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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.

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: 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.

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.

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.

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.

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.

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 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.

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.

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)