Shotgun metagenomics and computational profiling of the plastisphere microbiome: unveiling the potential of enzymatic production and plastic degradation.

Plastic pollution is one of the most resilient types of pollution and is considered a global environmental threat, particularly in the marine environment. This study aimed to identify plastic-degrading bacteria from the plastisphere and their pharmaceutical and therapeutic potential. We collected samples from soil and aquatic plastisphere to identify the bacterial communities using shotgun metagenomic sequencing and bioinformatic tools. Results showed that the microbiome comprised 93% bacteria, 0.29% archaea, and 3.87% unidentified microbes. Of these 93% of bacteria, 54% were Proteobacteria, 23.9% were Firmicutes, 13% were Actinobacteria, and 2.1% were other phyla. We found that the plastisphere microbiome was involved in degrading synthetic and polyhydroxy alkanoate (PHA) plastic, biosurfactant production, and can thrive under high temperatures. However, no association existed between thermophiles, synthetic plastic or PHA degraders, and biosurfactant-producing bacterial species except for Pseudomonas. Other plastisphere inhabiting plastic degrading microbes include Streptomyces, Bacillus, Achromobacter, Azospirillum, Bacillus, Brevundimonas, Clostridium, Paenibacillus, Rhodococcus, Serratia, Staphylococcus, Thermobifida, and Thermomonospora. However, the plastisphere microbiome showed potential for producing secondary metabolites that were found to act as anticancer, antitumor, anti-inflammatory, antimicrobial, and enzyme stabilizers. These results revealed that the plastisphere microbiome upholds clinical and environmental significance as it can open future portals in a multi-directional way.

Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, especially in Asian countries. The emergence of its drug resistance and its side effects demands alternatives, to improve prognosis. Since the majority of cancer drugs are derived from natural sources, it provides a window to look for more biocompatible alternatives. In this study, two natural compounds, costunolide (CE) and aloe emodin (AE), were isolated from the stem of Lycium shawii. The compounds were examined for their anticancer and apoptotic potentials against OSCC (CAL 27) cells, using an in vitro analysis, such as a MTT assay, scratch assay, gene, and protein expressions. Both compounds, CE and AE, were found to be cytotoxic against the cancer cells with an IC50 value of 32 and 38 µM, respectively. Moreover, the compounds were found to be non-toxic against normal NIH-3T3 cells and comparable with the standard drug i.e., 5-fluorouracil (IC50 = 97.76 µM). These compounds were active against normal cells at higher concentrations. Nuclear staining displayed the presence of apoptosis-associated morphological changes, i.e., karyopyknosis and karyorrhexis in the treated cancer cells. Flow cytometry results further confirmed that these compounds induce apoptosis rather than necrosis, as the majority of the cells were found in the late apoptotic phase. Gene and protein expression analyses showed an increased expression of apoptotic genes, i.e., BAK, caspase 3, 6, and 9. Moreover, the compounds significantly downregulated the expression of the anti-apoptotic (BCL-2 L1), metastatic (MMP-2), and pro-inflammatory (COX-2) genes. Both compounds have shown promising anticancer, apoptotic, and anti-migratory activities against the OSCC cell line (i.e., CAL-27). However, further in vivo studies are required to explore these compounds as anticancer agents.

Evaluation of the combination therapy of hydroxyurea and thalidomide in ß-thalassemia.

Transfusion-related complications and lack of resources in low-to-middle-income countries have led to a search for novel therapies to reduce the need for blood transfusions in patients with ß-thalassemia. Hydroxyurea (HU) has demonstrated promising outcomes; additionally, thalidomide has also shown improvement in hemoglobin (Hb) levels for patients with ß-thalassemia in some studies. This study presents the findings of a single-arm nonrandomized trial to evaluate the efficacy of combination therapy of HU and thalidomide in children with ß-thalassemia. A total of 135 patients (median age, 6 [interquartile range, 3-10] years), 77 (57%) males and 58 (43%) females, were followed first using HU alone, for 6 months, and then using the combination of HU and thalidomide for another 6 months. The primary outcome was a response to therapy, as measured by the number of transfusions required and Hb levels, for patients while receiving HU alone and then while using the combination therapy. Study findings showed a significant decline in blood transfusion volume (P < .001) and a significant increase in median Hb levels within 3 and 6 months of the combination therapy (P < .001). Eighty-nine (65.93%) participants were good responders, 16 (11.85%) were responders, and 30 (22.22%) were nonresponders, whereas the responders had variable genetic mutations. A total of 38 adverse events were reported that resolved on supportive treatment or temporary hold of the intervention. The combination therapy demonstrated promising results and could be considered for a diverse patient population with ß-thalassemia. This trial was registered at www.clinicaltrials.gov as #NCT05132270.

Phytochemicals from Carissa carandas with potent cytotoxic and anti-inflammatory activities.

Six natural products (1-6) were isolated from the fresh leaves of Carissa carandas including ursolic acid (1), ursolic acid-γ-lactone (2), 27-O-Z-p-coumaroyl ursolic acid (3), 23-hydroxy ursolic acid (4), uvaol (5) and ursolic aldehyde (6). Their structure elucidation was done by modern spectroscopic techniques including 1H-NMR, 13C-NMR and comparison with reported data. All compounds were known, while 2-4 were isolated for the first time from the genus Carissa. Isolated compounds were screened for their cytotoxic via MTT assay and anti-inflammatory potential via luminol-enhanced chem-iluminescence assay. Compounds 3 and 4 showed potent activity against lung cancer cell line (NCI-H460), and 4 showed potent anti-inflammatory activity against reactive oxygen species production from human whole blood phagocytes. Compound 5 displayed good selective cytotoxicity against NCI-H460 and did not provoke cytotoxicity against normal cell line upto 250 µM. Compounds 3-5 were identified as potential anti-cancer drug leads.

Novel ursane-type triterpene from the fresh leaves of Carissa carandas and evaluation of cytotoxicity.

One novel ursolic acid derivative sabiracin 1 (11,25-epoxy-3ß-hydroxy-urs-12-en-28-oic acid) was isolated from the leaves of Carissa carandas, together with five known compounds para hydroxy benzaldehyde (2), ursolic acid (3), carissin (4), 22α-hydroxyursolic acid (5) and ß-sitosterol-3-O-ß-D-glucopyranoside (6). Compounds 2 and 5 were isolated for the first time from this genus. Structure elucidation was done by the help of spectroscopic techniques. Compounds 1-3, 5 and 6 were examined against oral cancer (CAL-27) and lung cancer (NCI-H460) cell lines. 6 showed good activity against oral cancer (IC50 18.69 µM), moderate activity against lung cancer (IC50 63.34 µM) and no cytotoxicity against normal cell lines.