Organism aging is characterized by increased inflammation and decreased stem cell function, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells (HSPCs) exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signaling, which increases chromatin accessibility in the vicinity of NF-κB target genes in response to inflammation. Rad21 is required for normal differentiation, but limits self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB–dependent manner. HSCs from aged mice fail to down-regulate Rad21/cohesin and inflammation/differentiation signals in the resolution phase of inflammation. Inhibition of cohesin/NF-κB reverts hypersensitivity of aged HSPCs to inflammation-induced differentiation and myeloid-biased HSCs with disrupted/reduced expression of Rad21/cohesin are increasingly selected during aging. Together, Rad21/cohesin-mediated NF-κB signaling limits HSPC function during aging and selects for cohesin-deficient HSCs with myeloid-skewed differentiation.

Malaria presents an overwhelming public health challenge, particularly in sub-Saharan Africa where vector favourable conditions and poverty prevail, potentiating the disease burden. Behavioural variability of malaria vectors poses a great challenge to existing vector control programmes with insecticide resistance already acquired to nearly all available chemical compounds. Thus, approaches incorporating plant-derived compounds to manipulate semiochemical-mediated behaviours through disruption of mosquito olfactory sensory system have considerably gained interests to interrupt malaria transmission cycle. The combination of push-pull methods and larval control have the potential to reduce malaria vector populations, thus minimising the risk of contracting malaria especially in resource-constrained communities where access to synthetic insecticides is a challenge. In this review, we have compiled information regarding the current status of knowledge on manipulation of larval ecology and chemical-mediated behaviour of adult mosquitoes with plant-derived compounds for controlling mosquito populations. Further, an update on the current advancements in technologies to improve longevity and efficiency of these compounds for field applications has been provided.

Premna resinosa (Hochst.) Schauer also called “mukarakara” in Mbeere community of Kenya is used in the management of respiratory illness. In this study we investigated antituberculous, antifungal, antibacterial activities including cytotoxicity and phytochemical constituents of this plant. Antibacterial and antifungal activities were investigated by disc diffusion and micro dilution techniques. Antituberculous activity was investigated using BACTEC MGIT 960 system while cytotoxicity was analyzed by MTT assay on Vero cells (Methanolic crude extract) and HEp-2 cells (fractions). Finally, phytochemicals were profiled using standard procedures. P. resinosa had high antituberculous activity with a MIC of <6.25 μg/ml in ethyl acetate fraction. The antibacterial activity was high and broad spectrum, inhibiting both Gram positive and Gram negative bacteria. Dichloromethane fraction had the best antibacterial MIC of 31.25 μg/ml against Methicillin-resistant S. aureus while Ethyl acetate fraction had the highest zone of inhibition of 22.3 ± 0.3 against S. aureus. Its effects on tested fungi were moderate with petro ether fraction giving an inhibition of 10.3 ± 0.3 on C. albicans. The crude extract and two fractions (petro ether and methanol) were not within the acceptable toxicity limits, however dichloromethane and ethyl acetate fractions that exhibited higher activity were within the acceptable toxicity limit (CC50 < 90). The activity can to some extent be associated to alkaloids, flavonoids, terpenoids, anthraquinones and phenols detected in this plant extracts. Our findings demonstrate that P. resinosa has high selective potential as a source of novel lead for antituberculous, antibacterial and antifungal drugs. Of particular relevance is high activity against MRSA, S. aureus, C. albicans and MTB which are great public health challenge due to drug resistance development and as major sources of community and hospital based infections.

Objectives: We and others have shown that Aspilia pluriseta is associated with various biological activities. However, there is a lack of information on its cytotoxicity. This has created an information gap about the safety of A. pluriseta extracts. As an extension to our recent publication on the antimicrobial activity and the phytochemical characterization of A. pluriseta root extracts, here we report on cytotoxicity of tested solvent fractions. We evaluated the potential cytotoxicity of these root extract fractions on Vero cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: We show that all solvent extract fractions (except methanolic solvent fractions) had cytotoxic concentration values that killed 50% of the Vero cells (CC₅₀) greater than 20 µg/mL and selectivity index (SI) greater than 1.0. Taken together, we demonstrate that, A. pluriseta extract fractions’ earlier reported bioactivities are within the acceptable cytotoxicity and selective index limits. This finding scientifically validates the potential use of A. pluriseta in the discovery of safe therapeutics agents.

Anopheles arabiensis and A. gambiae (sensu stricto) are the most prolific Afrotropical malaria vectors. Population control efforts of these two vectors have been hampered by extremely diverse larval breeding sites and widespread resistance to currently available insecticides. Control of mosquito larval stages using bioactive compounds of plant origin has the potential to suppress vector populations leading to concomitant reduction in disease transmission rates. In this study, we evaluated the efficacy of Camellia sinensis crude leaf extract and its fraction against the larvae of A. arabiensis and A. gambiae (s.s.). Late third/early fourth instar larvae (L3/L4) of A. arabiensis and A. gambiae (s.s.) were exposed to increasing doses of C. sinensis leaf extract and its active fraction for 72 h, with mortality rates recorded every 24 h in both control and test groups. Ultra performance liquid chromatography electron spray ionization quadruple time of flight coupled with mass spectrometry (UPLC/ESI-Qtof/MS) was used to determine the main active constituents in the fraction. The major bioactive chemical constituents in the C. sinensis leaf extract were identified to be proanthocyanidins. The extract significantly interfered with larval survival and adult emergence in both species (ANOVA, F (5,24) = 1435.92, P < 0.001). Additionally, larval exposure to crude extract at 250 ppm and 500 ppm for 24 h resulted in larval mortality rates of over 90 % in A. gambiae (s.s.) and 75 % in A. arabiensis. A relatively lower concentration of 100 ppm resulted in moderate mortality rates of < 50 % in both species, but induced growth disruption effects evident as abnormal larval-pupal intermediates and disrupted adult emergence. The estimated LC50 concentrations of the crude leaf extract against A. arabiensis and A. gambiae (s.s.) larvae at 24 h were 154.58 ppm (95 % CI: 152.37–158.22) and 117.15 ppm (95 % CI: 112.86–127.04), respectively. The bioactive polar fraction caused 100 % larval mortality in both vector species at 25 ppm. Our findings demonstrate the potential of green tea extract and its active constituents in disrupting mosquito larval development. This could contribute to the control of mosquito populations and improved management of malaria.