G2A as a key modulator of carbonyl stress and apoptosis resistance in glucose-loaded cancer cells.

Cancer cells exhibit high glycolytic activity, metabolizing glucose as their primary energy substrate. Toxic metabolites produced during glycolysis, such as methylglyoxal, induce carbonyl stress (CS), promoting inflammation and oxidative stress. The elevated glucose metabolism in cancer cells creates this toxic environment. However, little research has focused on the molecules mediating these reactions and stresses, and their role in selecting and enriching apoptosis-resistant cells. This study investigated the impact of constitutively suppressing oxidized lipid receptor G2A (GPR132) expression on the relationship between CS and oxidative stress in glucose-loaded cancer cells. G2A has recently attracted attention as a tumor promoter. However, our study shows that G2A suppression under glucose loading significantly reduces CS and associated oxidative stress, thereby enhancing cancer cell survival. This suggests a new mechanism contrary to conventional thinking, involving the acute induction of glyoxalase 1 (Glo1). G2A may thus play a role in selecting and enriching apoptosis-resistant cell populations under high glucose conditions by regulating Glo1 expression. These findings improve our understanding of the adaptive capacity of cancer cells to glucose toxicity.

Amino acid deprivation in cancer cells with compensatory autophagy induction increases sensitivity to autophagy inhibitors.

Inhibition of autophagy is an important strategy in cancer therapy. However, prolonged inhibition of certain autophagies in established cancer cells may increase therapeutic resistance, though the underlying mechanisms of its induction and enhancement remain unclear. This study sought to elucidate the mechanisms of therapeutic resistance through repeated autophagy inhibition and amino acid deprivation (AD) in an in vitro model of in vivo chronic nutrient deprivation associated with cancer cell treatment. In the human cervical cancer cell line HeLa and human breast cancer cell line MCF-7, initial extracellular AD induced the immediate expression of endosomal microautophagy (eMI). However, repeated inhibition of eMI with U18666A and extracellular AD induced macroautophagy (MA) to compensate for reduced eMI, simultaneously decreasing cytotoxicity. Here, hyperphosphorylated JNK was transformed into a hypophosphorylated state, suggesting conversion of the cell death signal to a survival signal. In a nutrient medium, cell death could not be induced by MA inhibition. However, since LAT1 inhibitors induce intracellular AD, combining them with MA and eMI inhibitors successfully promoted cell death in resistant cells. Our study identified a novel therapeuic approach for promoting cell death and addressing therapeutic resistance in cancers under autophagy-inhibitor treatment.

Insights into the Biological Activities and Substituent Effects of Pyrrole Derivatives: The Chemistry-Biology Connection.

Pyrrole, with its versatile heterocyclic ring structure, serves as a valuable template for generating a diverse range of lead compounds with various pharmacophores. Researchers and scientists globally are intrigued by pyrrole and its analogs for their broad pharmacological potential, prompting thorough investigations aimed at advancing human welfare. This comprehensive review delves into the diverse activities exhibited by pyrrole compounds, encompassing their synthesis, reactions, and pharmacological properties alongside their derivatives. In addition to detailing the characteristics of pyrrole and its derivatives within the context of green chemistry, the review also examines microwave-assisted reactions. It provides insights into their chemical structures, natural occurrences, and potential applications across various domains. Furthermore, the article investigates structural alterations of pyrrole compounds and their implications on their functionality, highlighting their versatility as foundational elements for both functional materials and bioactive compounds. The review emphasizes the need for ongoing research and development in the field of pyrrole compounds to discover new activities and benefits.

Exploration of Site-Specific Drug Targeting-A Review on EPR-, Stimuli-, Chemical-, and Receptor-Based Approaches as Potential Drug Targeting Methods in Cancer Treatment.

Cancer has been one of the most dominant causes of mortality globally over the last few decades. In cancer treatment, the selective targeting of tumor cells is indispensable, making it a better replacement for conventional chemotherapies by diminishing their adverse side effects. While designing a drug to be delivered selectively in the target organ, the drug development scientists should focus on various factors such as the type of cancer they are dealing with according to which drug, targeting moieties, and pharmaceutical carriers should be targeted. All published articles have been collected regarding cancer and drug-targeting approaches from well reputed databases including MEDLINE, Embase, Cochrane Library, CENTRAL and ClinicalTrials.gov, Science Direct, PubMed, Scopus, Wiley, and Springer. The articles published between January 2010 and December 2020 were considered. Due to the existence of various mechanisms, it is challenging to choose which one is appropriate for a specific case. Moreover, a combination of more than one approach is often utilized to achieve optimal drug effects. In this review, we have summarized and highlighted central mechanisms of how the targeted drug delivery system works in the specific diseased microenvironment, along with the strategies to make an approach more effective. We have also included some pictorial illustrations to have a precise idea about different types of drug targeting. The core contribution of this work includes providing a cancer drug development scientist with a broad preliminary idea to choose the appropriate approach among the various targeted drug delivery mechanisms. Also, the study will contribute to improving anticancer treatment approaches by providing a pathway for lesser side effects observed in conventional chemotherapeutic techniques.

Streblus asper attenuates alloxan-induced diabetes in rats and demonstrates antioxidant and cytotoxic effects.

CONTEXT: Streblus asper Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation. OBJECTIVE: The study evaluates antidiabetic effects, antioxidant potential, and cytotoxicity of leaf and bark extracts of S. asper. MATERIALS AND METHODS: Antidiabetic effects were assessed by inducing diabetes in Wistar albino rats (n = 5, six groups included 30 rats) by injecting alloxan [0.25 mg/kg body weight (bw)] intraperitoneally, and efficacy of methanol extracts of leaf and bark, and aqueous extract of leaves were evaluated by oral administration of 300 mg/kg bw of extracts for 3 weeks. Glibenclamide (Dibenol™) was used as a control (10 mg/kg bw). Antioxidant properties were examined by DPPH free radical scavenging activity, and cytotoxicity was investigated using a brine shrimp lethality assay. RESULTS: Methanol extracts of leaves and bark, and the aqueous extract of leaves of S. asper, caused significant reductions in blood glucose levels in diabetic rats of 36.83, 70.33, and 52.71%, respectively, after 21 days of treatment. IC50 values in DPPH radical scavenging assessment for those extracts were 58.92, 88.54, and 111.36 µg/mL, respectively. LC50 values for brine shrimp lethality for the extracts were 173.80, 32.36, and 3235.9 µg/mL, respectively. DISCUSSION AND CONCLUSIONS: The methanol bark extract of S. asper showed significant antidiabetic activity. This study will significantly contribute to establishing the plant as an alternative medicinal resource for rural populations of Bangladesh and provides an opportunity for further research to identify the primary active compound(s) and establish new drug candidates.

Environmental parameters and stocking density influence growth, feed utilization and economics of butter catfish, Ompok bimaculatus (Bloch, 1794) production in floating net cages in a large tropical reservoir, India.

An experiment was conducted to study the influence of environmental parameters and stocking density on growth, survival, feed utilization, and economic feasibility of a high value butter catfish, Ompok bimaculatus in floating cages in a large tropical reservoir of India for 180 days. The fingerlings (11.44 ± 1.33 cm; 8.05 ± 3.27 g) were stocked at three stocking densities, viz., 15, 25 and 35 fingerlings m-3 in GI cages (32m3) in triplicates. Commercial floating pellets were fed to fish at 5-3% of fish biomass. The results indicated that the fishes at the lowest stocking density of 15 fingerlings m-3 had significantly higher (p < 0.05) growth in relation to weight gain percentage (717.67 ± 39.10) and specific growth rate (1.14 ± 0.05). Survival percentage was also significantly higher (p < 0.01) at lower stocking densities compared with 35 fingerlings m-3. Similarly, the feed conversion efficiency (0.423 ± 0.025), protein efficiency ratio (1.37 ± 0.15) and feed conversion ratio (FCR) (2.37 ± 0.16) were significantly better at density of 15 fingerlings m-3. The fish growth and feed utilization efficiency did not vary significantly (p > 0.05) between stocking densities of 15 fingerlings m-3 and 25 fingerlings m-3. The condition factor was insignificantly higher at lower densities and its values close to 1 indicated congeniality of reservoir ecosystem for cage culture of the species. The coefficient of variation of weight was significantly higher (24.19 ± 1.20) at 35 fingerlings m-3. The highest economic gains in terms of benefit cost ratio (1.77) were achieved at the lowest stocking density. The present study indicated better growth and economic returns at lower stocking densities of 15-25 fingerlings m-3. The nutrient load and plankton abundance were higher at culture site, however, did not vary significantly from reference sites throughout the culture period. Although most of the environmental parameters showed significant seasonal variations, dissolved oxygen showed significant positive relation (r = 0.86) with the growth of the fish. This is the first study reporting feasibility of cage culture of this highly renumerative species in open waters. The cage culture of this species will not only ensure better economic returns to the marginal cage farmers but will aid in the conservation of this species in natural ecosystem. Being a low volume high value species, the impact on environment will be less compared with high volume low value species. This study will serve as baseline for standardization of its grow-out protocol in cages and will be a step towards much needed species diversification for sustainable small scale cage farming in tropical reservoirs of Asia.

Ethnobotanical, phytochemical and toxicological studies of Xanthium strumarium L.

The present study describes the ethnobotanical, phytochemical, and toxicological evaluations of Xanthium strumarium L. growing in Bangladesh. In toxicity evaluation on rats, the methanol extract of seedlings showed mortality, while both seedling and mature plant extracts raised the serum alanine transaminase and aspartate transaminase values and produced significant abnormalities in the histopathology of liver and kidney of rats. On the other hand, the aqueous soluble fraction of methanol extract of mature plant (LC50 = 0.352 microg/mL) and methanol crude extract of seedlings (LC50 = 0.656 microg/mL) demonstrated significant toxicity in the brine shrimp lethality bioassay. A total of four compounds were purified and characterized as stigmasterol (1), 11-hydroxy-11-carboxy-4-oxo-1(5),2(Z)-xanthadien-12,8-olide (2), daucosterol (3) and lasidiol-10-anisate (4). The present study suggests that X. strumarium is toxic to animal.