Redefining the battle against colorectal cancer: a comprehensive review of emerging immunotherapies and their clinical efficacy.

Colorectal cancer (CRC) is the third most common cancer globally and presents a significant challenge owing to its high mortality rate and the limitations of traditional treatment options such as surgery, radiotherapy, and chemotherapy. While these treatments are foundational, they are often poorly effective owing to tumor resistance. Immunotherapy is a groundbreaking alternative that has recently emerged and offers new hope for success by exploiting the body's own immune system. This article aims to provide an extensive review of clinical trials evaluating the efficacy of various immunotherapies, including CRC vaccines, chimeric antigen receptor T-cell therapies, and immune checkpoint inhibitors. We also discuss combining CRC vaccines with monoclonal antibodies, delve into preclinical studies of novel cancer vaccines, and assess the impact of these treatment methods on patient outcomes. This review seeks to provide a deeper understanding of the current state of CRC treatment by evaluating innovative treatments and their potential to redefine the prognosis of patients with CRC.

Occurrence of antibiotics and antibiotic-resistant bacteria in the Lebanese polluted Litani River.

Antibiotic contamination in polluted rivers is well recognized as an environmental and public health challenge. In this study, the occurrence, distribution, and ecological risk assessment of three commonly used antibiotics (amoxicillin, ciprofloxacin, and azithromycin) were assessed in the Litani River, the most important and highly polluted river in Lebanon. Physicochemical and microbiological water quality parameters including the antibiotic-resistant ones were in parallel determined in the same sites. Water samples from five sites stretching across the river upper basin were analyzed for the antibiotics under study using high-performance liquid chromatography, with both fluorometric and UV detectors post-extraction using a solid-phase method with a hydrophilic-lipophilic balance cartridges. The disc diffusion method and standardized water quality methods were used for antibiotic-resistant bacteria and water quality assessment, respectively. Amoxicillin and ciprofloxacin were found at concentrations of 250 ng/L and 107.2 ng/L, while azithromycin was not detected in any of the sites under study. Varying levels of antibiotic resistance were detected with the isolated Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) while the total coliforms showed resistance to multiple antibiotics. COD, TP, PO43-, TN, NO3-, NH4 + , E. coli, total coliform, P. aeruginosa, and Cd levels surpassed permissible levels. Correlation analysis with water quality parameters (COD, total phosphate, phosphate, total nitrogen, and cadmium) showed a significant positive correlation with ciprofloxacin (r > 0.5, p value < 0.05). Also, the resistant P. aeruginosa showed a significant positive correlation with cadmium (r > 0.5, p value < 0.05) while the resistant E. coli was positively correlated with total nitrogen, nitrate, and lead levels (r > 0.5, p value < 0.05). The ecological risk assessment revealed that all the tested antibiotics pose low risks (ecological risk quotient RQ < 0.1) except ciprofloxacin, which could pose a medium risk (0.1 < RQ < 1). Future research concerning the long-term assessment of antibiotics' residues and the identification of resistance genes in the river is recommended.

Saffron extract and crocin exert anti-inflammatory and anti-oxidative effects in a repetitive mild traumatic brain injury mouse model.

Saffron Crocus sativus L. (C. sativus) is a flower from the iridaceous family. Crocin, saffron's major constituent, and saffron have anti-oxidative and anti-inflammatory activities. In this work, the neuroprotective effects of saffron and crocin are being investigated in a repetitive mild traumatic brain injury (rmTBI) mouse model. A weight drop model setup was employed to induce mild brain injury in male albino BABL/c mice weighing 30-40 g. Saffron (50 mg/kg) and crocin (30 mg/kg) were administrated intraperitoneally 30 min before mTBI induction. Behavioral tests were conducted to assess behavioral deficits including the modified neurological severity score (NSS), Morris water maze (MWM), pole climb test, rotarod test, and adhesive test. The levels of TNF alpha (TNF-α), interferon-gamma (IFN-γ), myeloperoxidase activity (MPO), malonaldehyde (MDA), and reduced glutathione (GSH) were measured. Histological analysis of different brain parts was performed. Both saffron and crocin demonstrated marked improved neurological, cognitive, motor, and sensorimotor functions. Besides, both compounds significantly reduced the oxidative stress and inflammatory processes. No abnormal histological features were observed in any of the injured groups. Saffron extract and crocin provide a neuroprotective effect in a mouse model of rmTBI by decreasing oxidative stress, inflammatory responses, and behavioral deficits.

Saffron extract attenuates neuroinflammation in rmTBI mouse model by suppressing NLRP3 inflammasome activation via SIRT1.

Traumatic brain injury (TBI) remains a major cause of morbidity and disability worldwide and a healthcare burden. TBI is an important risk factor for neurodegenerative diseases hallmarked by exacerbated neuroinflammation. Neuroinflammation in the cerebral cortex plays a critical role in secondary injury progression following TBI. The NOD-like receptors (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a key player in initiating the inflammatory response in various central nervous system disorders entailing TBI. This current study aims to investigate the role of NLRP3 in repetitive mild traumatic brain injury (rmTBI) and identify the potential neuroprotective effect of saffron extract in regulating the NLRP3 inflammasome. 24 hours following the final injury, rmTBI causes an upregulation in mRNA levels of NLRP3, caspase-1, the apoptosis-associated speck-like protein containing a CARD (ASC), nuclear factor kappa B (NF-κB), interleukin-1Beta (IL-1ß), interleukin 18 (IL-18), nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase 1 (HMOX1). Protein levels of NLRP3, sirtuin 1 (SIRT1), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1), and neuronal nuclei (Neu N) also increased after rmTBI. Administration of saffron alleviated the degree of TBI, as evidenced by reducing the neuronal damage, astrocyte, and microglial activation. Pretreatment with saffron inhibited the activation of NLRP3, caspase-1, and ASC concurrent to reduced production of the inflammatory cytokines IL-1ß and IL-18. Additionally, saffron extract enhanced SIRT1 expression, NRF2, and HMOX1 upregulation. These results suggest that NLRP3 inflammasome activation and the subsequent inflammatory response in the mice cortex are involved in the process of rmTBI. Saffron blocked the inflammatory response and relieved TBI by activating detoxifying genes and inhibiting NLRP3 activation. The effect of saffron on the NLRP3 inflammasome may be SIRT1 and NF-κB dependent in the rmTBI model. Thus, brain injury biomarkers will help in identifying a potential therapeutic target in treating TBI-induced neurodegenerative diseases.

Nettle Tea Inhibits Growth of Acute Myeloid Leukemia Cells In Vitro by Promoting Apoptosis.

Urtica dioica (UD), commonly known as "stinging nettle", is a herbaceous flowering plant that is a widely used agent in traditional medicine worldwide. Several formulations of UD leaf extract have been reported to exhibit anti-inflammatory and antioxidant properties, with anticancer potential. The current study investigated the possible anticancer properties of nettle tea, prepared from Urtica dioica leaves, on acute myeloid leukemia (AML) cell lines, and deciphered the underlying molecular mechanisms. Treatment of AML cell lines (U-937 and KG-1) with UD aqueous leaf extract resulted in a dose- and time-dependent inhibition of proliferation, an increase in apoptotic hallmarks such as phosphatidylserine flipping to the outer membrane leaflet, and DNA fragmentation as revealed by cell-death ELISA and cell-cycle analysis assays. Apoptosis induction in U937 cells involves alterations in the expression of Bax and Bcl-2 upon exposure to nettle tea. Furthermore, the chemical composition of UD aqueous extract indicated the presence of multiple chemical agents, such as flavonoids and phenolics, mainly patuletin, m/p-hydroxybenzoic acid, and caffeic acid, among others, to which the pro-apoptotic and anti-tumor effects may be attributed.

Hepatoprotective effect of Matricaria chamomilla aqueous extract against 1,2-Dimethylhydrazine-induced carcinogenic hepatic damage in mice.

Dimethylhydrazine (DMH) is a potent colonic and hepatic carcinogen that is metabolized into oxyradicals causing liver injury and DNA mutations. Matricaria chamomilla is a well-documented medicinal herb that possesses anti-inflammatory, antioxidant and antitumor activities and is commonly used to treat diverse ailments. The present study aimed to reveal the hepatoprotective effects of Matricaria chamomilla aqueous extract during an intermediate stage of colorectal cancer (CRC) in mice. Male Balb/c mice were divided into six groups: group A served as control, group B received chamomile extract (150 mg/Kg b.w.) orally for 12 weeks, and groups C-F received weekly intraperitoneal injections of DMH (20 mg/Kg b.w.) once a week for 12 weeks. In addition to DMH, groups D and F received chamomile during the initiation and post-initiation stages, respectively. Blood and liver samples were collected for biochemical and molecular analyses. The results showed that DMH induced hepatic injury in mice as shown by significant increase in serum aspartate aminotransferase and alanine aminotransferase. The changes in biochemical parameters were accompanied by activation of the Wnt signaling pathway leading to increased hepatocytes proliferation as well as inflammation evidenced by high levels of pro-inflammatory enzymes cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). The results also showed potential hepatoprotective effects of chamomile extract against DMH-induced liver injury, proliferation and inflammation. Chamomile restored the biochemical and molecular parameters and this improvement was more pronounced in mice pretreated with the extract. In conclusion, chamomile extract may exert its hepatoprotective activities against DMH probably due to the antioxidant, antiproliferative and anti-inflammatory properties of its flavonoids.

Quantitative Analysis of Heavy Metals and Organic Compounds in Soil from Deir Kanoun Ras El Ain Dump, Lebanon.

Recently, there has been a worldwide concern regarding soil contamination by heavy metals and organic compounds, especially in the developing countries including Lebanon that has suffered from solid waste mismanagement for decades. Deir Kanoun Ras El Ain is a village in southern Lebanon that possesses one of the country's worst dumps, and its leachates influx into a running canal that irrigates surrounding agricultural lands. The aim of this study was to determine the levels of some toxic heavy metals and organic compounds in different soil samples collected from the dump and along the canal during winter and summer seasons. Six research sites (four from the dump and two along the canal) were selected, and the soil samples for analysis were collected from a depth of around 10 cm. Heavy metals (lead, cadmium, arsenic, and mercury) and organic compounds (phthalates, bisphenol A, and polyaromatic hydrocarbons) content were determined using atomic absorption and high pressure liquid chromatography, respectively. The conducted research confirmed high levels of contamination in the collected soil samples by both heavy metals and organic compounds. The present study provided evidence that different sampling sites accumulated heavy metals at concentrations that exceeded the average maximum permissible levels for sewage sludge and agricultural land. These findings suggest the need for mitigation measures by the Lebanese authorities and new waste management programs to resolve the problems associated with uncontrolled dumping of solid wastes in Lebanon.

Serum Iron and Zinc Levels in Lebanese Multiple Sclerosis Patients.

PURPOSE: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that attacks mainly the myelin sheath covering the axons of neurons. Various studies have reported a potential role of zinc and iron in MS disease. The aim of this study is to estimate the serum level of iron and zinc in Lebanese MS patients. METHODS: Sixty-nine participants were enrolled in this study, 27 were diagnosed with MS according to McDonald's criteria and 42 were normal control. Subjects were matched in age. Serum iron and zinc levels were measured using colorimetric methods. Descriptive methods and Mann-Whitney U test were used in the statistical analysis. RESULTS: The mean age of MS patients and healthy subjects was 42.8 and 38.3 years respectively. The mean serum iron level in patient and control groups was 84.7 and 83.3 µg/dl respectively. The mean serum zinc level in patient and control groups was 80.6 and 82.0 µg/dl respectively. No significant association was observed between serum iron and zinc levels in both groups. No association was also observed between serum iron and zinc levels in terms of gender. CONCLUSION: Our results showed no significant difference in serum iron and zinc levels between MS patients and healthy controls.

Preparation of curcumin-poly (allyl amine) hydrochloride based nanocapsules: Piperine in nanocapsules accelerates encapsulation and release of curcumin and effectiveness against colon cancer cells.

Curcumin (CUR) is a natural polyphenol present in the rhizomes of Curcuma longa and possesses diverse pharmacological effects, especially anti-carcinogenic effects against several types of cancers. Unfortunately, this novel compound has poor aqueous solubility and bioavailability that limit its pharmaceutical effects. The use of polymeric nanocapsules has been applied in order to overcome such problems. Thus, our present study aimed at developing two novel polymeric nanoparticles (NPs) systems that encapsulate either curcumin alone (CURN) or with piperine (CURPN), which acts as a glucuronidation inhibitor and increases the bioavailability of CUR. The NPs were successfully designed by self-assembled nanoprecipitation method and their characteristics were identified by Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), and Zeta potential analysis. The drug release profiles of NPs were monitored under different pH, and their cytotoxic effects were assessed in vitro against Caco-2 cells and in vivo against dimethylhydrazine-induced colon cancer in mice. The FTIR and XRD analyses and SEM images showed amorphous and spherical shaped CURN and CURPN of 80-100 nm sized diameter. In vitro drug release study showed that pH triggered the maximum release of CUR in basic medium compared to acidic and neutral media, and following Higuchi model. CUR nanoencapsulation enhanced its physiochemical properties and drug loading and release. In vitro and in vivo studies showed that CUR NPs exerted selective and potential cytotoxic effects against colon cancer cells. The addition of piperine facilitated the encapsulation and drug loading of CUR. Thus, CUR nanoencapsulation enhanced the solubility and bioavailability of curcumin rendering it more effective against colon cancer.

Protective effect of Matricaria chamomilla extract against 1,2-dimethylhydrazine-induced colorectal cancer in mice.

Background Colorectal cancer (CRC) is a major public health problem, with almost 1.8 million newly diagnosed cases and about 881,000 deaths annually. Chamomile (Matricaria chamomilla) is a well-documented medicinal herb that possesses anti-inflammatory and anti-carcinogenic properties. This study aimed to unravel the effect of aqueous chamomile extract against 1,2-dimethylhydrazine(DMH)-induced CRC in mice. Methods Male Balb/c mice received a weekly intraperitoneal injection of DMH (20 mg/kg body weight) for 12 weeks. Chamomile extract (150 mg/kg body weight/5 days/week p.o.) was administered at the initiation and post-initiation stages of carcinogenesis. Polyps count, histopathological analysis, real-time polymerase chain reaction (RT-PCR) analysis of Wnt signaling genes, ELISA of cyclooxygenase-2 (COX-2), and enzyme assay for inducible nitric oxide synthase (iNOS) were performed. Results Chamomile extract modulated the Wnt pathway in colonic tissues, where it significantly downregulated Wnt5a, ß-catenin, T cell factor (Tcf4), lymphoid enhancer factor 1 (Lef1), c-Myc and Cyclin D1 expression levels, while it upregulated adenomatous polyposis coli (APC) and glycogen synthase kinase (GSK3ß) expression levels. This extract significantly reduced COX-2 levels and iNOS activities. Polyps count and histopathological analysis provided supportive evidence for the biochemical and molecular analyses. Conclusions Chamomile can act as a potent dietary chemopreventive agent against DMH-induced CRC.

Oral and Dental Status of Lebanese and Syrian Refugees Living in Proximity to Deir Kanoun Ras El Ain Dump in Lebanon.

AIMS: In this study, we aimed at investigating the oral and dental health conditions of Lebanese and Syrian refugees living in proximity to Deir Kanoun Ras El Ain dump whereby its leachates influx into a canal used for irrigation and drinking purposes. MATERIALS AND METHODS: This observational study involved oral and dental examinations of 589 Lebanese and Syrian Refugees participants living in the three villages: Deir Kanoun Ras El Ain, Klayleh, and Smaiyeh. Differences in oral and dental examination results were analyzed between different villages, sexes, nationalities, and age groups. Correlation tests were conducted between dental fluorosis, staining, papilla swelling, and several sociodemographic factors. RESULTS: Dental fluorosis, staining, and papilla swelling were the most prominent problems among total participants. The highest percentages of individuals with the studied diseases were shown to be in Klayleh village, among females, and individuals aged between 21 and 40 years. Significant associations were observed between dental fluorosis and nationality; between dental staining and gender, nationality, age, and smoking; as well as between papilla swelling and age, smoking, and diabetes. CONCLUSIONS: Our study investigated and highlighted the prevalence of several oral and dental diseases among Lebanese and Syrian inhabitants that are related to environmental, social, and economic determinants and not just by individual behaviors. It also showed gaps of oral and dental health knowledge that recommend implementing health systems that focus on preventing oral diseases.

Heavy metals and organic compounds contamination in leachates collected from Deir Kanoun Ras El Ain dump and its adjacent canal in South Lebanon.

Environmental pollution generated from uncontrolled dumping is a major problem in Lebanon due to the lack of proper waste management plans. Deir Kanoun Ras El Ain is the village that harbors the worst dumps in Lebanon. Wastewater leachates of this dump influx into an adjacent nearby canal used for irrigation and drinking purposes. The aim of this study is to assess the concentrations of heavy metals (Pb, Cd, As, and Hg) and the presence of organic compounds (phthalates, bisphenol A, and polycyclic aromatic hydrocarbons (PAHs)) in water samples collected from two different sites around the dump and two canal sites during winter and summer seasons. The concentrations of heavy metals were determined using atomic absorption spectrophotometry, while the identification of the extracted organic compounds was performed using High Performance Liquid Chromatography coupled to Mass Spectrometry (HPLC-MS). The carried analyses revealed that water samples collected from dump and canal were heavily polluted by Cd, As, Hg, phthalates, bisphenol A, and PAHs caused by pyrogenic and petrogenic sources. The concentrations of the found heavy metals were far above the maximum tolerable levels set by different guidelines. The findings suggest that the studied water sources are not safe for irrigation and drinking. The serious implications of dumping wastes on the health of inhabitants recall for an immediate employment of efficient waste management policies to resolve this problem.

New variants in beta globin gene among the Palestinian refugees with sickle cell disease in Lebanon.

OBJECTIVES: To examine the association between beta-globin sequence variations and phenotypes of sickle-cell disease (SCD) complications among Palestinian refugees in Lebanon correlating them with chromatographic readings and co-inheritance with ß-thalassemia traits.   Methods: This cross-sectional study included 47 Palestinian refugees aged 4 to 54 living in different regions in Lebanon during the year 2015. Participant filled a well-designed questionnaire. Deoxyribonucleic acid (DNA) was purified from the blood collected from all participants, followed by polymerase chain reaction (PCR) amplification of exon 1, exon 2, and IVS 1 of hemoglobin beta. Multiple sequence alignment for comparative analysis was performed against normal hemoglobin sequences. Results: In addition to well-known SCD mutations, rare beta globin variations were identified. Participants with these variations have phenotypic thalassemia despite the absence of known ß-thalassemia mutations.  Conclusion: The genetic variation seen among our study population is correlated with reduced beta globin transcription, and phenotypic ß-thalassemia complications among SCD patients under study.

Effect of Ocimum basilicum leaves extract on acetaminophen-induced nephrotoxicity in BALB/c mice.

Background Acetaminophen (APAP) is one of the most widely used drugs to treat pain. Its overdose is lethal causing liver and kidney failure. Nephrotoxicity and hepatotoxicity are mostly due to the overproduction of reactive oxygen species. Ocimum basilicum, known as basil, is a commonly used medicinal plant due to its versatile role as antibacterial, antifungal, and anti-oxidative. We aim in this study to investigate the preventive and protective effect of basil leaves aqueous extract against APAP-induced hepatorenal toxicity in BALB/c mice. Methods Acute kidney injury (AKI) was induced in mice using APAP. Mice were treated with basils extract pre and post AKI induction. Kidney and liver functions were assessed by measuring creatinine, urea, alanine transaminase, and aspartate transaminase levels in serum. Superoxide dismutase, catalase (CAT), and malondialdehyde levels of renal and hepatic tissues were assayed using Elisa. Kidney injury molecule (KIM-1) was quantified in kidney homogenate. Histopathological analysis of kidney and liver were examined. Results Significant increase in all serum parameters, in hepatic and renal MDA, and in renal KIM-1 levels was observed post AKI induction. Treatment with basils post AKI induction minimized APAP damage by reducing serum markers and MDA in both organs and by increasing SOD and CAT. However, pretreatment with basils extract caused additional increase in serum ALT and AST and MDA in liver, with a significant increase in renal antioxidant enzymes. These results were confirmed by histopathological examination. Conclusion Basil extract may act as a natural antioxidant to treat APAP-induced acute hepato-renal toxicity when used as a post-treatment.