Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge, as malignant cells ...use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and the encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer, presents novel nanomedicine therapeutics aimed at improving the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for the clinical application of nanomedicine in the management of LC resistance.
Renewed interest towards natural substances has been pushed by the widespread diffusion of antibiotic resistance. Curcumin I is the most active and effective constituent of curcuminoids extracted ...from
Curcuma longa
and, among other beneficial effects, attracted attention for its antimicrobial potential. Since the poor pharmacokinetic profile hinders its efficient utilization, in the present paper, we report encapsulation of curcumin I in poly(styrene-co-maleic acid) (SMA-CUR) providing a nanomicellar system with improved aqueous solubility and bioavailability. SMA-CUR was characterized by means of size, zeta potential, polydispersity index, atomic force microscopy (AFM), drug release studies, spectroscopic properties and stability. SMA-CUR nanoformulation displayed exciting antimicrobial properties compared to free curcumin I towards Gram-positive and Gram-negative clinical isolates.
Renewed interest towards natural substances has been pushed by the widespread diffusion of antibiotic resistance.
The present work aims at design and synthesis of a congeneric series of small hybrids
5
and
6a-i
featuring the privileged quinoline scaffold tethered with 2-(arylamido)cinnamide moiety as potential ...anticancer tubulin polymerization inhibitors. Most of the synthesized hybrids
5
and
6a-i
significantly inhibited the growth of the HepG2 cell line, with IC
50
ranged from 2.46 to 41.31 μM. In particular, 2-(3,4,5-trimethoxybenzamido)-4-methoxycinnamide-quinoline hybrid
6e
displayed potent IC
50
value toward the examined cell line, and hence chosen for further mechanistic investigations. It is noteworthy that the antiproliferative action of compound
6e
highly correlated well with its ability to inhibit tubulin polymerization. In addition, the most potent hybrid
6e
demonstrated a significant modification in the cellular cycle distribution, in addition to provoke of apoptotic death within the tested HepG2 cell line. Furthermore, the mechanistic approach was confirmed by a substantial upregulation in the quantity of active
c
aspase 9 by 5.81-fold relative to untreated control cells.
A sequence of novel quinoline-8-yloxy and cinnamide hybrids has been synthesized and evaluated for
in vitro
cytotoxicity against HepG2 liver cancer cells.
Both personalized medicine and nanomedicine are new to medical practice. Nanomedicine is an application of the advances of nanotechnology in medicine and is being integrated into diagnostic and ...therapeutic tools to manage an array of medical conditions. On the other hand, personalized medicine, which is also referred to as precision medicine, is a novel concept that aims to individualize/customize therapeutic management based on the personal attributes of the patient to overcome blanket treatment that is only efficient in a subset of patients, leaving others with either ineffective treatment or treatment that results in significant toxicity. Novel nanomedicines have been employed in the treatment of several diseases, which can be adapted to each patient-specific case according to their genetic profiles. In this review, we discuss both areas and the intersection between the two emerging scientific domains. The review focuses on the current situation in personalized medicine, the advantages that can be offered by nanomedicine to personalized medicine, and the application of nanoconstructs in the diagnosis of genetic variability that can identify the right drug for the right patient. Finally, we touch upon the challenges in both fields towards the translation of nano-personalized medicine.
Colorectal cancer (CRC) is the third most common cancer affecting people. The discovery of new, non-invasive, specific, and sensitive molecular biomarkers for CRC may assist in the diagnosis and ...support therapeutic decision making. Exosomal miRNAs have been demonstrated in carcinogenesis and CRC development, which makes these miRNAs strong biomarkers for CRC. Deep sequencing allows a robust high-throughput informatics investigation of the types and abundance of exosomal miRNAs. Thus, exosomal miRNAs can be efficiently examined as diagnostic biomarkers for disease screening. In the present study, a number of 660 mature miRNAs were detected in patients diagnosed with CRC at different stages. Of which, 29 miRNAs were differentially expressed in CRC patients compared with healthy controls. Twenty-nine miRNAs with high abundance levels were further selected for subsequent analysis. These miRNAs were either highly up-regulated (e.g., let-7a-5p, let-7c-5p, let-7f-5p, let-7d-3p, miR-423-5p, miR-3184-5p, and miR-584) or down-regulated (e.g., miR-30a-5p, miR-99-5p, miR-150-5p, miR-26-5p and miR-204-5p). These miRNAs influence critical genes in CRC, leading to either tumor growth or suppression. Most of the reported diagnostic exosomal miRNAs were shown to be circulating in blood serum. The latter is a novel miRNA that was found in exosomal profile of blood serum. Some of the predicted target genes of highly expressed miRNAs participate in several cancer pathways, including CRC pathway. These target genes include tumor suppressor genes, oncogenes and DNA repair genes. Main focus was given to multiple critical signaling cross-talking pathways including transforming growth factor β (TGFβ) signaling pathways that are directly linked to CRC. In conclusion, we recommend further analysis in order to experimentally confirm exact relationships between selected differentially expressed miRNAs and their predicted target genes and downstream functional consequences.
Traditional treatments for head and neck squamous cell carcinoma (HNSCC) such as surgery, radiation therapy, and chemotherapy, often have severe side effects. Local delivery of chemotherapeutic ...agents can be a promising approach to minimise systemic toxicity and improve efficacy. Lauric acid (LA), was explored as a novel injectable thermosensitive drug reservoir as a depot for sustained release of anticancer drugs to treat HNSCC. LA was characterised in terms of melting temperature and gelation time. The efficacy of LA-based drug formulations was tested
in a HNSCC cell line and
in a mouse model of HNSCC. LA was modified to have a melting point of 38.5 °C and a gelation time of 40 s at 37.5 °C, rendering it suitable for injection at body temperature. LA- based doxorubicin (DOXO) formulation showed slow release with a maximum of 18% release after 3 days. The
study showed that LA enhanced the cytotoxic effect of DOXO. LA combined with DOXO prevented tumour progression and LA alone significantly reduced the original tumour volume compared to the untreated control group. These findings confirmed that LA can function as practical carrier for the local delivery of chemotherapeutics and provides a safe and simple strategy for the delivery of hydrophobic anticancer drugs and warrant further testing in clinical trials.
Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the path for the emerging field of nanomedicine to become a powerful tool in the fight against cancer. ...Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for the treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 has been reported in lung, colon, metastatic breast cancers, and bladder squamous carcinoma. Moreover, sildenafil has been reported to increase the sensitivity of tumor cells of different origins to the cytotoxic effect of chemotherapeutic agents with augmented apoptosis mediated through inducing the downregulation of Bcl-xL and FAP-1 expression, enhancing reactive oxygen species (ROS) generation, phosphorylating BAD and Bcl-2, upregulating caspase-3,8,9 activities, and blocking cells at G0/G1 cell cycle phase. Sildenafil has also demonstrated inhibitory effects on the efflux activity of ATP-binding cassette (ABC) transporters such as ABCC4, ABCC5, ABCB1, and ABCG2, ultimately reversing multidrug resistance. Accordingly, there has been a growing interest in using sildenafil as monotherapy or chemoadjuvant in EPR augmentation and management of different types of cancer. In this review, we critically examine the basic molecular mechanism of sildenafil related to cancer biology and discuss the overall potential of sildenafil in enhancing EPR-based anticancer drug delivery, pointing to the outcomes of the most important related preclinical and clinical studies.
A new series of cinnamide-fluorinated derivatives has been synthesized and characterized by using different spectroscopic and elemental microanalyses methods. All of the prepared p-fluorocinnamide ...derivatives were evaluated for their cytotoxic activity against the HepG2 liver cancerous cell line. The imidazolone derivative 6, which bears N-(N-pyrimidin-2-ylbenzenesulphamoyl) moiety, displayed antiproliferative activity against HepG2 liver cancerous cells with an IC50 value of 4.23 μM as compared to staurosporin (STU) (IC50 = 5.59 μM). In addition, compound 6 experienced epidermal growth factor receptor (EGFR) inhibitory activity comparable to palatinib. The cell cycle analysis by flow cytometry indicated that compound 6 arrested the cellular cycle of HepG2 cells at the G1 phase. Additionally, as demonstrated by the fluorescence-activated cell sorting (FACS) technique, compound 6 increased both early and late apoptotic ratios compared to control untreated HepG2 cells. Moreover, imidazolone compound 6 induced apoptosis via the intrinsic apoptotic pathway by decreasing the level of mitochondrial membrane polarization (MMP) compared to untreated HepG2 cells. Therefore, the new N-(N-pyrimidin-2-ylbenzenesulphamoyl)imidazolone derivative 6 could be considered a potential platform for further optimizing an antitumor agent against hepatocellular carcinoma.
Cutaneous Leishmaniasis (CL) is a vector-borne skin infection that remains prevalent in regions with poor socioeconomic conditions. Stigmatization occurs when individuals with physical or ...psychological disorders interact with societal stereotypes. The aim of this study was to explore the perceived social stigma surrounding CL among people residing in Hubuna, Saudi Arabia.
This cross-sectional community-based survey recruited 618 individuals aged 18 years and above using the snowball sampling technique to reach hidden cases within the target population. Data was collected using a self-administered questionnaire and the Explanatory Model Interview Catalogue for Perceived Social Stigma (EMIC-SS-12) was used to assess the level of perceived social stigma. It includes questions on demographic variables, behaviors, and experiences. The analysis was performed using SPSS.
The study included 618 participants, the majority of whom were women and girls (54.2%), with a mean age of 28 ± 12.7 years. The median score for perceived social stigma was 26.0. Only 2.1% (n = 13) of participants had the highest EMIC-SS-12 score of 36, while 7.6% (n = 47) scored zero. The mean score for overall perceived social stigma was 1.89 ± 0.91, while the mean score for experienced stigma was 1.99 ± 1.02. Univariate analysis showed that sex, employment, location of lesions, and number of lesions were insignificantly associated with stigmatization (P-value < 0.05), because these associations were uncertain because the CI includes or very close to 1.
The study reveals insights into stigmatization associated with CL in the Habuna area of Saudi Arabia. It found that the median of perceived social stigma was 26. Factors such as sex, employment status, and location of the lesion are uncertainly associated with stigma. It is crucial to explore negative behaviors and perceptions and develop suitable health education programs.
Background: Out-of-wedlock childbearing is a global phenomenon that has lifelong consequences on the lives of both mothers and their children. The aim of this study is to identify the ...sociodemographic characteristics, causes, and consequences of outof- wedlock pregnancy among single mothers in Khartoum, Sudan.Methods: This descriptive, cross-sectional study was conducted at the Mygoma Orphanage Center (MOC) and Shamaa Rehabilitation Center (SRC) using convenience sampling among 200 participants. A validated questionnaire with 25 items was used to collect data. The data were entered into Epi-Data Manager and analyzed using the SPSS. Results: The study found that most of the single mothers in Khartoum who gave birth out of wedlock were young and had just completed their university education. Most of them discovered their pregnancy during the second or third trimester, and nearly half of them did not receive any antenatal care. The majority of the children born to these mothers were preterm and had a low birth weight. Additionally, many mothers reported experiencing social stigma and rejection from their families due to their out-of-wedlock pregnancy. The study also highlighted loneliness, stress, and romantic relations as the main causes of out-of-wedlock pregnancy among single mothers in Khartoum, Sudan.Conclusion: The study provides useful insights into the sociodemographic characteristics, causes, and consequences of out-of-wedlock pregnancy among single mothers in Khartoum, Sudan. Social stigma and lack of support were identified as significant barriers to the reintegration of single mothers and their children into society. Future research should focus on investigating the long-term effects of outof- wedlock pregnancy on mothers and their children.