Efficacy and safety of nanoparticle albumin-bound paclitaxel in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials and observational studies.

Background: The efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in advanced non-small cell lung cancer (NSCLC) have yielded inconsistent findings. Materials and methods: We conducted a systematic review and meta-analysis, including comparative and noncomparative trials and cohort studies, to assess the efficacy and safety of nab-paclitaxel in advanced NSCLC. The search covered PubMed, CENTRAL, Scopus, and ClinicalTrials.gov until October 2022. Efficacy outcomes (OR, PR, progressive disease, OS, and PFS) and safety outcomes (neutropenia, leukopenia, thrombocytopenia, anemia, and sensory neuropathy) were analyzed. Results: Our meta-analysis included data from 35 studies (9 RCTs, 2 cohort studies, and 24 noncomparative studies). Nab-paclitaxel significantly improved OR rate (RRRCT 1.35 [95% CI 1.19, 1.53], I2 = 36.6%; RRcohort 1.67 [95% CI 1.30, 2.14], I2 = 4.3%) and PR rate (RRRCT 1.34 [95% CI 1.18, 1.53], I2 = 38.8%; RRcohort 1.59 [95% CI 1.22, 2.07], I2 = 19.4%) compared to the control group. It further demonstrated more pronounced benefits in squamous cell carcinoma and as a second-line treatment. Pooled evidence from the RCTs also indicated improved OS (HR 0.90 [95% CI 0.81, 0.99], I2 = 9.2%) and PFS (HR 0.84 [95% CI 0.76, 0.93], I2 = 14.5%) However, evidence on the reduction of adverse events with nab-paclitaxel treatment was insufficient, and biases in study selection and detection may have influenced the results. Conclusions: Nab-paclitaxel enhances OR, PR, PFS, and marginally improves OS in advanced NSCLC, particularly in patients with prior chemotherapy. Further research is needed to establish its safety advantages.

Curcumin-loaded albumin submicron particles with potential as a cancer therapy: an in vitro study.

Curcumin (CUR), a polyphenolic compound, shows promising biological properties, particularly antioxidant activity. However, its medical applications are limited due to its low water solubility, bioavailability, and pH-instability. CUR-loaded albumin microparticles (CUR-HSA-MPs) of submicron size in the range of 800 to 900 nm and a zeta potential of -15 mV were prepared. The CUR loading efficiency was up to 65%. A maximum release of 37% of the encapsulated CUR was observed within 6 h when the CUR-HSA-MPs were dispersed in 50% ethanol in PBS at pH 7, while in RPMI 1640 medium the release was 7%. This demonstrates a sustainable release. The in vitro cytotoxicity of CUR-HSA-MPs showed promising anticancer potential against human hepatocellular carcinoma (Huh-7) and human breast adenocarcinoma (MCF-7) cell lines, although this effect was less pronounced in human dermal fibroblasts (HDFB) and human cholangiocyte (MMN) cell lines. Confocal microscopy was used to confirm the uptake of CUR-HSA-MPs by cancer cells. Our studies revealed that HSA-MPs are potentially promising vehicles for increasing the solubility and bioavailability of CUR.

Anti-cancer effect of a phytochemical compound - 7R-acetylmelodorinol - against triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype currently lacking effective treatment options. Consequently, novel and effective drugs or compounds are urgently needed to treat TNBC. Therefore, this study aimed to evaluate the potential of 7R-acetylmelodorinol (7R-AMDL), a phytochemical compound isolated from Xylopia pierrei Hance, a plant found in Thailand, as a novel therapeutic agent for TNBC. MTT and clonogenic assays showed that 7R-AMDL significantly reduced the survival of breast cancer cell lines, with a markedly potent effect on MDA-MB-231 cells. Flow cytometry showed that treating MDA-MB-231 cells with 7R-AMDL at the concentration of dose 8 µM significantly increased early and late apoptosis after 24 and 48 h compared to the control group (p < 0.0001). The highest tested 7R-AMDL dose upregulated the death receptors and their ligands, with extrinsic and intrinsic apoptosis pathways significantly activated via the caspase cascade, compared to the untreated group (p < 0.05). In addition, immunoblots showed decreased BCL2-like 1 (BCL2L1/Bcl-xL) expression (p < 0.0001). Furthermore, wound healing and Transwell assays showed that at a non-cytotoxic dose (≤4 µM), 7R-AMDL significantly inhibited the MDA-MB-231 cell migration and invasion. This reduction in cell migration was associated with decreased matrix metallopeptidase 9 (MMP-9) expression (p < 0.01) and nuclear factor kappa B (NF-κB) activation (p < 0.05). Altogether, 7R-AMDL has anti-cancer effects against TNBC and the potential to be further developed and evaluated for treating this disease.

Evaluation of Anti-Hyperglycemia and Complications of Red and Black Thai Jasmine Rice Cultivars in Streptozotocin-Induced Diabetic Rats.

The phytochemical constituents of red (RR) and black (BR) rice extracts were determined using high-pressure liquid chromatography (HPLC). Phytochemical screening revealed the presence of catechin, rutin, isoquercetin, cyanidin 3-glucoside, cyanidin 3-O-rutinoside, peonidin and quercetin. The anti-diabetic activities of RR and BR extracts on diabetic complications were examined in a streptozotocin-induced diabetic rat model. Rats (n = 80) were divided into 10 groups (n = 8 rats per group). Healthy and diabetic RR or BR-treated groups received 10, 50, or 200 mg of RR or BR per kg of body weight daily for 45 days. The results demonstrated significantly improved glucose control in rats administered RR or BR, while triglyceride and cholesterol levels were reduced in the diabetic groups. Moreover, RR or BR treatment led to decreased levels of malondialdehyde, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine. Further, glutathione concentration was significantly increased in both serum and liver tissue from RR- and BR-treated diabetic rats.

High prevalence of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates: A 5-year retrospective study at a Tertiary Hospital in Northern Thailand.

Background: The global emergence and spread of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, especially Escherichia coli and Klebsiella pneumoniae, have been recognized as a public health concern as severe infections caused by these microorganisms increase morbidity and mortality. This study aimed to assess the prevalence of ESBL-positive E. coli and K. pneumoniae strains isolated from hospitalized patients in Chiangrai Prachanukroh hospital, Chiangrai province, Thailand. Methods: This retrospective analysis was conducted from January 2016 to December 2020. A total of 384,001 clinical specimens were collected aseptically and further cultivated on an appropriate medium. All clinical isolates (one isolate per patient) were identified based on standard laboratory methods. Antibiotic susceptibility testing was performed by the Kirby Bauer disc diffusion technique following CLSI guidelines. ESBL production was screened with ceftazidime and cefotaxime discs based on the CLSI recommendations. Phenotypic confirmation of ESBL production was carried out using a double-disc synergy technique following the CLSI standard. Results: Of a total of 384,001 clinical samples analyzed for bacterial species identification, 11,065 (2.9%) tested positive for E. coli and 5,617 (1.5%) for K. pneumoniae. Approximately 42.5% (4,706/11,065) of E. coli and 30.2% (1,697/5,617) of K. pneumoniae isolates were classified as ESBL producers. A higher proportion of ESBL producers was found in patients older than 60 years and male groups. The highest infection rates of ESBL-positive pathogens were observed among patients in a medical unit. ESBL-producing E. coli and K. pneumoniae isolates were predominantly found in urine and sputum, respectively. ESBL producers exhibited a high resistance rate to ampicillin (99.8-100%), cefazolin (100%), cefotaxime (100%), fluoroquinolones, and trimethoprim/sulfamethoxazole. Conclusions: This study demonstrated the high prevalence and emerging antibiotic resistance of ESBL-positive E. coli and K. pneumoniae isolates from patients admitted to a provincial hospital in northern Thailand. Most ESBL-producing strains were highly resistant to several antimicrobial agents apart from carbapenems and aminoglycosides. These findings indicated that carbapenems and aminoglycosides should be advised as the first-line drugs of choice for serious infections with ESBL-producing Enterobacterales.

Accumulation of lipid peroxidation-derived DNA lesions in iron-overloaded thalassemic mouse livers: comparison with levels in the lymphocytes of thalassemia patients.

In thalassemia patients, iron overload can stimulate lipid peroxidation (LPO), thereby generating miscoding DNA adducts. Adducted DNA was measured in the lymphocytes of beta-Thal/Hb E patients and healthy controls and in the organs of thalassemic mice. epsilondA, epsilondC and M(1)dG residues were quantified by (32)P-postlabeling-TLC/HPLC. M(1)dG levels in lymphocyte DNA from patients were 4 times as high as in controls, while the increase in epsilondA and epsilondC was not significant. Adducted DNA accumulated in the liver of thalassemic mice having >2.7 mg Fe/g tissue dry weight; DNA adducts and iron were highly correlated. epsilondA was not specifically generated in certain mouse liver cell types as revealed by immunohistochemical staining. We found elevated LPO-induced DNA damage in the liver of thalassemic mouse and in lymphocytes, implicating that massive DNA damage occurs in the liver of thalassemia patients. We conclude that promutagenic LPO-derived DNA lesions are involved in the onset of hepatocellular carcinoma in these patients.

Increased urinary 1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine excretion in thalassemia patients: markers for lipid peroxidation-induced DNA damage.

Thalassemic diseases including homozygous beta-thalassemia and beta-thalassemia/Hb E (beta-Thal/Hb E) are prevalent in Southeast Asia. Iron overload is a common complication in beta-thalassemia patients which induces intracellular oxidative stress and lipid peroxidation (LPO). LPO end products generate miscoding etheno adducts in DNA which after their repair are excreted in urine. We investigated whether urinary levels of 1,N6-ethenodeoxyadenosine (epsilondA) and 3,N4-ethenodeoxycytidine (epsilondC) can serve as putative cancer risk markers in beta-Thal/Hb E patients. epsilondA and epsilondC levels were assayed in collected urine samples by immunoprecipitation-HPLC-fluorescence and 32P-postlabeling TLC, respectively. Mean epsilondA (fmol/micromol creatinine) levels in urine of beta-Thal/Hb E patients ranged from 4.8 to 120.4 (33.8+/-3.9; n=37) and were 8.7 times higher compared to asymptomatic controls (1.4-13.8; 3.9+/-0.8; n=20). The respective epsilondC levels ranged from 0.15 to 32.5 (5.2+/-1.3; n=37) and were increased some 13 times over controls (0.04-1.2; 0.4+/-0.7; n=20). epsilondC levels were correlated positively with NTBI (r=0.517; P=0.002), whereas epsilondA showed only a trend (r=0.257; P=0.124). We conclude that the strongly increased urinary excretion of etheno adducts indicates elevated LPO-induced DNA damage in internal organs such as the liver. These highly promutagenic lesions may contribute to the increased risk of thalassemia patients to develop hepatocellular carcinoma.

Iron-chelating and free-radical scavenging activities of microwave-processed green tea in iron overload.

Secondary iron overload is found in beta-thalassemia (thal) patients because of increased dietary iron absorption and multiple blood transfusions. Excessive iron catalyzes free-radical generation, leading to oxidative damage and vital organ dysfunction. Non-transferrin-bound iron (NTBI) detected in thalassemic plasma is highly toxic and chelatable. Though used to treat iron overload, desferrioxamine (DFO) and deferiprone (L1) also have adverse effects. Green tea (GT) shows many pharmacological effects, particularly antioxidative and iron-chelating capacities. This study was performed to investigate the ability of GT extracts to reduce plasma NTBI concentration and oxidative stress in vitro. The Fe(3+) was found to bind to GT crude extract and form a complex. Green tea crude extract time- and dose-dependently decreased plasma NTBI concentration and counteracted the increase of oxidative stress in both Fe(2+)-EDTA-treated human plasma and erythrocytes. Green tea is a bifunctional natural product that could be relevant for management of iron overload and oxidative stress.