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Pharmacological studies indicated that Ocimum basilicum L. var. thyrsiflora has numerous therapeutic potentials. The aim of this study was to investigate the neuroprotective action of O. basilicum leaf extract against scopolamine-induced non-spatial memory deficits in rats and to determine the changes in mRNA expressions of genes implicated in cognition and neuroprotection. O. basilicum leaves were extracted with 80% ethanol and verified for the presence of rosmarinic acid using high performance liquid chromatography method. Male Wistar rats were treated orally with either O. basilicum or the positive control piracetam for 14 days prior to the injection of 0.5 mg/kg scopolamine on the day of the novel object discrimination (NOD) test. Hippocampi were collected at the end of the test. mRNA expression of nicotinic acetylcholine α7 subunit (NA7), muscarinic M1 receptor (M1), neuronal nitric oxide synthase (nNOS), and 5-hydroxytryptamine receptor 3A (HTR3A) genes in the hippocampi were analyzed using qPCR method. The presence of rosmarinic acid in the plant extract was detected at chromatogram peak of Rt=16.891. NOD test results indicated that the lower dose of O. basilicum (200 mg/kg) significantly (p

The birch tree-derived pentacyclic lupine type-triterpenoid Betulinic acid has demonstrated a variety of biological activities BetA is known for its harmlessness on normal healthy cells. However, recent investigations have indicated that BetA can cause cellular changes in mouse normal embryonic fibroblasts even with a minimal concentration. This report cautioned the use of BetA at the clinical level, which encouraged us to examine whether BetA could produce any key effect on normal healthy cells of any organs in mice. The present study extended its investigation to evaluate whether BetA could induce any changes in the renal system and the expression pattern of NADPH-diaphorase an indirect marker of the enzyme nitric oxide synthase in mice. Our results indicated that BetA exposure induced NADPH-d expression in both organs without causing any significant morphological changes. Moreover, NADPH-d activity patterns in the organs of BetA-treated animals tremendously increased (from day 4 until day 12) when compared to controls. The expression of NADPH-d in both the kidney and bladder implies that NADPH-d-mediated nitric oxide signaling could be a mechanism involved in BetA-induced nephroprotection. These outcomes are of direct clinical importance and could pay the way for the improvement of BetA as an important pharmaceutical product.

Over centuries, Moringa oleifera has been used as an integral part of Ayurveda, Siddha and Unani systems of medicine, besides this miracle tree has a wide range of nutritional and bioactive compounds, including proteins, essential amino acids, carbohydrates, lipids, fiber, vitamins, minerals, phenolic compounds, phytosterols and others. The miracle tree is endowed with a wide range of pharmacological properties, including anti-diabetic, anti-inflammatory, anti-carcinogenic, antioxidant, cardioprotective, antimicrobial and hepatoprotective activities. However, deeper dimensions of authentic data on plant based natural products in relation to drug discovery, pharmacokinetics properties of biomolecules is far lacking. ADMET prospecting is eventually expected to contribute to success of MO based lead candidates in drug design, development program besides saving time and money. This study is the first of its kind reporting summative ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicology) properties of all bioactive compounds Moringa oleifera methanolic pod extract (MOMPE) as a potential source of natural drug lead using Swiss ADME. A total of 12 compounds namely - 7-Octadecyne, 2-methyl- (C19H36); 3,7,11,15-Tetramethyl-2-hexadecen-1-ol (C20H40O); 3,7,11,15-Tetramethyl-2-hexadecen-1-ol (C20H40O); 6,9,12,15-Docosatetraenoic acid, me (C23H38O2); Cyclohexanol, 5-methyl-2-(1-methylethyl)- (C10H20O); 3,7,11,15-Tetramethyl-2-hexadecen-1-ol (C20H40O); Palmitic acid vinyl ester (C18H34O2); .γ.-Tocopherol (C28H48O2); Vitamin E (C29H50O2); Cholesta-7,9(11)-dien-3-ol, 4,4-dim (C29H48O); γ.-Sitosterol (C29H50O); Stigmasta-5,24(28)-dien-3-ol, (3.β.,24Z)- (C29H48O). Most of the MOPBNPs are non-substrate for both P-gp (P-glycoprotein) and CYP (Cytochrome P-450 isoenzymes). All the compounds were evaluated for properties viz., GI absorption, BBB permeant, Pgp substrate, CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4 inhibitors, Lipinski, Ghose, Veber, Egan, Muegge, rule and Bioavailability Score to provide baseline information on PBNPs in MONRD pod. Keywords: PBNPs; NGDDT; ADMET; Moringa oleifera; Secondary Metabolites MONRD pod

Moringa oleifera has been reported to be the store-house of wide range of bioactive compounds. Most commonly used plant part has been the leaves which are reported to be rich in Vitamins, Carotenoids, Polyphenols, Phenolic Acids, Flavonoids Alkaloids, Glucosinolates, Isocyanides, Tannins and Saponins. Moringa leaves are used as Keerai while, green pods are commonly used as vegetable in the traditional preparation of Sambar in South-India. MO is gaining popularity because of its nutrient-rich root, leaves, flowers and fruits, having immense traditional medicinal uses and proved pharmacological properties. Not much of work has been carried out on analysis of bioactive compounds present in the pods. In the present study an attempt has been made to screen and analyze the range of bioactive compounds present in Moringa oleifera seed removed ripened natural dried pods. Phytochemical screening and GCMS analysis revealed the presence of 12 compounds namely - 7-Octadecyne, 2-methyl- (C19H36); 3,7,11,15-Tetramethyl-2-hexadecen-1-ol (C20H40O); 3,7,11,15-Tetramethyl-2-hexadecen-1-ol (C20H40O); 6,9,12,15-Docosatetraenoic acid, me (C23H38O2); Cyclohexanol, 5-methyl-2-(1-methylethyl)- (C10H20O); 3,7,11,15-Tetramethyl-2-hexadecen-1-ol (C20H40O); Palmitic acid vinyl ester (C18H34O2); .gamma.-Tocopherol (C28H48O2); Vitamin E (C29H50O2); Cholesta-7,9(11)-dien-3-ol, 4,4-dim (C29H48O); gamma.-Sitosterol (C29H50O); Stigmasta-5,24(28)-dien-3-ol, (3.beta.,24Z)- (C29H48O). Further, in-silico ADMET analysis is expected to provide in-death physiochemical and biomolecular details of these molecules in order to exploit them for production of novel drugs for the pharma market with wide array of bio medical applications. Keywords: Bioactive Compounds; GCMS; Phytochemical Screening; MOPME; Plant Based Natural Products

Supplementary Table 2 from Genome-Wide Promoter Analysis of the SOX4 Transcriptional Network in Prostate Cancer Cells

Supplementary Table 3 from Genome-Wide Promoter Analysis of the SOX4 Transcriptional Network in Prostate Cancer Cells

Supplementary Table 6 from Genome-Wide Promoter Analysis of the SOX4 Transcriptional Network in Prostate Cancer Cells

Supplementary Table 7 from Genome-Wide Promoter Analysis of the SOX4 Transcriptional Network in Prostate Cancer Cells

SOX4 is a critical developmental transcription factor in vertebrates and is required for precise differentiation and proliferation in multiple tissues. In addition, SOX4 is overexpressed in many human malignancies, but the exact role of SOX4 in cancer progression is not well understood. Here, we have identified the direct transcriptional targets of SOX4 using a combination of genome-wide localization chromatin immunoprecipitation–chip analysis and transient overexpression followed by expression profiling in a prostate cancer model cell line. We have also used protein-binding microarrays to derive a novel SOX4-specific position-weight matrix and determined that SOX4 binding sites are enriched in SOX4-bound promoter regions. Direct transcriptional targets of SOX4 include several key cellular regulators, such as EGFR, HSP70, Tenascin C, Frizzled-5, Patched-1, and Delta-like 1. We also show that SOX4 targets 23 transcription factors, such as MLL, FOXA1, ZNF281, and NKX3-1. In addition, SOX4 directly regulates expression of three components of the RNA-induced silencing complex, namely Dicer, Argonaute 1, and RNA Helicase A. These data provide new insights into how SOX4 affects developmental signaling pathways and how these changes may influence cancer progression via regulation of gene networks involved in microRNA processing, transcriptional regulation, the TGFβ, Wnt, Hedgehog, and Notch pathways, growth factor signaling, and tumor metastasis. [Cancer Res 2009;69(2):709–17]

Supplementary Figure and Methods from Sex-Determining Region Y Box 4 Is a Transforming Oncogene in Human Prostate Cancer Cells

Supplementary Table 5 from Genome-Wide Promoter Analysis of the SOX4 Transcriptional Network in Prostate Cancer Cells

Supplementary Table 4 from Genome-Wide Promoter Analysis of the SOX4 Transcriptional Network in Prostate Cancer Cells

Supplementary Table S1 from Sex-Determining Region Y Box 4 Is a Transforming Oncogene in Human Prostate Cancer Cells

Supplementary Methods, Figure Legends 1-6 from Genome-Wide Promoter Analysis of the SOX4 Transcriptional Network in Prostate Cancer Cells

Prostate cancer is the most commonly diagnosed noncutaneous neoplasm and second most common cause of cancer-related mortality in western men. To investigate the mechanisms of prostate cancer development and progression, we did expression profiling of human prostate cancer and benign tissues. We show that the SOX4 is overexpressed in prostate tumor samples compared with benign tissues by microarray analysis, real-time PCR, and immunohistochemistry. We also show that SOX4 expression is highly correlated with Gleason score at the mRNA and protein level using tissue microarrays. Genes affected by SOX4 expression were also identified, including BCL10, CSF1, and NcoA4/ARA70. TLE-1 and BBC3/PUMA were identified as direct targets of SOX4. Silencing of SOX4 by small interfering RNA transfection induced apoptosis of prostate cancer cells, suggesting that SOX4 could be a therapeutic target for prostate cancer. Stable transfection of SOX4 into nontransformed prostate cells enabled colony formation in soft agar, suggesting that, in the proper cellular context, SOX4 can be a transforming oncogene. (Cancer Res 2006; 66(8): 4011-9)

Supplementary Table 1 from Genome-Wide Promoter Analysis of the SOX4 Transcriptional Network in Prostate Cancer Cells

Supplementary Figures 1-6 from Genome-Wide Promoter Analysis of the SOX4 Transcriptional Network in Prostate Cancer Cells

BACKGROUND: In recent years, low back pain (LBP) is a growing major health issue around the world and mostly addressed in primary healthcare settings. This may be due to changing work environment including the nature of long sitting work hours, especially in the booming information and technology (IT) and Business Process Outsourcing (BPO) industry. LBP is normally considered as a combination of various types of pain and its related conditions, which eventually lead to disabilities. AIM: In this article, the aim is to discuss the current and future perspectives of LBP mainly on diagnosis and therapeutic front of LBP. METHODS: A search was performed using electronic databases, which include PubMed Central and Google Scholar, using the related key words “back pain and low back pain.” All related peer reviewed published articles were included regardless of the language, region, or the publication date. RESULTS: Although the management of LBP both in terms of diagnosis as well as in the therapeutic options has witnessed considerable progress but challenges are still exist not only within countries but also in the regions and continents among various medical professionals. However, in the past few years, a huge array of coordinated but randomized multi-center clinical studies were performed and various detailed insight investigations have been done, and substantial clinical guidelines have become available. Hence, a new view on evidence-based management approach for LBP has significantly improved recently and discussed here. CONCLUSION: Based on the available evidence and literature, this comprehensive review discusses the present and future perspectives of LBP mainly on diagnosis and therapeutic front for LBP. In addition, current intervention and prevention plans have failed to lessen the considerable burden of LBP and hence several areas which require more details, which deserves additional discussion to augment us through an understanding of this very important topic on improvements of multi tasked outcomes to benefit the affected patients.

Background Bioactive principles from various natural resources including medicinal herbs have always played a crucial role in healthcare settings and increasingly became key players in drug discovery and development for many biopharmaceutical applications. Additionally, natural products (NPs) have immense arrangement of distinctive chemical structures with diverse functional groups that motivated numerous investigators including synthetic chemists to discover new therapeutic entities. Numerous pre-clinical investigations involving the animal models have evident the usefulness of these NPs against various human diseases including neurodegenerative disorders (NDs). Main text Ocimum basilicum Linn (O. basilicum L.), also known as sweet basil, is well practiced in traditional healthcare systems and has been used to treat various human illnesses, which include malaria, skin disease, diarrhea, bronchitis, dysentery, arthritis, eye diseases, and insect bites and emphasize the significance of the ethno-botanical approach as a potential source of novel drug leads With the growing interest in advanced techniques, herbal medicine and medicinal plants explorations are still considered to be a novel resource for new pharmacotherapeutic discovery and development. O. basilicum L and its bioactive principles including apigenin, eugenol, myretenal, β-sitosterol, luteolin, rosmarinic acid, carnosic acid, essential oil (EO)-rich phenolic compounds, and others like anthocyanins and flavones could be of therapeutic values in NDs by exhibiting their neuro-protective efficacy on various signaling pathways. The present comprehensive review collected various related information using the following searching engines such as PubMed, Science Direct, Google Scholar, etc. and focused mainly the English written documents. The search period comprised of last two decades until present. Conclusion Although these efficacious plant genera of prime importance and has potential medical and socioeconomic importance, yet the pivotal evidence for its neuroprotective potential in novel clinical trials remains lacking. However, with the available wealth of obtainable literature on this medicinal plant, which supports this review and concludes that O. basilicum L may function as a promising therapeutics for the treatment of NDs.

BackgroundCancer is a complex and most widespread disease and its prevalence is increasing worldwide, more in countries that are witnessing urbanization and rapid industrialization changes. Although tremendous progress has been made, the interest in targeting cancer has grown rapidly every year. This review underscores the importance of preventive and therapeutic strategies.Main textNatural products (NPs) from various sources including plants have always played a crucial role in cancer treatment. In this growing list, numerous unique secondary metabolites from marine sources have added and gaining attention and became potential players in drug discovery and development for various biomedical applications. Many NPs found in nature that normally contain both pharmacological and biological activity employed in pharmaceutical industry predominantly in anticancer pharmaceuticals because of their enormous range of structure entities with unique functional groups that attract and inspire for the creation of several new drug leads through synthetic chemistry. Although terrestrial medicinal plants have been the focus for the development of NPs, however, in the last three decades, marine origins that include invertebrates, plants, algae, and bacteria have unearthed numerous novel pharmaceutical compounds, generally referred as marine NPs and are evolving continuously as discipline in the molecular targeted drug discovery with the inclusion of advanced screening tools which revolutionized and became the component of antitumor modern research.ConclusionsThis comprehensive review summarizes some important and interesting pipeline marine NPs such as Salinosporamide A, Dolastatin derivatives, Aplidine/plitidepsin (Aplidin®) and Coibamide A, their anticancer properties and describes their mechanisms of action (MoA) with their efficacy and clinical potential as they have attracted interest for potential use in the treatment of various types of cancers.

Treatment options for most cancers are still insufficient, despite developments and technology advancements. It has been postulated that the immune response to progressive tumors is insufficient due to a deficiency in afferent mechanisms responsible for the development of tumor-reactive T cells. Many patients treated for cancer will have their cancer recurrence, often after a long remission period. This suggests that there are a small number of tumor cells that remain alive after standard treatment(s) – alone or in combination and have been less effective in combating metastasis that represents the most elaborate hurdle to overcome in the cure of the disease. Therefore, any new effective and safe therapeutic agents will be highly demanded. To circumvent many plant extracts have attributed for their chemoprotective potentials and their influence on the human immune system. It is now well recognized that immunomodulation of immune response could provide an alternative or addition to conventional chemotherapy for a variety of disease conditions. However, many hurdles still exist. In recent years, there has been a tremendous interest either in harnessing the immune system or towards plant-derived immunomodulators as anticancer agents for their efficacy, safety and their targeted drug action and drug delivery mechanisms. This review discusses Phyllanthus Schum. & Thonn. their chemopreventive and immunomodulatory properties over the past few years. Although, as many as 500 important bioactive phytochemical compounds have been isolated from Phyllanthus their chemotherapeutic, immunomodulatory properties, molecular targets and modes of action are yet to be enlightened in detail. Hence, the theme of this review is very useful for further research on Phyllanthus species. because many phytochemicals from these plants have demonstrated preclinical therapeutic efficacy for a wide range of human diseases.

Background: The anticancer effects of Phyllanthus amarus extract on various cancer cells have been investigated, however, the effects of its major constituents on HCT116 human colorectal cancer cells have not been reported. Objective: In the present study, we investigated the cytotoxic effect of 80% ethanol extract of P. amarus and its marker constituents (phyllanthin, hypophyllanthin, gallic acid, niranthin, greraniin, phyltetralin, isolintetralin, corilagin and ellagic acid) on HCT116 and their underlying mechanisms of action. Methods: Their antiproliferative and apoptotic effects on HCT 116 were performed using MTT assay and flow cytometric analysis, respectively, while caspases 3/7, 8 and 9 activities were examined using the colorimetric method. The expression of cleaved poly ADP ribose polymerase enzyme (PARP) and cytochrome c proteins was investigated by the immune-blot technique. Results and Discussion: HPLC and LC-MS/MS analyses demonstrated that the extract contained mainly lignans and polyphenols. The plant samples markedly suppressed the growth and expansion of HCT116 cells in a concentration- and time-dependent manner with no toxicity against normal human fibroblast CCD18 Co. P. amarus extract, phyllanthin and gallic acid induced mode of cell death primarily through apoptosis as confirmed by the exteriorization of phosphatidylserine. Caspases 3/7, 8, and 9 activities increased in a concentration-dependent manner following 24h treatment. The expressions of cleaved PARP (Asp 214) and cytochrome c were markedly upregulated. Conclusion: P. amarus extract, phyllanthin and gallic acid exhibited an apoptotic effect on HCT116 cells through the caspases-dependent pathway.

BACKGROUND: Corneal blindness resulting from various medical conditions affects millions worldwide. The rapid developing tissue engineering field offers design of a scaffold with mechanical properties and transparency similar to that of the natural cornea. AIM: The present study aimed at to prepare and investigate the properties of PVA/chitosan blended scaffold by further cross-linking with 1-Ethyl-3-(3-dimethyl aminopropyl)-carbodiimide (EDC) and 2 N-Hydroxysuccinimide (NHS) as potential in vitro carrier for human limbal stem cells delivery. MATERIAL AND METHODS: Acetic acid dissolved chitosan was added to PVA solution, uniformly mixed with a homogenizer until the mixture was in a colloidal state, followed by H2SO4 and formaldehyde added and the sample was allowed to cool, subsequently it was poured into a tube and heated in an oven at 60°C for 50 minutes. Finally, samples were soaked in a cross-linking bath with EDC, NHS and NaOH in H2O/EtOH for 24 h consecutively stirred to cross-link the polymeric chains, reduce degradation. After soaking in the bath, the samples were carefully washed with 2% glycine aqueous solution several times to remove the remaining amount of cross-linkers, followed by washed with water to remove residual agents. Later the cross-linked scaffold subjected for various characterization and biological experiments. RESULTS: After viscosity measurement, the scaffold was observed by Fourier transform infrared (FT-IR). The water absorbency of PVA/Chitosan was increased 361% by swelling. Compression testing demonstrated that by increasing the amount of chitosan, the strength of the scaffold could be increased to 16×10−1 MPa. Our degradation results revealed by mass loss using equation shows that scaffold degraded gradually imply slow degradation. In vitro tests showed good cell proliferation and growth in the scaffold. Our assay results confirmed that the membrane could increase the cells adhesion and growth on the substrate. CONCLUSION: Hence, we strongly believe the use of this improved PVA/chitosan scaffold has potential to cut down the disadvantages of the human amniotic membrane (HAM) for corneal epithelium in ocular surface surgery and greater mechanical strength in future after successful experimentation with clinical trials.

Background Dendritic cells (DCs) are unique antigen presenting cells (APC) which play a pivotal role in immunotherapy and induction of an effective immune response against tumors. In the present study, 80% ethanol extract of Phyllanthus amarus was used to generate tumor lysate (TLY) derived from HCT 116 and MCF-7 cancer cell lines via induction of apoptosis. Monocyte-derived DCs were generated ex vivo from the adherent population of peripheral blood mononuclear cells (PBMCs). The generated TLY were used to impulse DCs to investigate its effect on their cellular immune functions including antigen presentation capacity, phagocytic activity, chemotaxis capacity, T-cell proliferation and cytokines release. Methods The effect of P. amarus-generated TLY on DCs maturation was evaluated by determination of MHC class I, II and CD 11c expression as well as the co-stimulatory molecules CD 83 and 86 by using flow cytometry. The phagocytic capacity of TLY-pulsed DCs was investigated through FITC-dextran uptake by using flow cytometry. The effect on the cytokines release including IL-12, IL-6 and IL-10 was elucidated by using ELISA. The migration capacity and T cell proliferation activity of pulsed DCs were measured. The relative gene expression levels of cytokines were determined by using qRT-PCR. The major constituents of P. amarus extract were qualitatively and quantitatively analyzed by using validated reversed-phase high performance liquid chromatography (HPLC) methods. Results P. amarus-generated TLY significantly up-regulated the expression levels of MHC class I, CD 11 c, CD 83 and 86 in pulsed DCs. The release of interleukin IL-12 and IL-6 was enhanced by TLY-DCs at a ratio of 1 DC: 3 tumor apoptotic bodies (APO), however, the release of IL-10 was suppressed. The migration ability as well as allogeneic T-cell proliferation activities of loaded DCs were significantly enhanced, but their phagocytic capacity was highly attenuated. The gene expression profiles for IL-12 and IL-6 of DCs showed increase in their mRNA gene expression in TLY pulsed DCs versus unloaded and LPS-treated only DCs. Conclusion The effect of P. amarus-generated TLY on the immune effector mechanisms of DCs verified its potential to induce an in vitro anti-tumor immune response against the recognized tumor antigen.

The chronic bed ridden patients acquire infections are the main source of alarming morbidity and mortality as their correlation with fomites. Fomites are reservoirs of drug-resistant pathogens found in the unhygienic clinical environment, which can infect patients and leading to high nosocomial infection rates and use of antimicrobial drugs. The use of and search for drugs and dietary supplements derived from plants have accelerated various therapeutic applications and obtaining new antimicrobial agents from natural resources is necessary to develop alternative drugs for safe and cost-effective health care. Hence, the objective of this research was to perform a phytochemical analysis on Chromolaena odorata and to study the antioxidant and antimicrobial activities of the ethanolic and aqueous extracts of its leaves. In this regard, phytochemicals obtained from C.odorata was investigated for their radical scavenging activity using 2, 2-diphenyl-1-picryl-hydrazyl (DPPH) assay. The phytochemical analysis revealed the presence of active ingredients such as glycosides, steroids, saponins, phenols, flavonoids, terpenoids, and tannins were categorized either as primary metabolites, such as chlorophyll, proteins, and amino acids, or as secondary metabolites, which include terpenoids and alkaloids. The ethanolic leaf extract showed a higher antioxidant activity and antibacterial properties than the aqueous extract exhibited. C. odorata leaf extracts of both ethanoloic and aqueous were subjected to an antibacterial study using the agar diffusion method. Our antibacterial results showed that the ethanolic extract could inhibit to a certain extent the growth of various human pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, and Escherichia coli. In summary, the present study highlights the significance of C. odorata leaf extracts for their antioxidant and antibacterial potentials, which explain the traditional use of the plant in animal and human medicine and cost-effective health care.

Purpose: The purpose of this study was to defining the prevalence, size of incidence of different anatomical variations of the paranasal sinus (PNS) and nasal cavity among Sudanese patients and efficacy of CT scan in disease determination. Introduction: Disease of the PNS is a global public health problem, with the only treatment option available being endoscopic surgery. Previous studies have suggested that anatomical variations of the PNS are common in different populations; however, there is little information available to verify this. Hence, the objective of the present study was to determine the prevalence of different anatomical variations of the PNS and nasal cavity among Sudanese patients who were referred by ear, nose, and throat (ENT) surgeons for a computed tomography (CT)-aided study. Methodology: The total number of patients eligible for the study was 557; of these, 51 were excluded, 317 were in the study group, and 189 were controls. The CT images were carefully reviewed and discussed with the involvement of consultant radiologists, an anatomist, and an otolaryngologist. Results: Our results showed that there was extensive pneumatization of the frontal sinus (FS) in 37% of cases, a rudimentary FS in 11%, and absence of the FS in 12%. In addition, the Keros classification showed the FS to be normal in 55%, type I in 27%, type II in 10%, type III in 6%, and type IV in only 2% of patients. A large ethmoid bulla (EB) was found in 43% of patients, but the remaining 57% had a normal ethmoid sinus. Posterior ethmoid cells showed extensive pneumatization unilaterally in 5%, and bilaterally in 3% of patients; 92% were normal. Extensive pneumatization of the sphenoid was seen in 49% of patients, while the remaining 51% had a normal sphenoid. The sphenoid septum was attached bilaterally to the internal carotid artery in 6% and unilaterally in 21% of patients. A septate sphenoid sinus (more than one septum) was found in 33% of patients; the remaining 67% were normal. A bilateral hypoplastic maxillary sinus was seen in 23%, a unilateral hypoplastic maxillary sinus in 3%, extensive pneumatization in 17%, bilateral septation in 17%, unilateral septation in 19%, Haller cells in 33%, and normal anatomy in 67% of patients. Conclusion: A CT-aided study gives good results describing anatomical variations of the PNS in the Sudanese population and to the best of our knowledge, this is the first detailed clinical report on PNS in Sudan.

Nutraceuticals are any material, either whole or in part, that may be considered a hybrid of nutrition and pharmaceuticals. This special characteristic, aside from providing good health, leads to treatment of wounds and prevention of certain diseases. Nutraceuticals have gained significant attention due to their presumed safety and promising nutritional and therapeutic outcomes. An important aspect of the use of traditional medicinal remedies in the treatment of burns and wounds is the potential to improve healing and reduce downtime in order to ease the financial burden on the affected patients and their families. Although several medicinal plants and their pharmaceutical preparations/formulations are available for wound care and management, it remains necessary to search for efficacious treatments, as certain current formulations cause adverse effects or lack efficacy. Several herbal medicines have displayed marked activity in the management of wounds, and various natural compounds/extracts have verified in vivo wound healing potential; therefore they are considered as potential drugs of natural origin. C. odorata is considered a tropical weed. It exhibits numerous relevant medicinal properties on an appreciable scale and is known in some parts of the world as a traditional medicine used to treat various ailments. Besides the above, volatile oils of the plant are considered a possible source of a nutraceutical to be used for clinical purposes. To understand its precise role as nature’s gift for healing wounds and its contribution to affordable health care, this plant must be scientifically assessed based on the available literature. This is crucial to its potential future drug design, development, and application for the treatment of wounds in both animal and human medicine and cost-effective health care.

Cancer is a diverse class of diseases characterized by uncontrolled cell growth that constitutes the greatest cause of mortality and morbidity worldwide. Despite steady progress, the treatment modalities of cancer are still insufficient. Several new concepts have emerged for therapeutic intervention in malignant diseases with the goal of identifying specific targets and overcoming resistance against current cytotoxic therapies. Many studies have reported the remarkable and significant properties of dietary plant polyphenols such as curcumin, resveratrol, flavopiridol, indirubin, magnolol, piceatannol, parthenolide, epigallocatechin gallate, and cucurbitacin as anticancer agents known for their pleiotropic effects on cancer, immune cells, and inflammation. Piceatannol, an analogue and metabolite of resveratrol, is a natural stilbene commonly found in grape skins and wine. Compared to resveratrol, this molecule exhibits superior bioactivities as an inhibitor of COX-1/2 and the CSN-associated kinase. Piceatannol is thought to be a potent natural compound with many therapeutic effects, such as the prevention of hypercholesterolemia, arrhythmia, atherosclerosis, angiogenesis, and cardiovascular diseases. It also demonstrates vasorelaxation, antioxidant, and anticancer activities. This comprehensive review summarizes the current data regarding the mechanisms of action of piceatannol, its chemopreventive properties, and its possible therapeutic potential against various types of human cancer.

Wound is a break or discontinuity in the skin or other organs instigated by either surgical procedure or by other means, whereas wound healing is the restoration of lost parts by tissue repairs and regeneration, if not addressed on time; it can lead severe infection, chronic wounds and even death. Current therapeutic options for wound healing stills a universal health challenge. Synthetic or current antimicrobial drugs are expensive, inadequate for the treatment and produce many clinical side effects. Herbal plants naturally promote wound healing however, the mechanisms underlying the wound healing process and related therapies is still in its infancy. Calotropis are perennial shrub belong to plants of the genus Asclepiadaceae used in traditional medicine. Calotropis gigantea Linn (Cg) and Calotropis procera (Cp) are two prominent members with varied pharmacological activities for the treatment for various ailments. The pharmacological activity of their various extracts has been widely studied, revealing, among others its roots and barks used as anticancer, anti-fertility, the antidote for snakebite, anti-scabietic and other parts extracts used to treat skin infections, inflammation and cardiovascular problems. Despite having many experimental supports to attract more pharmacological interest towards this genus, additional investigations are necessary in many areas for its therapeutic options. The current ample review aims at evaluating the merits and the wound healing potential of the phytocompounds obtained from various parts of Calotropis plants and their molecular role in the healing process and provide the platform for bringing to the limelight recent efforts in this efficacious multifaceted medicinal herb.

Dengue is a debilitating disease that poses a perpetual threat to human health and increases the global economic burden every year. Despite advances in medical sciences, dengue virus (DENV) infects approximately 200 million people every year. To date, no effective antiviral is valiable to treat DENV in individuals despite great efforts in accomplishing these goals. Numerous approaches have been used in the search for dengue antiviral like screening of combinatorial compounds against DENV enzymes and structure-based computational discovery. In recent years, investigators have turned their focus into medicinal plants, trying to identify compounds that can be used as dengue antiviral. Nature represents a great reservoir of potential substances that can be explored with the aim of discovering new drugs that can be either used directly as pharmaceuticals or can provide drug leads, which can be scrutinized further for the development of new anti-dengue natural product. Many previous investigations have dealt with numerous plant extracts or bioactive principles for their antiviral property as they normally considered being safer when compared to synthetic drugs. Andrographis paniculata belongs to family Acanthaceae and is generally known as ‘king of bitters’. Diverse bioactive compounds from this plant such as diterpenes, flavonoids, xanthones, noriridoides and other miscellaneous compounds have exhibited their potential as therapeutics for various chronic as well as infectious diseases. This review is based on literature review on scientific journals, books and electronic sources, which highlights the pathogenesis of DENV and describe an assortment of bioactive principles that have been possessing antiviral potential, which include dengue and discuss the therapeutic efficacy and mechanism of action of Andrographis paniculata. However, a detailed and more comprehensive clinical trial on mammalian tissues and organs is needed in future studies.

The aim of the present study was to investigate the effects of betulinic acid (BetA) on the expression and distribution pattern of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), an indirect indicator of nitric oxide (NO) synthase in the thymus and spleen of mice. Mice were randomly assigned to four main groups (n=48 per group): Experimental group (BetA), positive control group (goniothalamin), vehicle control group (dimethyl sulfoxide) and control group (without vehicle). Each group was further divided into three equal subgroups according to the treatment length (4, 8 and 12 days). BetA treatment induced the expression of NADPH-d activity in the thymus and spleen without any significant changes in the morphology of the organs. Furthermore, the expression pattern of NADPH-d in BetA-treated animals was significantly increased compared with that in the control animals. NADPH-d expression in the thymus and spleen suggests that NO signaling may be a potential mechanism underlying the BetA-induced immunomodulation in these organs. These findings are of direct clinical relevance and may contribute to the further development of BetA as a therapeutic drug.

The evaluation of crude drugs of natural origin as sources of new effective anticancer agents continues to be important due to the lack of effective anticancer drugs currently used in practice which are generally accompanied with adverse effects at different levels of severity. The aim of this concise review is to gather existing literature on anticancer potential of extracts and compounds isolated from Celastraceae species. This review covers six genera (Maytenus, Tripterygium, Hippocratea, Gymnosporia, Celastrus and Austroplenckia) belonging to this family and their 33 isolates. Studies carried out by using different cell lines have shown remarkable indication of anticancer activity, however, only a restricted number of studies have been reported using in vivo tumor models. Some of the compounds, such as triptolide, celastrol and demethylzeylasteral from T. wilfordii, have been extensively studied on their mechanisms of action due to their potent activity on various cancer cell lines. Such promising lead compounds should generate considerable interest among scientists to improve their therapeutic potential with fewer side effects by molecular modification.

An important method of drug discovery is examination of diverse life forms, including medicinal plants and natural products or bioactive compounds isolated from these sources. In cancer research, lead structures of compounds from natural sources can be used to design novel chemotherapies with enhanced biological properties. Betulinic acid (3β-hydroxy-lup-20(29)-en-28-oic acid or BetA) is a naturally occurring pentacyclic triterpene with a wide variety of biological activities, including potent antitumor properties. Non-malignant cells and normal tissues are not affected by BetA. Because BetA exerts its effects directly on the mitochondrion and triggers death of cancerous cells, it is an important alternative when certain chemotherapy drugs fail. Mitochondrion-targeted agents such as BetA hold great promise to circumvent drug resistance in human cancers. BetA is being developed by a large network of clinical trial groups with the support of the U.S. National Cancer Institute. This article discusses recent advances in research into anticancer activity of BetA, relevant modes of delivery, and the agent's therapeutic efficacy, mechanism of action, and future perspective as a pipeline anticancer drug. BetA is a potentially important agent in cancer therapeutics.

Many receptor tyrosine kinases (RTKs) can be detected in the cell nucleus, such as EGFR, HER-2, HER-3, HER-4, and fibroblast growth factor receptor. EGFR, HER-2 and HER-4 contain transactivational activity and function as transcription co-factors to activate gene promoters. High EGFR in tumor nuclei correlates with increased tumor proliferation andpoor survivalin cancerpatients. However, the mechanism bywhich cell-surfaceEGFR translocates into the cell nucleus remains largely unknown. Here, we found that EGFR co-localizes and interacts with importins a1/b1, carriersthatarecriticalformacromoleculesnuclearimport.EGFRvariantmutatedatthenuclearlocalizationsignal(NLS) is defective in associating with importins and in entering the nuclei indicating that EGFR's NLS is critical for EGFR/ importins interaction and EGFR nuclear import.Moreover, disruption of receptor internalization processusingchemicals and forced expression of dominant-negative Dynamin II mutant suppressed nuclear entry of EGFR. Additional evidences suggestaninvolvementofendosomalsortingmachineryinEGFRnucleartranslocalization.Finally,wefoundthatnuclear export of EGFR may involve CRM1 exportin as we detected EGFR/CRM1 interaction and markedly increased nuclear EGFR following exposure to leptomycin B, a CRM1 inhibitor. Collectively, these data suggest the importance of receptor endocytosis, endosomal sorting machinery, interaction with importins a1/b1, and exportin CRM1 in EGFR nuclear- cytoplasmic trafficking. Together, our work sheds light into the nature and regulation of the nuclear EGFR pathway and provides a plausible mechanism by which cells shuttle cell-surface EGFR and potentially other RTKs through the nuclear pore complex and into the nuclear compartment. J. Cell. Biochem. 98: 1570-1583, 2006. 2006 Wiley-Liss, Inc.

The cell membrane receptor ErbB-2 migrates to the nucleus. However, the mechanism of its nuclear translocation is unclear. Here, we report a novel mechanism of its nuclear localization that involves interaction with the transport receptor importin beta1, nuclear pore protein Nup358, and a host of players in endocytic internalization. Knocking down importin beta1 using small interfering RNA oligonucleotides or inactivation of small GTPase Ran by RanQ69L, a dominant-negative mutant of Ran, causes a nuclear transport defect of ErbB-2. Mutation of a putative nuclear localization signal in ErbB-2 destroys its interaction with importin beta1 and arrests nuclear translocation, while inactivation of nuclear export receptor piles up ErbB-2 within the nucleus. Additionally, blocking of internalization by a dominant-negative mutant of dynamin halts its nuclear localization. Thus, the cell membrane-embedded ErbB-2, through endocytosis using the endocytic vesicle as a vehicle, importin beta1 as a driver and Nup358 as a traffic light, migrates from the cell surface to the nucleus. This novel mechanism explains how a receptor tyrosine kinase on the cell surface can be translocated into the nucleus. This pathway may serve as a general mechanism to allow direct communication between cell surface receptors and the nucleus, and our findings thus open a new era in understanding direct trafficking between the cell membrane and nucleus.

The treatment of most cancers is still inadequate, despite tremendous steady progress in drug discovery and effective prevention. Nature is an attractive source of new therapeutics. Several medicinal plants and their biomarkers have been widely used for the treatment of cancer with less known scientific basis of their functioning. Although a wide array of plant derived active metabolites play a role in the prevention and treatment of cancer, more extensive scientific evaluation of their mechanisms is still required. Styryl-lactones are a group of secondary metabolites ubiquitous in the genusGoniothalamusthat have demonstrated to possess antiproliferative activity against cancer cells. A large body of evidence suggests that this activity is associated with the induction of apoptosis in target cells. In an effort to promote further research on the genusGoniothalamus, this review offers a broad analysis of the current knowledge onGoniothalamin(GTN) or 5, 6, dihydro-6-styryl-2-pyronone (C13H12O2), a natural occurring styryl-lactone. Therefore, it includes (i) the source of GTN and other metabolites; (ii) isolation, purification, and (iii) the molecular mechanisms of actions of GTN, especially the anticancer properties, and summarizes the role of GTN which is crucial for drug design, development, and application in future for well-being of humans.

SOX4 is a critical developmental transcription factor in vertebrates and is required for precise differentiation and proliferation in multiple tissues. In addition, SOX4 is overexpressed in many human malignancies, but the exact role of SOX4 in cancer progression is not well understood. Here, we have identified the direct transcriptional targets of SOX4 using a combination of genome-wide localization chromatin immunoprecipitation–chip analysis and transient overexpression followed by expression profiling in a prostate cancer model cell line. We have also used protein-binding microarrays to derive a novel SOX4-specific position-weight matrix and determined that SOX4 binding sites are enriched in SOX4-bound promoter regions. Direct transcriptional targets of SOX4 include several key cellular regulators, such as EGFR, HSP70, Tenascin C, Frizzled-5, Patched-1, and Delta-like 1. We also show that SOX4 targets 23 transcription factors, such as MLL, FOXA1, ZNF281, and NKX3-1. In addition, SOX4 directly regulates expression of three components of the RNA-induced silencing complex, namely Dicer, Argonaute 1, and RNA Helicase A. These data provide new insights into how SOX4 affects developmental signaling pathways and how these changes may influence cancer progression via regulation of gene networks involved in microRNA processing, transcriptional regulation, the TGFβ, Wnt, Hedgehog, and Notch pathways, growth factor signaling, and tumor metastasis. [Cancer Res 2009;69(2):709–17]

Photodynamic therapy (PDT) is a promising treatment that is approved by the US FDA for the treatment of oesophageal and lung cancer as well as for age-related macular degeneration. In this study, using standard tissue culture techniques, the photo cytotoxicity and apoptotic mechanisms of Calphostin C (Cal C), a perylenequinone microbial compound in combination with visible light dose was examined in different tumor cell lines. Our results demonstrated both a time and drug-light dose dependence in Cal-C-PDT induced photo toxicity and apoptotic cell death. The induction of apoptosis by Cal C-PDT was found to transit to necrotic cell death at higher drug and light doses. The detection of apoptosis in irradiated tumor cells was performed using various approaches including cell morphology analysis, flow cytometry [DNA fragmentation and phosphatidylserine (PS) externalization] and biochemical assays (activation of caspases). Time-course analysis of Cal C cellular uptake and distribution showed a rapid increase within the cellular compartments. The activation of caspases and nuclear fragmentation was evidenced at a maximum time point of 3 h after irradiation. By the use of specific caspase substrates, significant activation of caspase-8 and -3 was found. Mitochondrial involvement during Cal C-PDT-induced apoptosis was proven by a rapid reduction of the mitochondrial membrane potential. Furthermore, Cal C-PDT also enhanced FasL expression, which then induced Fas signalling-dependent cell death in NPC and colon cancer cell lines tested. Our results contribute to a deeper understanding of the processes involved in apoptotic cell death following photodynamic treatment with Cal C.

Gene amplification and protein overexpression of MDM2, which is often found in certain types of cancers, indicate that MDM2 plays an important role in tumorigenesis. Interestingly, several clinical reports have demonstrated that amplification of the MDM2 gene correlates with the metastatic stage. Using an antibody array assay, we identified E-cadherin as an MDM2-binding protein and confirmed that E-cadherin is a substrate for the MDM2 E3 ubiquitin ligase. We demonstrate that MDM2 interacts in vivo with E-cadherin, resulting in its ubiquitination and degradation. This regulation appears to be clinically relevant, as we found a significant correlation between high MDM2 and low E-cadherin protein levels in resected tumor specimens recovered from breast cancer patients with lymph node metastases. Ectopic expression of MDM2 in breast cancer cells was found to disrupt cell-cell contacts and enhance cell motility and invasive potential. We found that E-cadherin and MDM2 colocalized on the plasma membrane and in the early endosome, where ubiquitin moieties were attached to E-cadherin. Blocking endocytosis with dominant-negative mutants of dynamin abolished the association of MDM2 with E-cadherin, prevented E-cadherin degradation, and attenuated cell motility as observed by fluorescence microscopy. Thus, we provide evidence to support a novel role for MDM2 in regulating cell adhesions by a mechanism that involves degrading and down-regulating the expression of E-cadherin via an endosome pathway. This novel MDM2-regulated pathway is likely to play a biologically relevant role in cancer metastasis.

Prostate cancer is the most commonly diagnosed noncutaneous neoplasm and second most common cause of cancer-related mortality in western men. To investigate the mechanisms of prostate cancer development and progression, we did expression profiling of human prostate cancer and benign tissues. We show that the SOX4 is overexpressed in prostate tumor samples compared with benign tissues by microarray analysis, real-time PCR, and immunohistochemistry. We also show that SOX4 expression is highly correlated with Gleason score at the mRNA and protein level using tissue microarrays. Genes affected by SOX4 expression were also identified, including BCL10, CSF1, and NcoA4/ARA70. TLE-1 and BBC3/PUMA were identified as direct targets of SOX4. Silencing of SOX4 by small interfering RNA transfection induced apoptosis of prostate cancer cells, suggesting that SOX4 could be a therapeutic target for prostate cancer. Stable transfection of SOX4 into nontransformed prostate cells enabled colony formation in soft agar, suggesting that, in the proper cellular context, SOX4 can be a transforming oncogene. (Cancer Res 2006; 66(8): 4011-9)

Background We previously analyzed human embryonic kidney (HEK) cell lines for the effects that simian virus 40 (SV40) small tumor antigen (ST) has on gene expression using Affymetrix U133 GeneChips. To cross-validate and extend our initial findings, we sought to compare the expression profiles of these cell lines using an alternative microarray platform. METHODS: We have analyzed matched cell lines with and without expression of SV40 ST using an Applied Biosystems (AB) microarray platform that uses single 60-mer oligonucleotides and single-color quantitative chemiluminescence for detection. RESULTS: While we were able to previously identify only 456 genes affected by ST with the Affymetrix platform, we identified 1927 individual genes with the AB platform. Additional technical replicates increased the number of identified genes to 3478 genes and confirmed the changes in 278 (61%) of our original set of 456 genes. Among the 3200 genes newly identified as affected by SV40 ST, we confirmed 20 by QRTPCR including several components of the Wnt, Notch, and Hedgehog signaling pathways, consistent with SV40 ST activation of these developmental pathways. While inhibitors of Notch activation had no effect on cell survival, cyclopamine had a potent killing effect on cells expressing SV40 ST. CONCLUSIONS: These data show that SV40 ST expression alters cell survival pathways to sensitize cells to the killing effect of Hedgehog pathway inhibitors.