Hormonal orchestra: mastering mitochondria's role in health and disease.

Mitochondria is a subcellular organelle involved in the pathogenesis of cellular stress, immune responses, differentiation, metabolic disorders, aging, and death by regulating process of fission, fusion, mitophagy, and transport. However, an increased interest in mitochondria as powerhouse for ATP production, the mechanisms of mitochondria-mediated cellular dysfunction in response to hormonal interaction remains unknown. Mitochondrial matrix contains chaperones and proteases that regulate intrinsic apoptosis pathway through pro-apoptotic Bcl-2 family's proteins Bax/Bak, and Cyt C release, and induces caspase-dependent and independent cells death. Energy and growth regulators such as thyroid hormones have profound effect on mitochondrial inner membrane protein and lipid compositions, ATP production by regulating oxidative phosphorylation system. Mitochondria contain cholesterol side-chain cleavage enzyme, P450scc, ferredoxin, and ferredoxin reductase providing an essential site for steroid hormones biosynthesis. In line with this, neurohormones such as oxytocin, vasopressin, and melatonin are correlated with mitochondrial integrity, displaying therapeutic implications for inflammatory and immune responses. Melatonin's also displayed protective role against oxidative stress and mitochondrial synthesis of ROS, suggesting a defense mechanism against aging-related diseases. An imbalance in mitochondrial bioenergetics can cause neurodegenerative disorders, cardiovascular diseases, and cancers. Hormone-induced PGC-1α stimulates mitochondrial biogenesis via activation of NRF1 and NRF2, which in turn triggers mtTFA in brown adipose and cardiac myocytes. Mitochondria can be transferred through cells merging, exosome-mediated transfer, and tunneling through nanotubes. By delineating the underlying molecular mechanism of hormonal mitochondrial interaction, this study reviews the dynamics mechanisms of mitochondria and its effects on cellular level, health, diseases, and therapeutic strategies targeting mitochondrial diseases.

Camptothecin-loaded mesoporous silica nanoparticles functionalized with CpG oligodeoxynucleotide as a new approach for skin cancer treatment.

The therapeutic efficacy of camptothecin (CPT), a potent antitumor alkaloid, is hindered by its hydrophobic nature and instability, limiting its clinical use in treating cutaneous squamous cell carcinoma (SCC). This study introduces a novel nano drug delivery system (NDDS) utilizing functionalized mesoporous silica nanoparticles (FMSNs) for efficient CPT delivery. The FMSNs were loaded with CPT and subsequently coated with chitosan (CS) for enhanced stability and bioadhesion. Importantly, CpG oligodeoxynucleotide (CpG ODN) was attached onto the CS-coated FMSNs to leverage the immunostimulatory properties of CpG ODN, augmenting the chemotherapy's efficacy. The final formulation FMSN-CPT-CS-CpG displayed an average size of 241 nm and PDI of 0.316 with an encapsulation efficiency of 95 %. Comprehensive in vitro and in vivo analyses, including B16F10 cells and DMBA/TPA-induced SCC murine model, demonstrated that the FMSN-CPT-CS-CpG formulation significantly enhanced cytotoxicity against B16F10 cells and induced complete regression in 40 % of the in vivo subjects, surpassing the efficacy of standard CPT and FMSN-CPT treatments. This study highlights the potential of combining chemotherapeutic and immunotherapeutic agents in an NDDS for targeted, efficient skin cancer treatment.

Diagnostic and Therapeutic Potential of Circulating-Free DNA and Cell-Free RNA in Cancer Management.

Over time, molecular biology and genomics techniques have been developed to speed up the early diagnosis and clinical management of cancer. These therapies are often most effective when administered to the subset of malignancies harboring the target identified by molecular testing. Important advances in applying molecular testing involve circulating-free DNA (cfDNA)- and cell-free RNA (cfRNA)-based liquid biopsies for the diagnosis, prognosis, prediction, and treatment of cancer. Both cfDNA and cfRNA are sensitive and specific biomarkers for cancer detection, which have been clinically proven through multiple randomized and prospective trials. These help in cancer management based on the noninvasive evaluation of size, quantity, and point mutations, as well as copy number alterations at the tumor site. Moreover, personalized detection of ctDNA helps in adjuvant therapeutics and predicts the chances of recurrence of cancer and resistance to cancer therapy. Despite the controversial diagnostic values of cfDNA and cfRNA, many clinical trials have been completed, and the Food and Drug Administration has approved many multigene assays to detect genetic alterations in the cfDNA of cancer patients. In this review, we underpin the recent advances in the physiological roles of cfDNA and cfRNA, as well as their roles in cancer detection by highlighting recent clinical trials and their roles as prognostic and predictive markers in cancer management.

Mosquirix™ RTS, S/AS01 Vaccine Development, Immunogenicity, and Efficacy.

Malaria is a parasitic infection caused by bites from Plasmodium falciparum (P. falciparum)-infected mosquitoes with a present scale of symptoms ranging from moderate fever to neurological disorders. P. falciparum is the most lethal of the five strains of malaria, and is a major case of morbidity and mortality in endemic regions. Recent advancements in malaria diagnostic tools and prevention strategies have improved conjugation antimalarial therapies using fumigation and long-lasting insecticidal sprays, thus lowering malarial infections. Declines in the total number of infected individuals have been correlated with antimalarial drugs. Despite this, malaria remains a major health threat, affecting more than 30 million men, women, and children around the globe, and 20 percent of all children around the globe have malaria parasites in their blood. To overcome this life-threatening condition, novel therapeutic strategies, including immunization, are urgently needed to tackle this infection around the world. In line with this, the development of the RTS, S vaccine was a significant step forward in the fight against malaria. RTS, S is a vaccine for P. falciparum in which R specifies central repeat units, T the T-cell epitopes, and S indicates surface antigen. The RTS, S/AS01 malarial vaccine was synthesized and screened in several clinical trials between 2009 and 2014, involving thousands of young children in seven African countries, showing that children who received the vaccine did not suffer from severe malaria. Mosquirix™ was approved by the World Health Organization in 2021, indicating it to be safe and advocating its integration into routine immunization programs and existing malaria control measures. This paper examines the various stages of the vaccine's development, including the evaluation of its immunogenicity and efficacy on the basis of a total of 2.3 million administered doses through a routine immunization program. The protection and effectiveness provided by the vaccine are strong, and evidence shows that it can be effectively delivered through the routine child immunization platform. The economic cost of the vaccine remains to be considered.

Biological Potentials and Phytochemical Constituents of Raw and Roasted Nigella arvensis and Nigella sativa.

Nigella species are widely used to cure various ailments. Their health benefits, particularly from the seed oils, could be attributed to the presence of a variety of bioactive components. Roasting is a critical process that has historically been used to facilitate oil extraction and enhance flavor; it may also alter the chemical composition and biological properties of the Nigella seed. The aim of this study was to investigate the effect of the roasting process on the composition of the bioactive components and the biological activities of Nigella arvensis and Nigella sativa seed extracts. Our preliminary study showed that seeds roasted at 50 °C exhibited potent antimicrobial activities; therefore, this temperature was selected for roasting Nigella seeds. For extraction, raw and roasted seed samples were macerated in methanol. The antimicrobial activities against Streptococcus agalactiae, Streptococcus epidermidis, Streptococcus pyogenes, Candida albicans, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, and Klebsiella oxytoca were determined by measuring the diameter of the zone of inhibition. The cell viability of extracts was tested in a colon carcinoma cell line, HCT-116, by using a microculture tetrazolium technique (MTT) assay. Amino acids were extracted and quantified using an automatic amino acid analyzer. Then, gas chromatography-mass spectrometry (GC-MS) analysis was performed to identify the chemical constituents and fatty acids. As a result, the extracts of raw and roasted seeds in both Nigella species showed strong inhibition against Klebsiella oxytoca, and the raw seed extract of N.arvensis demonstrated moderate inhibition against S. pyogenes. The findings of the MTT assay indicated that all the extracts significantly decreased cancer cell viability. Moreover, N. sativa species possessed higher contents of the measured amino acids, except tyrosine, cystine, and methionine. The GC-MS analysis of extracts showed the presence of 22 and 13 compounds in raw and roasted N. arvensis, respectively, and 9 and 11 compounds in raw and roasted N. sativa, respectively. However, heat treatment decreased the detectable components to 13 compounds in roasted N. arvensis and increased them in roasted N. sativa. These findings indicate that N. arvensis and N. sativa could be potential sources of anticancer and antimicrobials, where the bioactive compounds play a pivotal role as functional components.

Thymus Gland: A Double Edge Sword for Coronaviruses.

The thymus is the main lymphoid organ that regulates the immune and endocrine systems by controlling thymic cell proliferation and differentiation. The gland is a primary lymphoid organ responsible for generating mature T cells into CD4+ or CD8+ single-positive (SP) T cells, contributing to cellular immunity. Regarding humoral immunity, the thymic plasma cells almost exclusively secrete IgG1 and IgG3, the two main complement-fixing effector IgG subclasses. Deformity in the thymus can lead to inflammatory diseases. Hassall's corpuscles' epithelial lining produces thymic stromal lymphopoietin, which induces differentiation of CDs thymocytes into regulatory T cells within the thymus medulla. Thymic B lymphocytes produce immunoglobulins and immunoregulating hormones, including thymosin. Modulation in T cell and naive T cells decrement due to thymus deformity induce alteration in the secretion of various inflammatory factors, resulting in multiple diseases. Influenza virus activates thymic CD4+ CD8+ thymocytes and a large amount of IFNγ. IFNs limit virus spread, enhance macrophages' phagocytosis, and promote the natural killer cell restriction activity against infected cells. Th2 lymphocytes-produced cytokine IL-4 can bind to antiviral INFγ, decreasing the cell susceptibility and downregulating viral receptors. COVID-19 epitopes (S, M, and N proteins) with ≥90% identity to the SARS-CoV sequence have been predicted. These epitopes trigger immunity for antibodies production. Boosting the immune system by improving thymus function can be a therapeutic strategy for preventing virus-related diseases. This review aims to summarize the endocrine-immunoregulatory functions of the thymus and the underlying mechanisms in the prevention of COVID-19.

Inhibition of NF-κB signaling and HSP70/HSP90 proteins by newly synthesized hydrazide derivatives in arthritis model.

In the current study, the N-benzylidene-4-((2-hydroxynaphthalene-1-yl) diazenyl) hydrazides (NCHDH and NTHDH) were evaluated against the Carrageenan- and CFA-induced models. During the preliminary investigation, the NCHDH and NTHDH treatment showed marked anti-inflammatory and analgesic activity against the Carrageenan-induced acute model. Once the anti-inflammatory activity was established against acute Carrageenan model, the NCHDH and NTHDH were evaluated against the chronic CFA-induced arthritis model. The NCHDH and NTHDH treatment markedly attenuated the inflammatory and analgesic parameters compared to CFA-treated group. Furthermore, the increase in the oxidative stress and attenuation of antioxidant enzymes has been reported following CFA administration. However, NCHDH and NTHDH treatment significantly induced the antioxidants and attenuated the oxidative stress markers. The CFA administration showed marked tailing of DNA; however, the NCHDH- and NTHDH-treated group preserved DNA integrity. Furthermore, the histological studies showed marked alteration in the CFA-treated group; however, the NCHDH and NTHDH treatment markedly improved the histological features. The Western blot, immunohistology, and ELISA assay revealed marked increase in the Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Jun N-terminal Kinase (JNK), TNF-α, and COX-2 levels; however, the NCHDH and NTHDH attenuated their expressions significantly. Similarly, the NCHDH and NTHDH significantly induced the mRNA expression levels of heat shock proteins. The computational analysis showed significant binding interaction with various protein targets via multiple hydrogens, and hydrophobic bonds. The in vivo pharmacokinetic study was also performed to assess the various pharmacokinetic parameters. In conclusion, the NCHDH and NTHDH treatment showed significant anti-arthritic activity against Carrageenan and CFA models.

Evaluation and docking of indole sulfonamide as a potent inhibitor of α-glucosidase enzyme in streptozotocin -induced diabetic albino wistar rats.

We have synthesized new hybrid class of indole bearing sulfonamide scaffolds (1-17) as α-glucosidase inhibitors. All scaffolds were found to be active except scaffold 17 and exhibited IC50 values ranging from 1.60 to 51.20 µM in comparison with standard acarbose (IC50 = 42.45 µM). Among the synthesized hybrid class scaffolds 16 was the most potent analogue with IC50 value 1.60 µM, showing many folds better potency as compared to standard acarbose. Whereas, synthesized scaffolds 1-15 showed good α-glucosidase inhibitory potential. Based on α-glucosidase inhibitory effect, Scaffold 16 was chosen due to highest activity in vitro for further evaluation of antidiabetic activity in Streptozotocin induced diabetic rats. The Scaffold 16 exhibited significant antidiabetic activity. All analogues were characterized through 1H, 13CNMR and HR MS. Structure-activity relationship of synthesized analogues was established and confirmed through molecular docking study.

Extracellular vesicles in cancer diagnostics and therapeutics.

Cancer promotion, development, and malignant transformation is greatly influenced by cell-to-cell interactions in a complex tissue microenvironment. Cancer and stromal cells secrete soluble factors, as well as deport membrane-encapsulated structures, which actively contribute and mediate cell-to-cell interaction within a tumor microenvironment (TME). These membrane structures are recognized as extracellular vesicles (EVs), which include exosomes and microvesicles. They can carry and transport regulatory molecules such as oncogenic proteins, coding and non-coding RNAs, DNA, and lipids between neighboring cells and to distant sites. EVs mediate crucial pathophysiological effects such as the formation of premetastatic niches and the progression of malignancies. There is compelling evidence that cancer cells exhibit a significant amount of EVs, which can be released into the surrounding body fluids, compared with nonmalignant cells. EVs therefore have the potential to be used as disease indicator for the diagnosis and prognosis of cancers, as well as for facilitating research into the underlying mechanism and biomolecular basis of these diseases. Because of their ability to transport substances, followed by their distinct immunogenicity and biocompatibility, EVs have been used to carry therapeutically-active molecules such as RNAs, proteins, short and long peptides, and various forms of drugs. In this paper, we summarize new advancement in the biogenesis and physiological roles of EVs, and underpin their functional impacts in the process of cancer growth and metastasis. We further highlight the therapeutic roles of EVs in the treatment, prevention, and diagnosis of human malignancies.

A review on recent advances and applications of fish collagen.

During the processing of the fishery resources, the significant portion is either discarded or used to produce low-value fish meal and oil. However, the discarded portion is the rich source of valuable proteins such as collagen, vitamins, minerals, and other bioactive compounds. Collagen is a vital protein in the living body as a component of a fibrous structural protein in the extracellular matrix, connective tissue and building block of bones, tendons, skin, hair, nails, cartilage and joints. In recent years, the use of fish collagen as an increasingly valuable biomaterial has drawn considerable attention from biomedical researchers, owing to its enhanced physicochemical properties, stability and mechanical strength, biocompatibility and biodegradability. This review focuses on summarizing the growing role of fish collagen for biomedical applications. Similarly, the recent advances in various biomedical applications of fish collagen, including wound healing, tissue engineering and regeneration, drug delivery, cell culture and other therapeutic applications, are discussed in detail. These applications signify the commercial importance of fish collagen for the fishing industry, food processors and biomedical sector.

Potential applications of bacterial cellulose and its composites for cancer treatment.

Bacterial cellulose (BC) has received immense interest in medical, pharmaceutical, and other related fields owing to its intrinsic physical, mechanical, and biological features. Its structural features offer an ideal environment for developing composites, thereby further extending its areas of applications. BC was initially used in wound dressing, artificial blood vessels, organ development, and tissue regeneration; however, the recent focus has switched to 3D printing techniques. BC can serve as suitable material for treating different cancers due to unique liquid absorbing and drug loading properties. BC-based scaffolds have been synthesized and tested for in vitro culturing of cancer cells to simulate tumor microenvironments. These scaffolds support normal growth of cancer cells, particularly breast and ovarian cancer cells, showing significant adhesion, proliferation, ingrowth, and differentiation. This review describes the different approaches of manipulating BC for use in medicine, with particular focus on the applications of BC composites in cancer treatment. A detailed discussion about various formulations of BC in multiple cancer therapeutics is summarized.

Nanocurcumin: A Double-Edged Sword for Microcancers.

There is compelling evidence that drug molecules isolated from natural sources are hindered by low systemic bioavailability, poor absorption, and rapid elimination from the human body. Novel approaches are urgently needed that could enhance the retention time as well as the efficacy of natural products in the body. Among the various adopted approaches to meet this ever-increasing demand, nanoformulations show the most fascinating way of improving the bioavailability of dietary phytochemicals through modifying their pharmacokinetics and pharmacodynamics. Curcumin, a yellowish pigment isolated from dried ground rhizomes of turmeric, exhibits tremendous pharmacological effects, including anticancer activities. Several in vitro and in vivo studies have shown that curcumin mediates anticancer effects through the modulation (upregulation and/or downregulations) of several intracellular signaling pathways both at protein and mRNA levels. Scientists have introduced multiple modern techniques and novel dosage forms for enhancing the delivery, bioavailability, and efficacy of curcumin in the treatment of various malignancies. These novel dosage forms include nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles. Nanocurcumin has shown improved anticancer effects compared to conventional curcumin formulations. This review discusses the underlying molecular mechanism of various nanoformulations of curcumin for the treatment of different cancers. We hope that this study will make a road map for preclinical and clinical investigations of cancer and recommend nano curcumin as a drug of choice for cancer therapy.

An Update on the Role of Dietary Phytochemicals in Human Skin Cancer: New Insights into Molecular Mechanisms.

Human skin is continuously subjected to environmental stresses, as well as extrinsic and intrinsic noxious agents. Although skin adopts various molecular mechanisms to maintain homeostasis, excessive and repeated stresses can overwhelm these systems, leading to serious cutaneous damage, including both melanoma and non-melanoma skin cancers. Phytochemicals present in the diet possess the desirable effects of protecting the skin from damaging free radicals as well as other benefits. Dietary phytochemicals appear to be effective in preventing skin cancer and are inexpensive, widely available, and well tolerated. Multiple in vitro and in vivo studies have demonstrated the significant anti-inflammatory, antioxidant, and anti-angiogenic characteristics of dietary phytochemicals against skin malignancy. Moreover, dietary phytochemicals affect multiple important cellular processes including cell cycle, angiogenesis, and metastasis to control skin cancer progression. Herein, we discuss the advantages of key dietary phytochemicals in whole fruits and vegetables, their bioavailability, and underlying molecular mechanisms for preventing skin cancer. Current challenges and future prospects for research are also reviewed. To date, most of the chemoprevention investigations have been conducted preclinically, and additional clinical trials are required to conform and validate the preclinical results in humans.

Bacillus amyloliquefaciens RWL-1 as a New Potential Strain for Augmenting Biochemical and Nutritional Composition of Fermented Soybean.

Soybean (Glycine max L.) is a good source of natural antioxidants and commonly consumed as fermented products such as cheonggukjang, miso, tempeh, and sufu in Asian countries. The aim of the current study was to examine the influence of novel endophytic bacterial strain, Bacillus amyloliquefaciens RWL-1 as a starter for soybean fermentation. During fermentation, the cooked soybeans were inoculated with different concentrations (1%, 3%, and 5%) of B. amyloliquefaciens RWL-1. The changes in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activities, total phenolic contents, isoflavones (Daidzin, Genistin, Glycitin, Daidzein, Glycitein, and Genistein), amino acids (aspartic acid, threonine, serine, glutamic acid, glycine, alanine, cysteine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, and proline) composition, and minerals (calcium, copper, iron, potassium, magnesium, manganese, sodium, nickel, lead, arsenic, and zinc) were investigated. The level of antioxidants, total phenolic contents, isoflavones, and total amino acids were higher in fermented soybean inoculated with 1% B. amyloliquefaciens RWL-1 after 60 h of fermentation as compared to control, 3% and 5% B. amyloliquefaciens RWL-1. Additionally, fermented soybean inoculated with 5% B. amyloliquefaciens RWL-1 showed the highest values for mineral contents. Changes in antioxidant activities and bioactive compounds depended on the concentration of the strain used for fermentation. From these results, we conclude that fermented soybean has strong antioxidant activity, probably due to its increased total phenolic contents and aglycone isoflavone that resulted from fermentation. Such natural antioxidants could be used in drug and food industries and can be considered to alleviate oxidative stress.

Anti-epileptic activity of daidzin in PTZ-induced mice model by targeting oxidative stress and BDNF/VEGF signaling.

Epilepsy is a complex and multifactorial neurodegenerative disease described by recurrent seizures. Oxidative stress and dysregulation of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) are critical factors for the development of epilepsy. Daidzin is well-known for its effective anti-inflammatory and antioxidant potential for centuries. The present study was focused on exploring the anti-epileptic potential of daidzin in the pentylenetetrazole-induced mice model. Daidzin (1, 5, and 10 mg/kg) was administered in the acute study and the dose was optimized. Pretreatment with daidzin remarkably reduced the severity of epileptogenesis in a dose-dependent manner. Moreover, chronic epilepsy was induced in mice by administration of PTZ (35 mg/kg, i.p) every alternative day for 21 days. Results demonstrated that daidzin significantly prevented epileptogenesis and reversed histopathological changes in the hippocampus. It remarkably improved antioxidant (glutathione, glutathione sulfotransferase, superoxide dismutase, and catalase) levels while decreased MDA (malondialdehyde) and nitrite production in the brain. It remarkably improved the expressions of heme oxygenase-1 (HO-1) and BDNF while reduced the expression of VEGF. It remarkably prevented the neuronal apoptosis in the brain tissue. Additionally, spectroscopic analysis such as FTIR (Fourier transform infrared spectroscopy) and DSC (differential scanning calorimetry) revealed that daidzin remarkably prevented PTZ-induced protein damage. HPLC-UV spectrophotometry results demonstrated that there was no peak of aglycone daidzin (metabolite) in the brain sample which specify that the anticonvulsant effect of the compound is due to its direct entry into the brain tissue. Moreover, the molecular docking results showed that daidzin possesses a better binding affinity for ALDH2, estrogen receptor-ß, P13k, AKT2, mTORC1, and HIF-1-α proteins. Taken together, the results of the present study showed that daidzin has remarkable neuroprotective and anti-epileptic properties through modulation of oxidative stress, BDNF/VEGF, and apoptotic signaling in the brain tissue of PTZ-kindled mice.

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders.

Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs' entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices.

Lirioresinol B dimethyl ether inhibits NF-κB and COX-2 and activates IκBα expression in CCl4-induced hepatic fibrosis.

BACKGROUND: Inflammation is one of the key components in the initiation and progression of hepatic diseases. If not treated, inflammation may cause cell dysplasia, and ultimately cancer. In the current study, we investigated the anti-inflammatory and anti-cancer activities of plant isolated compound Lirioresinol B Dimethyl Ether (LBDE) extracted from the seeds of Magnolia fargesii CHENG (Magnoliaceae) against HepG2 cells as well as in BALB/C male mice. METHODS: We assessed the antioxidant and anti-proliferative effects of plant compounds using DPPH assay and HepG2 cell lines. Carbon tetrachloride (CCl4) and Diethylnitrosamine (DEN) were used to induce liver cell dysplasia followed by hepatocellular carcinoma (HCC) in BALB/C male mice for 12 weeks. We investigated the underlying mechanism by using histopathology and immunoblot experiments. RESULTS: Intraperitoneal injection of LBDE (50 mg/kg body weight/day) inhibited CCl4-induced HCC. Free radical scavenging assay shows the strong anti-oxidant activity of LBDE. Western blot results show that LBDE down-regulated nuclear factor kappa B (NFκB) and cyclooxygenase (COX-2) by preventing the phosphorylation of I kappa B alpha (IκBα) in CCl4 treated group. LBDE also improved liver function by decreasing Alkaline Phosphatase (ALP), aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) levels. Histopathology results revealed that LBDE decreased granulomas and express normal morphology of hepatocytes. CONCLUSIONS: These preliminary results show that LBDE has the potential to inhibit CCl4-induced liver cell dysplasia and prevents cancer development by regulating NFκB/COX-2 activation.

Solvent and temperature effects of accelerated solvent extraction (ASE) coupled with ultra-high pressure liquid chromatography (UHPLC-DAD) technique for determination of thymoquinone in commercial food samples of black seeds (Nigella sativa).

Black seeds (Nigella sativa), is considered a traditional folk medicine in Saudi Arabia where it is widely available in the form of food supplements with limited information warranting its quality. This study aims to develop an effective and reliable method of black seeds evaluation and standardization in terms of Thymoquinone (THQ), obtained from various geographical sources i.e. Pakistan (PK), Saudi Arabia (SA) and India (I). Accelerated solvent extraction (ASE) was utilized for the first time to extract whereas Ultra High pressure liquid chromatography (UHPLC-DAD) was used to quantify THQ. Inductively coupled plasma mass spectrometry (ICP-MS) was used for elemental analysis of the samples. An ideal temperature (70 °C) and solvent (n-hexane) with extraction yield of 97.30% ±â€¯3.98 was observed. In the case of commercial food samples an extraction yield and %recovery within a short time (42 ±â€¯2 min) using least amount of solvent (49.5 ±â€¯2 ml) was observed; SA (18.22 g; 91.1%)  > PK (17.32 g; 86.6%)  > I (16.33 g; 81.65%). UHPLC resulted a RT of 3.29 min for THQ with concentration (ng/ml) in the samples as; SA, 34410.36 > PK, 7778.95 > I, 4106.43. Elemental analysis revealed an order of SA > I > PK for tested elements. ASE resulted a high extract yield as compared to traditional methods of extraction whereas ASE-UHPLC/DAD showed a rapid and sensitive method of THQ quantification and quality determination in market available food samples for black seeds.

Application of Three-dimensional (3D) Tumor Cell Culture Systems and Mechanism of Drug Resistance.

The in-vitro experimental model for the development of cancer therapeutics has always been challenging. Recently, the scientific revolution has improved cell culturing techniques by applying three dimensional (3D) culture system, which provides a similar physiologically relevant in-vivo model for studying various diseases including cancer. In particular, cancer cells exhibiting in-vivo behavior in a model of 3D cell culture is a more accurate cell culture model to test the effectiveness of anticancer drugs or characterization of cancer cells in comparison with two dimensional (2D) monolayer. This study underpins various factors that cause resistance to anticancer drugs in forms of spheroids in 3D in-vitro cell culture and also outlines key challenges and possible solutions for the future development of these systems.