Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway

Multiple myeloma (MM) is a hematologic malignancy associated with malignant plasma cell proliferation in the bone marrow. Despite the available treatments, drug resistance and adverse side effects pose significant challenges, underscoring the need for alternative therapeutic strategies. Natural products, like the fungal metabolite neosetophomone B (NSP-B), have emerged as potential therapeutic agents due to their bioactive properties. Our study investigated NSP-B's antitumor effects on MM cell lines (U266 and RPMI8226) and the involved molecular mechanisms. NSP-B demonstrated significant growth inhibition and apoptotic induction, triggered by reduced AKT activation and downregulation of the inhibitors of apoptotic proteins and S-phase kinase protein. This was accompanied by an upregulation of p21Kip1 and p27Cip1 and an elevated Bax/BCL2 ratio, culminating in caspase-dependent apoptosis. Interestingly, NSP-B also enhanced the cytotoxicity of bortezomib (BTZ), an existing MM treatment. Overall, our findings demonstrated that NSP-B induces caspase-dependent apoptosis, increases cell damage, and suppresses MM cell proliferation while improving the cytotoxic impact of BTZ. These findings suggest that NSP-B can be used alone or in combination with other medicines to treat MM, highlighting its importance as a promising phytoconstituent in cancer therapy.     

Application of homobrassinolide enhances growth,yield and quality of tomato

Brassinosteroids (BRs) have emerged as pleiotropic phytohormone owing to their wide function in crop growth and metabolism. Homobrassinolide (HBR) being an analogue of BRs is known to improve the growth, yield and quality parameters in many crop plants. Thus, an evaluation study was conducted for two years (2018 and 2019) to elucidate the performance of tomato plants (Solanum lycopersicum L.) to a novel group of phytohormone,HBR. The field experiment comprised of seven treatments with homobrassinolide 0.04% (Emulsifiable Concentrate) EC at four different concentrations (0.06, 0.08, 0.10 and 0.12 g active ingredient (a.i.) ha^?1) and two well-known growth promoters viz., Gibberellic acid (GA), Naphthalene Acetic Acid (NAA) along with the untreated control. Plant height and chlorophyll concentration were found significantly different in both years of experiment as well as among the different treatments. HBR at 0.12 g a.i. ha^?1 was found better with maximum number of fruits (77.36 plant^?1), fruit length (6.72 cm), fruit breadth (6.45 cm) and fruit weight (80.52 g) over other concentrations and treatments. Fruit yield was more pronounced in the plots treated with plant growth regulators compared to untreated control. However, significantly higher fruit yield of 91.07 t ha^?1 (62.58 t ha^?1 with untreated control) along with improved quality traits viz., fruit firmness (4.11 kg cm^?2), ascorbic acid content (24.09 mg 100 g^?1), total soluble solids (4.43°Brix) and keeping quality (12.50 days) was recorded in 0.12 g a.i. ha^?1 HBR treated plots. Thus, it can be inferred that HBRapplication would be a better option to enhance growth, yield as well as quality traits in tomato.     

<Emphasis Type="Italic">Arbutus andrachne</Emphasis> L. Reverses Sleep Deprivation-Induced Memory Impairments in Rats

Sleep deprivation (SD) is associated with cognitive deficits. It was found to affect the hippocampus region of the brain by impairing memory formation. This impairment is suggested to be caused by elevation in oxidative stress in the body, including the brain during SD. It was hypothesized that the methanolic extract of the fruits of Arbutus andrachne L. (Ericaceae) will prevent chronic SD-induced impairment of hippocampal memory via its antioxidative properties. The methanolic extract of the fruits of A. andrachne was evaluated for its beneficial properties to reverse SD-induced cognitive impairment in rats. Animals were sleep deprived for 8 weeks using a multiple platform model. The extract was administered i.p. at three doses (50, 200, and 500 mg/kg). Behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM). In addition, the hippocampus was dissected to analyze the following oxidative stress markers: glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG, glutathione peroxidase (GPx), and catalase. Chronic SD impaired short- and long-term memories (P < 0.05). Treatment of animals with A. andrachne fruit extract at all doses prevented long-term memory impairment induced by SD while such treatment prevented short-term memory impairment only at 200 and 500 mg/kg dose levels. Moreover, A. andrachne fruit extract normalized the reduction in the hippocampus GSH/GSSG ratio and activity of GPx, and catalase (P < 0.05) induced by chronic sleep deprivation. Chronic sleep deprivation impaired both short- and long-term memory formation, while methanolic extract of A. andrachne fruits reversed this impairment, probably through normalizing oxidative stress in the hippocampus.     

Mixed Liposome Approach for Ratiometric and Sequential Delivery of Paclitaxel and Gemcitabine

Paclitaxel (PTX) and gemcitabine (GEM) are often used in combination due to the synergistic anticancer effects. PTX and GEM combination showed a synergistic effect to SKOV-3 cells at a molar ratio of 1 to 1 and in PTX ? GEM sequence. Liposomes were explored as a carrier of PTX and GEM combination. We optimized the drug loading in liposomes varying the preparation method and co-encapsulated PTX and GEM in a single liposome preparation maintaining the maximum loading efficiency of each drug. However, drug release kinetics from the co-loaded liposomes (LpPG) was suboptimal because of the detrimental effect of PTX on GEM-release control. Instead, a mixture of LpP and LpG, which were separately optimized according to the desired release kinetics, achieved a greater cytotoxic effect than LpPG, due to the attenuation of GEM release relative to PTX. This study illustrates that co-encapsulation in a single carrier is not always desirable for the delivery of drug combinations, when the activity depends on the dosing sequence. These combinations may benefit from the mixed liposome approach, which offers greater flexibility in controlling the ratio and release kinetics of component drugs.     

Lindgomyces angustiascus, (Lindgomycetaceae,Pleosporales, Dothideomycetes), a new lignicolous species from freshwater habitats in the USA

In this paper, we describe and illustrate a new species, Lindgomyces angustiascus, from submerged wood in lotic and lentic habitats from Florida, North Carolina and Wisconsin, USA. The new species is characterized by black, partially immersed, flattened, globose ascomata; fissitunicate, long, slender, obclavate asci; and one-septate, hyaline, fusiform ascospores with bipolar appendages, each covered with a gelatinous cap. Maximum Likelihood and Bayesian analyses of partial 18S nrDNA and 28S nrDNA, as well as the entire nuclear ribosomal internal transcribed spacer (ITS1, 5.8S and ITS2) region support the placement and establishment of this new species in the Lindgomycetaceae, Pleosporales, Dothideomycetes. Chemical analysis of the organic extract of L. angustiascus revealed the presence of 6E,9E-octadecadienoic acid and ergosterol peroxide as major secondary metabolites.     

Piperazine derivatives with potent drug moiety as efficient acetylcholinesterase,butyrylcholinesterase, and glutathione S-transferase inhibitors

Cholinesterases catalyze the breakdown of the neurotransmitter acetylcholine (ACh), a naturally occurring neurotransmitter, into choline and acetic acid, allowing the nervous system to function properly. In the human body, cholinesterases come in two types, including acetylcholinesterase (AChE; E.C.3.1.1.7) and butyrylcholinesterase (BChE; E.C.3.1.1.8). Both cholinergic enzyme inhibitors are essential in the biochemical processes of the human body, notably in the brain. On the other hand, GSTs are found all across nature and are the principal Phase II detoxifying enzymes in eukaryotes and prokaryotes. Specific isozymes are identified as therapeutic targets because they are overexpressed in various malignancies and may have a role in the genesis of other diseases such as neurological disorders, multiple sclerosis, asthma, and especially cancer cell. Piperazine chemicals have a role in many biological processes and have fascinating pharmacological properties. As a result, therapeutically effective piperazine research is becoming more prominent. Half maximal inhibition concentrations (IC₅₀) of piperazine derivatives were found in ranging of 4.59–6.48 µM for AChE, 4.85–8.35 µM for BChE, and 3.94-8.66 µM for GST. Also, piperazine derivatives exhibited Ki values of 8.04 ± 5.73–61.94 ± 54.56, 0.24 ± 0.03–32.14 ± 16.20, and 7.73 ± 1.13–22.97 ± 9.10 µM toward AChE, BChE, and GST, respectively. Consequently, the inhibitory properties of the AChE/BChE and GST enzymes have been compared to Tacrine (for AChE and BChE) and Etacrynic acid (for GST).