CSC features including sphere formation and resistance to doxorubicin. In vivo growth of CSC-rich mammary cell tumors, is suppressed by OpA treatment. These data identify a driver of EMT-driven cytotoxicity with significant potential for use either in combination with standard chemotherapy or for tumors enriched for EMT features.

Abstract Background Rwanda has markedly increased the nation’s contraceptive use in a short period of time, tripling contraceptive prevalence in just 5 years between 2005 and 2010. An integral aspect of family planning programs is the interactions between family planning providers and clients. This study aims to understand the client-provider relationship in the Rwandan family planning program and to also examine barriers to those relationships. Methods This qualitative study in Rwanda utilized convenience sampling to include eight focus group discussions with family planning providers, both family planning nurses and community health workers, as well as in-depth interviews with 32 experienced modern contraceptive users. Study participants were drawn from the two districts in Rwanda with the highest and lowest modern contraceptive rates, Musanze and Nyamasheke, respectively Data analysis was guided by the thematic content approach, Atlas.ti 8 was utilized for coding the transcripts and collating the coding results, and Microsoft Excel for analyzing the data within code. Results Data analysis revealed that, despite workplace related challenges – including inadequate staffing, training, and resources, relationships between providers and clients are strong. Family planning providers work hard to understand, learn from, and support clients in their initiation and sustained use of contraceptives. Conclusion Given the existing context of purposeful efforts on the part of family planning providers to build relationships with their clients, if the current level of government support for family planning service provision is enhanced, Rwanda will likely sustain many current users of contraception and engage even more Rwandans in contraceptive services in the future.

Abstract Background Supportive male involvement is strongly correlated with contraceptive use. In Rwanda, where the contraceptive prevalence rate among married women increased from 17 to 52% from 2005 to 2010, and stagnated at 53% in 2015, understanding the role of male partners in collaborative couple contraceptive use can help inform programs designed to further increase the use of contraception in Rwanda. Methods This study utilized qualitative methods in 2018, specifically 32 in-depth interviewers with mostly current users of modern contraceptive methods and eight focus group discussions with family planning providers—both family planning nurses and community health workers (CHWs). Respondents were from Musanze and Nyamasheke Districts, the districts with the highest and lowest modern contraceptive use, respectively, to explore the role of couple collaboration in family planning use in Rwanda. Data were analyzed using the thematic content approach in Atlas.ti (8). Results Findings demonstrate that some men are opposed to use of male methods of contraception, and some are opposed to any contraceptive use, which can lead to covert use. Women and providers prefer collaborative couple contraceptive use—as a result, providers advocate for and encourage male partner participation in contraceptive use. Women are most often burdened with seeking out information, initiating discussions, and sharing information discovered about contraceptive use with partners. Decision-making about contraceptive use, once discussed, can be collaborative and motivated by financial considerations. When couple contraceptive use is collaborative, benefits range from marital harmony to husband’s support of sustained use through reminders about appointments, joint counseling, and support in managing side effects. Conclusion Family planning providers at the community and clinic levels encourage collaborative contraceptive use among couples and some Rwandan couples communicate well about family planning use. Despite the positives, women are expected to source family planning information, share that information with their male partners, seek out family planning services, and use family planning. If more Rwandan male partners accepted use, used male methods of contraception, and participated even more in the work it takes to use family planning, the potential for sustained, and even enhanced, contraceptive use in Rwanda could be realized.

Different fungal species belonging to the Colletotrichum genus cause anthracnose disease in a range of major crops, resulting in huge economic losses worldwide. Typical symptoms include dark, sunken lesions on leaves, stems, or fruits. Colletotrichum spp. have synthesized, in vitro, a number of biologically active and structurally unusual metabolites that are involved in their host’s infection process. In this study, we applied a one strain many compounds (OSMAC) approach, integrated with targeted and non-targeted metabolomics profiling, to shed light on the secondary phytotoxic metabolite panels produced by pathogenic isolates of Colletotrichum truncatum and Colletotrichum trifolii. The phytotoxicity of the fungal crude extracts was also assessed on their primary hosts and related legumes, and the results correlated with the metabolite profile that arose from the different cultural conditions. To the best of our knowledge, this is the first time that the OSMAC strategy integrated with metabolomics approaches has been applied to Colletotrichum species involved in legume diseases.

The alkaloids are one of the most represented family of natural occurring biological active compounds. Amaryllidaceae are also very well known for their beautiful flower and are thus used as ornamental plants in historic and public gardens. The Amaryllidacea alkaloids constitute an important group that is subdivided into different subfamilies with different carbon skeletons. They are well known from ancient times for their long application in folk medicine, and in particular, Narcissus poeticus L. was known to Hippocrates of Cos (ca. B.C. 460–370), who treated uterine tumors with a formulate prepared from narcissus oil. To date, more than 600 alkaloids of 15 chemical groups exhibiting various biological activities have been isolated from the Amaryllidaceae plants. This plant genus is diffused in regions of Southern Africa, Andean South America and the Mediterranean basin. Thus, this review describes the chemical and biological activity of the alkaloids collected in these regions in the last two decades as weel those of isocarbostyls isolated from Amaryllidaceae in the same regions and same period.

In the original article [...]