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1.
Pathol Res Pract ; 258: 155303, 2024 Apr 27.
Article En | MEDLINE | ID: mdl-38728793

Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.

2.
Curr Pharm Des ; 2024 May 09.
Article En | MEDLINE | ID: mdl-38726783

In recent years, the field of nanotechnology has brought about significant advancements that have transformed the landscape of disease diagnosis, prevention, and treatment, particularly in the realm of medical science. Among the various approaches to nanoparticle synthesis, the green synthesis method has garnered increasing attention. Silver nanoparticles (AgNPs) have emerged as particularly noteworthy nanomaterials within the spectrum of metallic nanoparticles employed for biomedical applications. AgNPs possess several key attributes that make them highly valuable in the biomedical field. They are biocompatible, cost-effective, and environmentally friendly, rendering them suitable for various bioengineering and biomedical applications. Notably, AgNPs have found a prominent role in the domain of cancer diagnosis. Research investigations have provided evidence of AgNPs' anticancer activity, which involves mechanisms such as DNA damage, cell cycle arrest, induction of apoptosis, and the regulation of specific cytokine genes. The synthesis of AgNPs primarily involves the reduction of silver ions by reducing agents. Interestingly, natural products and living organisms have proven to be effective sources for the generation of precursor materials used in AgNP synthesis. This comprehensive review aims to summarize the key aspects of AgNPs, including their characterization, properties, and recent advancements in the field of biogenic AgNP synthesis. Furthermore, the review highlights the potential applications of these nanoparticles in combating cancer.

3.
Adv Mater ; : e2402925, 2024 May 08.
Article En | MEDLINE | ID: mdl-38717326

In heterostructures made from polar materials, e.g., AlN-GaN-AlN, the non-equivalence of the two interfaces has long been recognized as a critical aspect of their electronic properties, in that they host different two-dimensional carrier gases. Interfaces play an important role in the vibrational properties of materials, where interface states enhance thermal conductivity and can generate unique infrared-optical activity. The non-equivalence of the corresponding interface atomic vibrations, however, has not been investigated so far due to a lack of experimental techniques with both high spatial and high spectral resolution. Herein we experimentally demonstrate the non-equivalence of AlN-(Al0.65Ga0.35)N and (Al0.65Ga0.35)N-AlN interface vibrations using monochromated electron energy-loss spectroscopy in the scanning transmission electron microscope (STEM-EELS) and employ density-functional-theory (DFT) calculations to gain insights in the physical origins of observations. We demonstrate that STEM-EELS possesses sensitivity to the displacement vector of the vibrational modes as well as the frequency, which is as critical to understanding vibrations as polarization in optical spectroscopies. The combination enables direct mapping of the non-equivalent interface phonons between materials with different phonon polarizations. The results demonstrate the capacity to carefully assess the vibrational properties of complex heterostructures where interface states dominate the functional properties. This article is protected by copyright. All rights reserved.

4.
Med Oncol ; 41(6): 134, 2024 May 04.
Article En | MEDLINE | ID: mdl-38703282

Primary liver cancer is a type of cancer that develops in the liver. Hepatocellular carcinoma is a primary liver cancer that usually affects adults. Liver cancer is a fatal global condition that affects millions of people worldwide. Despite advances in technology, the mortality rate remains alarming. There is growing interest in researching alternative medicines to prevent or reduce the effects of liver cancer. Recent studies have shown growing interest in herbal products, nutraceuticals, and Chinese medicines as potential treatments for liver cancer. These substances contain unique bioactive compounds with anticancer properties. The causes of liver cancer and potential treatments are discussed in this review. This study reviews natural compounds, such as curcumin, resveratrol, green tea catechins, grape seed extracts, vitamin D, and selenium. Preclinical and clinical studies have shown that these medications reduce the risk of liver cancer through their antiviral, anti-inflammatory, antioxidant, anti-angiogenic, and antimetastatic properties. This article discusses the therapeutic properties of natural products, nutraceuticals, and Chinese compounds for the prevention and treatment of liver cancer.


Liver Neoplasms , Signal Transduction , Humans , Liver Neoplasms/prevention & control , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Signal Transduction/drug effects , Carcinoma, Hepatocellular/prevention & control , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Animals , Dietary Supplements , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Phytochemicals/pharmacology , Phytochemicals/therapeutic use
5.
Cureus ; 16(4): e57708, 2024 Apr.
Article En | MEDLINE | ID: mdl-38711698

Introduction Despite the implementation of countermeasures and mass vaccination programs, the COVID-19 pandemic incidence was a vital public health concern. This study aimed to explore the dynamics of COVID-19 cases and assess the association of COVID-19 pandemic epidemiological data with meteorological factors in Hiroshima Prefecture compared to Japan. Methods We analyzed COVID-19 pandemic data in Japan's Hiroshima Prefecture from January 16, 2020, to May 9, 2023. Meteorological factors were examined at different time frames, and Spearman correlation coefficients were calculated for COVID-19 variables and variants based on GISAID whole genome analysis. Results Hiroshima Prefecture reported 816,788 COVID-19 cases and 1,371 fatalities, with a city-to-rural case ratio of 0.97:1. Infection rates were 17.42% for Japan and 15.83% for Hiroshima. Gender-wise, the ratio was 99:1, and the 30-39 age group in Hiroshima had the highest cases (15.5%). Among all meteorological factors, daily and 14-day average wind speed showed a weak correlation with incidence (-0.1954, P < 0.01; 0.3669 P < 0.01), fatalities (-0.1148, P < 0.01; -0.2232 P < 0.01), and incidence rate (-0.2042, P < 0.01; -0.3751, P < 0.01), respectively. Clade GRA was most frequent (39.7%), and among 61 variants, B.1.1.7, AY.29, and BA.1.1.2 were predominant. Precipitation was associated significantly with the Alpha variant (0.3373, P<0.01), while the Delta variant (0.2934, <0.05) weakly correlated with humidity. Conclusion COVID-19 pandemic trends in Hiroshima Prefecture paralleled Japan's, yet with lower incidence and fatalities compared to most prefectures. Significant associations were found between meteorological factors and COVID-19 metrics, including incidence, fatalities, incidence rate, and mutations in Hiroshima.

6.
Health Sci Rep ; 7(4): e2063, 2024 Apr.
Article En | MEDLINE | ID: mdl-38660004

Background and Aims: Non-communicable diseases such as hypertension and diabetes are matters of huge concern worldwide, with an increasing trend in prevalence over the previous decade. First of all, this study aimed to evaluate the association between economic status (ES) and body mass index (BMI), ES and comorbidity of hypertension and diabetes, and BMI and comorbidity independently. Second, it explored the mediating role of BMI in the association between ES and comorbidity of hypertension and diabetes. Finally, it investigated whether the mediating effect differs with the place of residence, gender, and education levels. Methods: A total of 11,291 complete cases from the Bangladesh demographic and health survey 2017-18 were utilized for this study. Survey-based binary logistic regression or multiple logistic regression was used to find the association among outcome, exposure, and mediator variables, and a counterfactual framework-based weighting approach was utilized for mediation analysis. Results: Middle-income (adjusted odds ratio [AOR]: 1.696, 95% confidence interval [CI]: 1.219, 2.360) and rich (AOR: 2.770, CI: 2.054, 3.736) respondents were more likely to have comorbidity of hypertension and diabetes compared to the poor. The odds of comorbidity increased with the increase in BMI. A positive association was observed between ES and BMI. A significant mediating role of BMI in the association between ES and comorbidity was found. We observed that 19.85% (95% CI: 11.50%, 49.6%) and 20.35% (95% CI: 14.9%, 29.3%) of total effect was mediated by BMI for middle and rich respondents, respectively, compared to the poor. Conclusions: The mediating role of BMI was greater for female, no or primary educated respondents, and respondents from rural areas. Therefore, the study will facilitate policymakers of Bangladesh and other countries with a similar set-up to decide on health policies regarding hypertension and diabetes.

7.
Heliyon ; 10(8): e29255, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38681569

The ternary photocatalyst ((Al2Si2O5 (OH)4/TiO2/Al2O3) composites (where w/w = 65, 30, and 5 wt%) denoted K65T30A5 were successfully synthesized and examined for their efficiency in removing cationic (Methylene Blue, MB) and anionic (Remazol Red, RR) dye from aqueous medium under visible-light irradiation. A series of nanocomposites with varied wt% of kaolinite, TiO2, and Al2O3 were prepared through sonication followed by calcination at 600 °C. X-ray diffraction (XRD) analysis confirmed the crystallinity of the synthesized materials and established their average crystal size to be 83.87 nm. The morphological structure, composite molecule, and surface properties of the resulting K65T30A5 were characterized using FTIR, FE-SEM, and EDS analyses to confirm the successful fabrication of the nanocomposite. FTIR and EDS elemental mapping analyses confirmed the presence of Al, Si, Ti, and O elements in the nanocomposites. The composites exhibited photocatalytic behaviour across the UV-visible spectra, with values varying from the ultraviolet to the visible region with a sharp increase in reflectance at 510 nm. Near-complete degradation of MB (97.66 %) was achieved within 90 min at pH 9 and a 10 mg/L dye concentration, while RR removal reached 90.66 % within 120 min at pH 3.5 and the same dye concentration under visible light irradiation. The catalyst exhibited robust stability, retaining its efficiency by removing 85.09 % of MB and 80.21 % of RR dye after three reuse cycles. The composite catalyst discussed in this study emerges as a promising material for straightforward fabrication techniques, featuring a high percentage of kaolinite and proving to be a cost-effective solution for large-scale water and wastewater treatment processes.

8.
BMJ Paediatr Open ; 8(1)2024 Mar 18.
Article En | MEDLINE | ID: mdl-38499349

OBJECTIVES: This study aimed to explore the effects of short birth spacing (SBS), which is defined as a period of less than 33 months between two successive births, on multiple concurrent forms of child malnutrition (MCFCM) and at least one form of child malnutrition (ALOFCM) using propensity score matching (PSM). METHODS: This study used data extracted from the 2017-18 Bangladesh Demographic and Health Survey. PSM with four different distance functions, including logistic regression, classification and regression tree, single hidden layer neural network and random forest, were performed to evaluate the effects of SBS on MCFCM and ALOFCM. We also explored how the effects were modified in different subsamples, including women's empowerment, education and economic status (women's 3E index)-constructed based on women's decision-making autonomy, education level, and wealth index, and age at marriage, and place of residence. RESULTS: The prevalence of SBS was 22.16% among the 4652 complete cases. The matched samples of size 2062 generated by PSM showed higher odds of MCFCM (adjusted OR (AOR)=1.25, 95% CI=1.02 to 1.56, p=0.038) and ALOFCM (AOR=1.20, 95% CI=1.01 to 1.42, p=0.045) for the SBS children compared with their counterparts. In the subsample of women with 3E index≥50% coverage, the SBS children showed higher odds of MCFCM (AOR: 1.43, 95% CI=1.03 to 2.00, p=0.041] and ALOFCM (AOR: 1.33, 95% CI=1.02 to 1.74, p=0.036). Higher odds of MCFCM (AOR=1.27, 95% CI=1.02 to 1.58, p=0.036) and ALOFCM (AOR=1.23, 95% CI=1.02 to 1.51, p=0.032) for SBS children than normal children were also evident for the subsample of mothers married at age≤18 years. CONCLUSION: SBS was significantly associated with child malnutrition, and the effect was modified by factors such as women's autonomy and age at marriage.


Birth Intervals , Child Nutrition Disorders , Child , Humans , Female , Adolescent , Bangladesh/epidemiology , Child Nutrition Disorders/epidemiology , Propensity Score , Mothers
9.
Exp Gerontol ; 188: 112389, 2024 Apr.
Article En | MEDLINE | ID: mdl-38432575

Aging-related diseases (ARDs) are a major global health concern, and the development of effective therapies is urgently needed. Kaempferol, a flavonoid found in several plants, has emerged as a promising candidate for ameliorating ARDs. This comprehensive review examines Kaempferol's chemical properties, safety profile, and pharmacokinetics, and highlights its potential therapeutic utility against ARDs. Kaempferol's therapeutic potential is underpinned by its distinctive chemical structure, which confers antioxidative and anti-inflammatory properties. Kaempferol counteracts reactive oxygen species (ROS) and modulates crucial cellular pathways, thereby combating oxidative stress and inflammation, hallmarks of ARDs. Kaempferol's low toxicity and wide safety margins, as demonstrated by preclinical and clinical studies, further substantiate its therapeutic potential. Compelling evidence supports Kaempferol's substantial potential in addressing ARDs through several mechanisms, notably anti-inflammatory, antioxidant, and anti-apoptotic actions. Kaempferol exhibits a versatile neuroprotective effect by modulating various proinflammatory signaling pathways, including NF-kB, p38MAPK, AKT, and the ß-catenin cascade. Additionally, it hinders the formation and aggregation of beta-amyloid protein and regulates brain-derived neurotrophic factors. In terms of its anticancer potential, kaempferol acts through diverse pathways, inducing apoptosis, arresting the cell cycle at the G2/M phase, suppressing epithelial-mesenchymal transition (EMT)-related markers, and affecting the phosphoinositide 3-kinase/protein kinase B signaling pathways. Subsequent studies should focus on refining dosage regimens, exploring innovative delivery systems, and conducting comprehensive clinical trials to translate these findings into effective therapeutic applications.


Kaempferols , Respiratory Distress Syndrome , Humans , Kaempferols/pharmacology , Kaempferols/therapeutic use , Kaempferols/chemistry , Phosphatidylinositol 3-Kinases , Antioxidants/pharmacology , Antioxidants/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Aging , Respiratory Distress Syndrome/drug therapy
10.
BMC Oral Health ; 24(1): 400, 2024 Mar 29.
Article En | MEDLINE | ID: mdl-38553672

BACKGROUND: Endodontic literature search revealed that no study has been conducted to evaluate the prevalence of apical periodontitis (AP) in root canal treated teeth from an adult Nepalese population of Madhesh Province. Consequently, little is known about the extent and risk factors associated with it. This study aimed to determine AP prevalence in root canal treated teeth from an adult Nepalese subpopulation and to analyze the related risk factors including age, sex, tooth type, type of coronal restoration and quality of root canal treatment and coronal restoration as predictors of AP. METHODS: Digital panoramic radiographs were evaluated. Periapical status of 300 root canal-treated teeth was scored by using the periapical index. The quality of root canal treatment and coronal restorations were categorized as adequate or inadequate through radiographic and clinical evaluation. The data were analyzed using univariate and multivariate logistic regression models. RESULTS: Prevalence of AP in the present study was 31.7%. In 45.7% of the treated teeth, quality of root canal treatment was adequate whereas 46% of the cases had adequate coronal restorations. Multivariate logistic regression analysis revealed statistically significant associations and remarkably increased risk for AP in teeth with inadequate root canal treatment (odds ratio [OR] = 7.92; 95% CI: 3.96-15.82; p < 0.001) whereas lower risk for AP was found in females (OR = 0.51; 95% CI: 0.28-0.90; p = 0.021) and in teeth restored with crown (OR = 0.22; 95% CI: 0.09-0.51; p < 0.001) and filling (OR = 0.18; 95% CI: 0.08-0.42; p < 0.001). Quality of coronal restoration, tooth type and age of the patient were not found to be the predictors of AP. CONCLUSIONS: Within the limits of this study, a high prevalence of AP and poor overall quality of root canal treatment and coronal restoration was found in the subpopulation studied. Quality of root canal treatment, type of coronal restoration and sex of the patient are significant predictors of possible AP development in root canal treated teeth. Substantial efforts are needed to improve the endodontic treatment standards.


Periapical Periodontitis , Tooth, Nonvital , Adult , Female , Humans , Cross-Sectional Studies , Dental Pulp Cavity , Nepal/epidemiology , Dental Restoration, Permanent/adverse effects , Root Canal Therapy/adverse effects , Periapical Periodontitis/epidemiology , Prevalence , Root Canal Obturation , Tooth, Nonvital/epidemiology
11.
Pathol Res Pract ; 256: 155259, 2024 Apr.
Article En | MEDLINE | ID: mdl-38503004

Circular RNAs (circRNAs) have been recognized as key components in the intricate regulatory network of the KRAS pathway across various cancers. The KRAS pathway, a central signalling cascade crucial in tumorigenesis, has gained substantial emphasis as a possible therapeutic target. CircRNAs, a subgroup of non-coding RNAs known for their closed circular arrangement, play diverse roles in gene regulation, contributing to the intricate landscape of cancer biology. This review consolidates existing knowledge on circRNAs within the framework of the KRAS pathway, emphasizing their multifaceted functions in cancer progression. Notable circRNAs, such as Circ_GLG1 and circITGA7, have been identified as pivotal regulators in colorectal cancer (CRC), influencing KRAS expression and the Ras signaling pathway. Aside from their significance in gene regulation, circRNAs contribute to immune evasion, apoptosis, and drug tolerance within KRAS-driven cancers, adding complexity to the intricate interplay. While our comprehension of circRNAs in the KRAS pathway is evolving, challenges such as the diverse landscape of KRAS mutant tumors and the necessity for synergistic combination therapies persist. Integrating cutting-edge technologies, including deep learning-based prediction methods, holds the potential for unveiling disease-associated circRNAs and identifying novel therapeutic targets. Sustained research efforts are crucial to comprehensively unravel the molecular mechanisms governing the intricate interplay between circRNAs and the KRAS pathway, offering insights that could potentially revolutionize cancer diagnostics and treatment strategies.


Neoplasms , RNA, Circular , Humans , RNA, Circular/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Neoplasms/genetics , Neoplastic Processes
12.
Pathol Res Pract ; 256: 155257, 2024 Apr.
Article En | MEDLINE | ID: mdl-38537524

Circular RNAs (circRNAs) constitute a recently identified category of closed continuous loop RNA transcripts, serving as a subset of competing endogenous RNAs (ceRNAs) with the capacity to modulate genes by acting as microRNA sponges. In the context of cancer growth, numerous investigations have explored the potential functions of circRNAs, revealing their diverse functions either as oncogenes, promoting cancer progression, or as tumor suppressors, mitigating disease development. Among these, circRNA ADAM9 (Circ-ADAM9) is now recognized as an important player in a variety of mechanisms, both physiological and pathological, especially in cancer. The aberrant expression of Circ-ADAM9 has been observed across multiple human malignancies, implying a significant involvement in tumorigenesis. This comprehensive review aims to synthesize recent findings elucidating the function of Circ-ADAM9 in many malignancies. Additionally, the review explores the possibility of Circ-ADAM9 as a valuable biomarker, offering insights into its prognostic, diagnostic, and therapeutic implications. By summarizing the latest discoveries in this field, the review contributes to our understanding of the multifaceted contribution of Circ-ADAM9 in tumor biology and its potential applications in clinical settings.


MicroRNAs , Neoplasms , Humans , RNA, Circular/genetics , Neoplasms/genetics , MicroRNAs/genetics , Carcinogenesis/genetics , Cell Transformation, Neoplastic , Membrane Proteins/genetics , ADAM Proteins
13.
Pathol Res Pract ; 255: 155157, 2024 Mar.
Article En | MEDLINE | ID: mdl-38320440

Lung cancer (LCs) is still a serious health problem globally, with many incidences attributed to environmental triggers such as Volatile Organic Compounds (VOCs). VOCs are a broad class of compounds that can be released via various sources, including industrial operations, automobile emissions, and indoor air pollution. VOC exposure has been linked to an elevated risk of lung cancer via multiple routes. These chemicals can be chemically converted into hazardous intermediate molecules, resulting in DNA damage and genetic alterations. VOCs can also cause oxidative stress, inflammation, and a breakdown in the cellular protective antioxidant framework, all of which contribute to the growth of lung cancer. Moreover, VOCs have been reported to alter critical biological reactions such as cell growth, apoptosis, and angiogenesis, leading to tumor development and metastasis. Epidemiological investigations have found a link between certain VOCs and a higher probability of LCs. Benzene, formaldehyde, and polycyclic aromatic hydrocarbons (PAHs) are some of the most well-researched VOCs, with comprehensive data confirming their cancer-causing potential. Nevertheless, the possible health concerns linked with many more VOCs and their combined use remain unknown, necessitating further research. Identifying the toxicological consequences of VOCs in LCs is critical for establishing focused preventative tactics and therapeutic strategies. Better legislation and monitoring mechanisms can limit VOC contamination in occupational and environmental contexts, possibly reducing the prevalence of LCs. Developing VOC exposure indicators and analyzing their associations with genetic susceptibility characteristics may also aid in early identification and targeted therapies.


Air Pollutants , Air Pollution, Indoor , Lung Neoplasms , Volatile Organic Compounds , Humans , Volatile Organic Compounds/adverse effects , Volatile Organic Compounds/analysis , Air Pollutants/adverse effects , Air Pollutants/analysis , Environmental Monitoring/methods , Air Pollution, Indoor/adverse effects , Air Pollution, Indoor/analysis
14.
Pathol Res Pract ; 255: 155186, 2024 Mar.
Article En | MEDLINE | ID: mdl-38350169

Osteomyelitis, a debilitating bone infection, presents considerable clinical challenges due to its intricate etiology and limited treatment options. Despite strides in surgical and chemotherapeutic interventions, the treatment landscape for osteomyelitis remains unsatisfactory. Recent attention has focused on the role of non-coding RNAs (ncRNAs) in the pathogenesis and progression of osteomyelitis. This review consolidates current knowledge on the involvement of distinct classes of ncRNAs, including microRNAs, long ncRNAs, and circular RNAs, in the context of osteomyelitis. Emerging evidence from various studies underscores the potential of ncRNAs in orchestrating gene expression and influencing the differentiation of osteoblasts and osteoclasts, pivotal processes in bone formation. The review initiates by elucidating the regulatory functions of ncRNAs in fundamental cellular processes such as inflammation, immune response, and bone remodeling, pivotal in osteomyelitis pathology. It delves into the intricate network of interactions between ncRNAs and their target genes, illuminating how dysregulation contributes to the establishment and persistence of osteomyelitic infections. Understanding their regulatory roles may pave the way for targeted diagnostic tools and innovative therapeutic interventions, promising a paradigm shift in the clinical approach to this challenging condition. Additionally, we delve into the promising therapeutic applications of these molecules, envisioning novel diagnostic and treatment approaches to enhance the management of this challenging bone infection.


MicroRNAs , Osteomyelitis , RNA, Long Noncoding , Humans , RNA, Untranslated/genetics , Osteomyelitis/genetics , Inflammation
15.
ACS Appl Mater Interfaces ; 16(8): 9736-9748, 2024 Feb 28.
Article En | MEDLINE | ID: mdl-38349780

Polymeric micelles have been extensively studied as vectors for the delivery of hydrophobic drugs for the treatment of cancers and other diseases. Despite intensive research, few formulations provide significant benefits, and even fewer have been clinically approved. While many traditional non-responsive micelles have excellent safety profiles, they lack the ability to respond to the intracellular environment and release their cargo in a spatiotemporally defined manner to effectively deliver large doses of cytotoxic drugs into the cytosol of cells that overwhelm efflux pumps. As a novel and adaptable strategy, we hypothesized that well-established non-responsive polymeric micelles could be augmented with a pH-trigger via the co-encapsulation of cytocompatible oligoelectrolytes, which would allow rapid cargo release in the endosome, leading to increased cytotoxicity. Herein, we demonstrate how this strategy can be applied to render non-responsive micelles pH-responsive, resulting in abrupt cargo release at specific and tunable pH values compatible with endosomal delivery, which significantly increased their cytotoxicity up to 3-fold in an ovarian adenocarcinoma (SKOV-3) cell line compared to non-responsive micelles. In comparison, the oligoelectrolyte-loaded micelles were significantly less toxic to healthy 3T3 fibroblasts, indicating a selective cargo release in cancer cell lines. Oligoelectrolytes can be co-encapsulated in the micelles along with drugs at high encapsulation efficiency percentages, which are both ejected from the micelle core upon oligoelectrolyte ionization. Mechanistically, the increase in cytotoxicity appears to also result from the accelerated endosomal escape of the cargo caused by disruption of the endosomal membrane by the simultaneous release of the oligoelectrolytes from the micelles. Furthermore, we show how this approach is broadly applicable to non-responsive micelles regardless of their composition and various classes of hydrophobic chemotherapeutics. The preliminary studies presented here reveal the versatility and wide scope of oligoelectrolyte-mediated, pH-triggered drug release as a compelling and powerful strategy to enhance the cytotoxicity of non-responsive polymeric micelles.


Antineoplastic Agents , Neoplasms , Humans , Micelles , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Drug Carriers/chemistry , Polymers/chemistry , Neoplasms/drug therapy , Hydrogen-Ion Concentration , Drug Liberation , Doxorubicin/chemistry
16.
EXCLI J ; 23: 34-52, 2024.
Article En | MEDLINE | ID: mdl-38343745

This review delves into the pivotal role of the long non-coding RNA NEAT1 in cancer biology, particularly in lung cancer (LC). It emphasizes NEAT1's unique subcellular localization and active involvement in gene regulation and chromatin remodeling. The review highlights NEAT1's impact on LC development and progression, including cell processes such as proliferation, migration, invasion, and resistance to therapy, positioning it as a potential diagnostic marker and therapeutic target. The complex web of NEAT1's regulatory interactions with proteins and microRNAs is explored, alongside challenges in targeting it therapeutically. The review concludes optimistically, suggesting future avenues for research and personalized LC therapies, shedding light on NEAT1's crucial role in LC. See also the Graphical abstract(Fig. 1).

17.
Sci Rep ; 14(1): 2246, 2024 01 26.
Article En | MEDLINE | ID: mdl-38278862

The increasing antimicrobial resistance in Providencia stuartii (P. stuartii) worldwide, particularly concerning for immunocompromised and burn patients, has raised concern in Bangladesh, where the significance of this infectious opportunistic pathogen had been previously overlooked, prompting a need for investigation. The two strains of P. stuartii (P. stuartii SHNIBPS63 and P. stuartii SHNIBPS71) isolated from wound swab of two critically injured burn patients were found to be multidrug-resistant and P. stuartii SHNIBPS63 showed resistance to all the 22 antibiotics tested as well as revealed the co-existence of blaVEB-6 (Class A), blaNDM-1 (Class B), blaOXA-10 (Class D) beta lactamase genes. Complete resistance to carbapenems through the production of NDM-1, is indicative of an alarming situation as carbapenems are considered to be the last line antibiotic to combat this pathogen. Both isolates displayed strong biofilm-forming abilities and exhibited resistance to copper, zinc, and iron, in addition to carrying multiple genes associated with metal resistance and the formation of biofilms. The study also encompassed a pangenome analysis utilizing a dataset of eighty-six publicly available P. stuartii genomes (n = 86), revealing evidence of an open or expanding pangenome for P. stuartii. Also, an extensive genome-wide analysis of all the P. stuartii genomes revealed a concerning global prevalence of diverse antimicrobial resistance genes, with a particular alarm raised over the abundance of carbapenem resistance gene blaNDM-1. Additionally, this study highlighted the notable genetic diversity within P. stuartii, significant informations about phylogenomic relationships and ancestry, as well as potential for cross-species transmission, raising important implications for public health and microbial adaptation across different environments.


Burns , Communicable Diseases , Enterobacteriaceae Infections , Providencia , Wound Infection , Humans , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Bangladesh , Plasmids , Drug Resistance, Multiple, Bacterial/genetics , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Communicable Diseases/drug therapy , Carbapenems , Genomics , Burns/drug therapy , Wound Infection/drug therapy , Microbial Sensitivity Tests
18.
Nutrition ; 120: 112334, 2024 Apr.
Article En | MEDLINE | ID: mdl-38271761

BACKGROUND: In Pakistan, the incidence of colorectal cancer (CRC) has sharply increased in recent years. Although several studies have reported global risk factors for CRC, no study has been conducted in Khyber Pakhtunkhwa (KPK), Pakistan, to investigate the risk factors associated with the increased CRC burden in this population. OBJECTIVES: Therefore, we conducted a clinical survey using a case-control study design to explore the risk factors associatd with CRC. METHODS: In the present study, one control was enrolled for each case. Both cases and controls were asked to complete a questionnaire to gather data. We analyzed all data using SPSS. RESULTS: Our study found that certain dietary factors, such as consuming fast food (OR: 3.0; P = 0.0001) and reusing ghee (OR: 2.45; P = 0.0001) and oil (OR: 4.30; P = 0.0001), increase the risk of CRC. Additionally, use of tobacco products like smoking cigarettes (OR: 1.91; P = 0.0001) and using snuff (OR: 3.72; P = 0.0001) significantly increases the risk of CRC. Certain habitual factors, including binge eating (OR: 2.42; P = 0.0001) and spending excessive time watching TV (OR: 1.98; P = 0.0001), also increase the odds of developing CRC. However, our study also identified some protective factors against CRC, such as consuming vegetables (OR: .41; P = 0.0001), developing healthy eating habits (OR: .61; P = 0.0001), and maintaining regular sleeping patterns (OR: .45; P = 0.0001). CONCLUSION: Given these findings, targeted health education is necessary to prevent the increase in CRC in this area. We also recommend developing and enforcing appropriate control guidelines for cancer risk factors to curb the incidence of CRC.


Colorectal Neoplasms , Humans , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology , Colorectal Neoplasms/prevention & control , Case-Control Studies , Diet/adverse effects , Risk Factors , Vegetables
19.
Rev Med Virol ; 34(1): e2491, 2024 Jan.
Article En | MEDLINE | ID: mdl-37985599

The immunopathology of herpes simplex virus (HSV)-associated neuroinflammation is a captivating and intricate field of study within the scientific community. HSV, renowned for its latent infection capability, gives rise to a spectrum of neurological expressions, ranging from mild symptoms to severe encephalitis. The enigmatic interplay between the virus and the host's immune responses profoundly shapes the outcome of these infections. This review delves into the multifaceted immune reactions triggered by HSV within neural tissues, intricately encompassing the interplay between innate and adaptive immunity. Furthermore, this analysis delves into the delicate equilibrium between immune defence and the potential for immunopathology-induced neural damage. It meticulously dissects the roles of diverse immune cells, cytokines, and chemokines, unravelling the intricacies of neuroinflammation modulation and its subsequent effects. By exploring HSV's immune manipulation and exploitation mechanisms, this review endeavours to unveil the enigmas surrounding the immunopathology of HSV-associated neuroinflammation. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of HSV infections.


Herpes Simplex , Simplexvirus , Humans , Neuroinflammatory Diseases , Adaptive Immunity , Cytokines
20.
J Glob Antimicrob Resist ; 36: 83-95, 2024 Mar.
Article En | MEDLINE | ID: mdl-38122983

OBJECTIVES: Pseudomonas aeruginosa (P. aeruginosa) stands out as a key culprit in the colonization of burn wounds, instigating grave infections of heightened severity. In this study, we have performed comparative whole genome analysis of a difficult to treat extensively drug resistant P. aeruginosa isolated from a burn patient in order to elucidate genomic diversity, molecular patterns, mechanisms and genes responsible for conferring antimicrobial resistance and virulence. METHOD: P. aeruginosa SHNIBPS206 was isolated from an infected burn wound of a critically injured burn patient. Whole genome sequencing was carried out and annotated with Prokka. Sequence type, serotype, antimicrobial resistance genes and mechanisms, virulence genes, metal resistance genes and CRISPR/Cas systems were investigated. Later, pangenome analysis was carried out to find out genomic diversity. RESULT: P. aeruginosa SHNIBPS206 (MLST 357, Serotype O11) was resistant to 14 antibiotics including carbapenems and harboured all four classes of beta lactamase producing genes: Class A (blaPME-1, blaVEB-9), Class B (blaNDM-1), Class C (blaPDC-11) and Class D (blaOXA-846). Mutational analysis of Porin D gave valuable insights. Several efflux pump, virulence and metal resistance genes were also detected. Pangenome analysis revealed high genomic diversity among different strains of P. aeruginosa. CONCLUSION: To our knowledge, this is the first report of an extensively drug resistant ST 357 P. aeruginosa from Bangladesh, which is an epidemic high-risk P. aeruginosa clone. Further research and in-depth comprehensive studies are required to investigate the prevalence of such high-risk clone of P. aeruginosa in Bangladesh.


Burns , Pseudomonas Infections , Humans , beta-Lactamases/genetics , Pseudomonas aeruginosa , Bangladesh , Multilocus Sequence Typing , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Pseudomonas Infections/epidemiology , Burns/complications
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