The small molecule inhibitor NAV-2729 has a complex target profile including multiple ADP-ribosylation factor regulatory proteins.

The ADP-ribosylation factor (Arf) GTPases and their regulatory proteins are implicated in cancer progression. NAV-2729 was previously identified as a specific inhibitor of Arf6 that reduced progression of uveal melanoma in an orthotopic xenograft. Here, our goal was to assess the inhibitory effects of NAV-2729 on the proliferation of additional cell types. We found NAV-2729 inhibited proliferation of multiple cell lines, but Arf6 expression did not correlate with NAV-2729 sensitivity, and knockdown of Arf6 affected neither cell viability nor sensitivity to NAV-2729. Furthermore, binding to native Arf6 was not detected; however, we determined that NAV-2729 inhibited both Arf exchange factors and Arf GTPase-activating proteins. ASAP1, a GTPase-activating protein linked to cancer progression, was further investigated. We demonstrated that NAV-2729 bound to the PH domain of ASAP1 and changed ASAP1 cellular distribution. However, ASAP1 knockdown did not fully recapitulate the cytoskeletal effects of NAV-2729 nor affect cell proliferation. Finally, our screens identified 48 other possible targets of NAV-2729. These results illustrate the complexities of defining targets of small molecules and identify NAV-2729 as a model PH domain-binding inhibitor.

Identification of hub genes and potential networks by centrality network analysis of PCR amplified Fusarium oxysporum f. sp. lycopersici EF1α gene.

BACKGROUND: Fusarium wilt is a devastating soil-borne fungal disease of tomato across the world. Conventional method of disease prevention including usage of common pesticides and methods like soil solarisation are usually ineffective in the treatment of this disease. Therefore, there is an urgent need to identify virulence related genes in the pathogen which can be targeted for fungicide development. RESULTS: Pathogenicity testing and phylogenetic classification of the pathogen used in this study confirmed it as Fusarium oxysporum f. sp. lycopersici (Fol) strain. A recent discovery indicates that EF1α, a protein with conserved structural similarity across several fungal genera, has a role in the pathogenicity of Magnaporthe oryzae, the rice blast fungus. Therefore, in this study we have done structural and functional classification of EF1α to understand its role in pathogenicity of Fol. The protein model of Fol EF1α was created using the template crystal structure of the yeast elongation factor complex EEF1A:EEF1BA which showed maximum similarity with the target protein. Using the STRING online database, the interactive information among the hub genes of EF1α was identified and the protein-protein interaction network was recognized using the Cytoscape software. On combining the results of functional analysis, MCODE, CytoNCA and CytoHubba 4 hub genes including Fol EF1α were selected for further investigation. The three interactors of Fol EF1α showed maximum similarity with homologous proteins found in Neurospora crassa complexed with the known fungicide, cycloheximide. Through the sequence similarity and PDB database analysis, homologs of Fol EF1α were found: EEF1A:EEF1BA in complex with GDPNP in yeast and EF1α in complex with GDP in Sulfolobus solfataricus. The STITCH database analysis suggested that EF1α and its other interacting partners interact with guanosine diphosphate (GDPNP) and guanosine triphosphate (GTP). CONCLUSIONS: Our study offers a framework for recognition of several hub genes network in Fusarium wilt that can be used as novel targets for fungicide development. The involvement of EF1α in nucleocytoplasmic transport pathway suggests that it plays role in GTP binding and thus apart from its use as a biomarker, it may be further exploited as an effective target for fungicide development. Since, the three other proteins that were found to be tightly associated Fol EF1α have shown maximum similarity with homologous proteins of Neurospora crassa that form complex with fungicide- Cycloheximide. Therefore, we suggest that cycloheximide can also be used against Fusarium wilt disease in tomato. The active site cavity of Fol EF1α can also be determined for computational screening of fungicides using the homologous proteins observed in yeast and Sulfolobus solfataricus. On this basis, we also suggest that the other closely associated genes that have been identified through STITCH analysis, they can also be targeted for fungicide development.

Heavy metals toxicity on epigenetic modifications in the pathogenesis of Alzheimer's disease (AD).

Alzheimer's disease (AD) is a progressive decline in cognitive ability and behavior which eventually disrupts daily activities. AD has no cure and the progression rate varies unlikely. Among various causative factors, heavy metals are reported to be a significant hazard in AD pathogenesis. Metal-induced neurodegeneration has been focused globally with thorough research to unravel the mechanistic insights in AD. Recently, heavy metals suggested to play an important role in epigenetic alterations which might provide evidential results on AD pathology. Epigenetic modifications are known to play towards novel therapeutic approaches in treating AD. Though many studies focus on epigenetics and heavy metal implications in AD, there is a lack of research on heavy metal influence on epigenetic toxicity in neurological disorders. The current review aims to elucidate the plausible role of cadmium (Cd), iron (Fe), arsenic (As), copper (Cu), and lithium (Li) metals on epigenetic factors and the increase in amyloid beta and tau phosphorylation in AD. Also, the review discusses the common methods of heavy metal detection to implicate in AD pathogenesis. Hence, from this review, we can extend the need for future research on identifying the mechanistic behavior of heavy metals on epigenetic toxicity and to develop diagnostic and therapeutic markers in AD.

Synbiotics as potent functional food: recent updates on therapeutic potential and mechanistic insight.

Synbiotics are the specific mixtures of prebiotics with probiotics intended to give health benefits to the host by stabilizing and supporting the gut microbiota.The prebiotic substance used in the synbiotics selectively favors the growth and metabolite production of probiotics. Gut microbiome dysbiosis may lead to generation and progression of various chronic diseases. Synbiotics act synergistically to modulate the gut ecosystem for improvement of metabolic health of the host. Probiotics have been found promising against various diseases being safer, effective, as an alternative or combinatorial therapy. Specific combinations of probiotics with suitable prebiotic substrate as synbiotics, may be the more effective therapeutic agents that can provide all benefits of probiotics as well as prebiotics. Though, effective combinations, dosage, mechanism of action, safety, cost effectiveness and other clinical investigations are required to be established along with other relevant aspects. Synbiotics have the potential to be functional food of importance in future. Present review summarizes the mechanistic overview of synbiotics related to gut microbiota, therapeutic potential and promising health benefits for human illnesses according to the available literature. In present scenario, synbiotics are more promising future alternatives as therapeutics to maintain healthy microbiota inside the host gut which directly affects the onset or development ofrelated disorders or diseases.

Current paradigms in epigenetic anticancer therapeutics and future challenges.

Any alteration at the genetic or epigenetic level, may result in multiplex of diseases including tumorigenesis which ultimately results in the cancer development. Restoration of the normal epigenome by reversing the epigenetic alterations have been reported in tumors paving the way for development of an effective epigenetic treatment in cancer. However, delineating various epigenetic events has been a challenging task so far despite substantial progress in understanding DNA methylation and histone modifications during transcription of genes. Many inhibitors in the form of epigenetic drugs mostly targeting chromatin and histone modifying enzymes including DNA methyltransferase (DNMT) enzyme inhibitors and a histone deacetylases (HDACs) inhibitor, have been in use subsequent to the approval by FDA for cancer treatment. Similarly, other inhibitory drugs, such as FK228, suberoylanilide hydroxamic acid (SAHA) and MS-275, have been successfully tested in clinical studies. Despite all these advancements, still we see a hazy view as far as a promising epigenetic anticancer therapy is concerned. The challenges are to have more specific and effective inhibitors with negligible side effects. Moreover, the alterations seen in tumors are not well understood for which one has to gain deeper insight into the tumor pathology as well. Current review focusses on such epigenetic alterations occurring in cancer and the effective strategies to utilize such alterations for potential therapeutic use and treatment in cancer.

Plant growth promotion and differential expression of defense genes in chilli pepper against Colletotrichum truncatum induced by Trichoderma asperellum and T. harzianum.

BACKGROUND: Trichoderma asperellum and T. harzianum were assessed in this study as a potential biological control against Colletotrichum truncatum. C. truncatum is a hemibiotrophic fungus that causes anthracnose disease in chilli thereby affecting plant growth and fruit yield. Scanning electron microscope (SEM) technique showed the beneficial interaction between chilli root-Trichoderma spp. inducing the plant growth promotion, mechanical barrier, and defense network under C. truncatum challenged conditions. METHODS: Seeds bio-primed with T. asperellum, T. harzianum, and T. asperellum + T. harzianum promoted the plant growth parameters and strengthening of physical barrier via lignification on the wall of vascular tissues. Seed primed with bioagents were used for exploring the molecular mechanism of defense response in pepper against anthracnose to assess the temporal expression of six defense genes in the Surajmukhi variety of Capsicum annuum. QRT-PCR demonstrated induction of defense responsive genes in chilli pepper bioprimed with Trichoderma spp. such as plant defensin 1.2 (CaPDF1.2), superoxide dismutase (SOD), ascorbate peroxidase (APx), guaiacol peroxidase (GPx), pathogenesis related proteins PR-2 and PR-5. RESULTS: The results showed that bioprimed seeds were assessed for T. asperellum, T. harzianum, and T. asperellum + T. harzianum-chilli root colonization interaction under in vivo conditions. The results of the scanning electron microscope revealed that T. asperellum, T. harzianum and T. asperellum + T. harzianum interact with chilli roots directly via the development of plant-Trichoderma interaction system. Seeds bio-primed with bioagents promoted the plant growth parameters, fresh and dry weight of shoot and root, plant height, leaf area index, number of leaves, stem diameter and strengthening of physical barrier via lignification on the wall of vascular tissues and expression of six defense related genes in pepper against anthracnose. CONCLUSIONS: Application of T. asperellum and T. harzianum and in combination of treatments enhanced the plant growth. Further, as seeds bioprimed with T. asperellum, T. harzianum and in combination with treatment of T. asperellum + T. harzianum induced the strengthening of the cell wall by lignification and expression of six defense related genes CaPDF1.2, SOD, APx, GPx, PR-2 and PR-5 in pepper against C. truncatum. Our study contributed for better disease management through biopriming with T. asperellum, T. harzianum and T. asperellum + T. harzianum. The biopriming possess enormous potential to promote plant growth, modulate the physical barrier, and induced the defense related genes in chilli pepper against anthracnose.

Mung bean as a potent emerging functional food having anticancer therapeutic potential: Mechanistic insight and recent updates.

Cancer is still a major challenge for humans. In recent years, researchers have focused on plant-based metabolites as a safe, efficient, alternative or combinatorial, as well as cost-effective preventive strategy against carcinogenesis. Mung bean is an important nutritious legume, and known for providing various health benefits due to various bioactive phytochemicals and easily digestible proteins. Regular intake of mung bean helps to regulate metabolism by affecting the growth and survival of good microbes in the host gut. Mung bean has also been reported to have anti-inflammatory, antioxidant, antiproliferative, and immunomodulatory properties. These properties may possess the preventive potential of mung bean against carcinogenesis. Bibliographic databases for peer-reviewed research literature were searched through a structured conceptual approach using focused review questions on mung beans, anticancer, therapeutics, and functional foods along with inclusion/exclusion criteria. For the appraisal of the quality of retrieved articles, standard tools were employed. A deductive qualitative content analysis methodology further led us to analyze outcomes of the research and review articles. The present review provides recent updates on the anticancer potential of mung bean and the possible mechanism of action thereof to prevent carcinogenesis and metastasis. Extensive research on the active metabolites and mechanisms of action is required to establish the anticancer potential of mung bean. Keeping the above facts in view, mung bean should be investigated for its bioactive compounds, to be considered as functional food of the future.

Microbiome dysbiosis in cancer: Exploring therapeutic strategies to counter the disease.

Cancer being a multiplex disease which involves many genomic and physiological alterations that occur consistently in the cancerous tissue, making the treatment and management of the disease even more complicated. The human gut microbiota (GM) harbors collective genomes of microbes comprising of trillions of bacteria along with fungi, archaea, and viruses that have the tendency to affect the development and progression of cancer. Moreover, inter-microbial interactions, diversity and distinct differences among the GM populations could influence the course of disease, making the microbiome an ideal target or to be modulated in such a way so as to improve cancer therapeutics with better efficacy and reduced toxicity. Current review focuses upon exploring the association of gut microbiota with the progression of cancer for which a structured search of bibliographic databases for peer-reviewed research literature has been carried out using focused review questions and inclusion/exclusion criteria. Through this review one could envisage a wide-spectrum role of microbiota in maintaining host metabolism, immune homeostasis paving the way for an anticancer diagnostic and therapeutic solution that has the potential to counter the menace of anti-cancer drug resistance as well.

Probiotics in microbiome ecological balance providing a therapeutic window against cancer.

The gut microbiota composition and dietary factors in our food along with the use of prebiotics and probiotics play an important role in the maintenance of human health. A well-balanced gut microbial population is necessary for the host and the microbiota to coexist in a mutually beneficial relationship maintaining homeostasis. Considering the potential of modern technological tools, it is possible nowadays to engineer prebiotic bacteria having a positive influence on the microbiome on one hand while on the other one may have the ease to get rid of the pathogenic proinflammatory microbes or elements causing dysbiosis. Past studies have seen that in cancer there is a loss of inter-microbial relationship cum interactions within microbiota members, the metabolic products produced by them and the host immune system in a microbial ecosystem, leading to dysbiosis. Current review highlights the importance of probiotics in the management of cancer by bringing together majority of the studies together at a single platform and moreover, stresses upon the need to maintain eubiosis in order to evade and inhibit the progression of cancer. Continuous expansion in knowledge about probiotics, their effect on various cancers and the underlying mechanism of action has raised the global scientific interest towards their possible use against different cancers. Furthermore, the article emphasizes upon the need to explore newer therapeutic targets comprising of the microbiome which could further pave the way to the concept of personalized medicines for various kinds of malignancies so as to derive maximum benefits of a treatment modality and to preserve the microbial homeostasis.

Multiplexed Mach-Zehnder interferometer assisted ring resonator sensor.

A Mach-Zehnder interferometer assisted ring resonator configuration (MARC)-based multiplexed photonic sensor with a large measurement range is experimentally demonstrated. The presented MARC sensor consists of a balanced Mach-Zehnder interferometer and a ring resonator acting as a sensing component. It produces transmission responses with unique spectral signatures, which depend on the physical angular separation between the through port and the drop port waveguides. These unique spectral signatures enhance the effective free spectral range of ring resonators. Hence MARC sensors with a large measurement range are realized. We experimentally demonstrated that the measurement range from the MARC with 135° angular separation is 8x larger than a standard ring resonator. Moreover, by utilizing the MARC, we distinguished the responses from two and three ring resonators multiplexed together. These results verify proof-of-principle for the MARC-based sensors. This inexpensive compact multipurpose device holds promise for numerous applications.

Multifaceted antiviral therapeutic potential of dietary flavonoids: Emerging trends and future perspectives.

Phytochemicals are the natural biomolecules produced by plants via primary or secondary metabolism, which have been known to have many potential health benefits to human beings. Flavonoids or phytoestrogens constitute a major group of such phytochemicals widely available in variety of vegetables, fruits, herbs, tea, and so forth, implicated in a variety of bio-pharmacological and biochemical activities against diseases including bacterial, viral, cancer, inflammatory, and autoimmune disorders. More recently, these natural biomolecules have been shown to have effective antiviral properties via therapeutically active ingredients within them, acting at different stages of infection. Current review emphasizes upon the role of these flavonoids in physiological functions, prevention and treatment of viral diseases. More so the review focuses specifically upon the antiviral effects exhibited by these natural biomolecules against RNA viruses including coronaviruses. Furthermore, the article would certainly provide a lead to the scientific community for the effective therapeutic antiviral use of flavonoids using potential cost-effective tools for improvement of the pharmacokinetics, bioavailability, and biodistribution of such compounds for the concrete action along with the promotion of human health.

Spectral shaping of ring resonator transmission response.

We present a Mach-Zehnder interferometer assisted ring resonator configuration (MARC) to realize resonator transmission spectra with unique spectral signatures and significantly large effective free spectral ranges. Transmission spectra with unique spectral signatures are generated by changing the angular separation between the through port and the drop port waveguides of the ring resonator (RR). These spectral signatures are comprised of several distinct resonance lineshapes including Lorentzian, inverse Lorentzian and asymmetric Fano-like shapes. One of the spectral signatures generated from the MARC device is utilized for the temperature sensing measurement to demonstrate a MARC-based sensor with high Q-factor and wide measurement range.

An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer.

BACKGROUND: Before the approval of first-line immune checkpoint inhibitors, platinum doublets were the standard of care in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. Pemetrexed-platinum combinations are preferred in non-squamous NSCLC. However, there has been no direct comparison to paclitaxel-carboplatin. METHODS: This open-label randomized trial was designed to compare pemetrexed-carboplatin with (weekly) paclitaxel-carboplatin in treatment-naïve advanced/metastatic non-squamous NSCLC without driver mutations. Patients received either pemetrexed 500 mg/m2 and carboplatin AUC 5 every 3 weeks, or paclitaxel 80 mg/m2 on day 1, day 8, and day 15 with carboplatin AUC 5 every 4 weeks for 4 cycles. Patients in both arms were allowed to receive pemetrexed maintenance. RESULTS: A total of 180 patients were enrolled. The study was terminated early; however, at the time of analysis 75.8% of the required events had occurred. Finally, 164 patients were evaluable, 83 in the pemetrexed arm and 81 in the paclitaxel arm. After a median follow-up of 17 months, progression-free survival (PFS) rates at 6 months were not different in the two treatment arms (47.45 vs. 48.64%, p = 0.88). The median PFS values were 5.67 months (95% CI 3.73-7.3) and 5.03 months (95% CI 2.63-7.43) in each arm, respectively (HR 1.13, 95% CI 0.81-1.59, p = 0.44). The median overall survival was also not different: 14.83 months (95% CI 9.5-18.73) and 11.3 (95% CI 8.3-19.7; HR 1.19, 95% CI 0.8-1.78, p = 0.37). All grade toxicities were similar except for alopecia and peripheral neuropathy, which were higher in the paclitaxel arm. CONCLUSION: Pemetrexed-carboplatin is not superior to (weekly) paclitaxel-carboplatin as the first-line regimen in advanced non-squamous NSCLC in terms of PFS.

Amalgamation of Solid Dispersion and Melt Adsorption Technique: Improved In Vitro and In Vivo Performance of Ticagrelor Tablets.

Ticagrelor (TG) suffers from low peroral bioabsorption (36%) due to P-gp efflux and poor solubility (10 µg/mL). TG solid dispersion adsorbates (TG-SDAs) were formulated using an amalgamation of solid dispersion and melt adsorption techniques which were simple, economic, scalable, and solvent-free. FTIR indicated no incompatibility between drug and excipients. DSC, XRD, and SEM suggested a reduction in TG crystallinity. Q30min from TG-SUSP and TG-conventional tablets was only 2.30% and 6.59% respectively whereas TG-SDA-based tablets exhibited a significantly higher drug release of 86.47%. Caco-2 permeability studies showed 3.83-fold higher permeability of TG from TG-SDAs. TG-SDA-based tablets exhibited relative bioavailability of 748.53% and 153.43% compared to TG-SUSP and TG-conventional tablets respectively in rats. TG-SDA-based tablets were devoid of any cytotoxicity as indicated by MTT assay and exhibited better antiplatelet activity in rats. Enhanced oral bioavailability of TG-SDAs can be attributed to inhibition of P-gp efflux by PEG 4000, increased wettability, and reduced crystallinity of drug leading to improved drug solubility and dissolution. Improved bioabsorption results in a reduction of dose, cost of therapy as well as dose-related side effects. Thus, SDAs can be considered a promising and scalable approach for the improvement of dissolution rate and solubility of TG. TG-SDAs can be translated to an effective and safe dosage form, whereby its rapid onset of action promotes the prevention of heart attack, stroke, and related ill events in individuals with the acute coronary syndrome. However, scale-up, validation, and clinical-studies are necessary for confirmation of the proof-of-concept.

Waveguide asymmetric long-period grating couplers as refractive index sensors.

A highly sensitive integrated photonic transducer is designed by utilizing asymmetric long-period gratings on a silicon waveguide. These gratings are formed by periodic perturbation of the waveguide width, leading to coupling between the fundamental mode and the 1st order asymmetric leaky mode. The coupled modes are studied via finite-element and finite-difference time-domain methods. Only a single fabrication step is required to realize this novel design. The device is utilized as a refractive index sensor in liquid, yielding a sensitivity of 5078 nm/RIU. The design is a unique combination of being highly sensitive, easily fabricated and highly compact.

Inorganic clay nanocomposite system for improved cholinesterase inhibition and brain pharmacokinetics of donepezil.

Objective: Brain drug delivery for effective treatment of neurodegenerative disorders is limited due to the selective permeability of blood brain barrier (BBB). During the past few years, development of novel delivery system has attracted considerable attention of formulation scientists to overcome the permeability limitation caused by BBB.Significance: Based on the outcomes of this study and taking into consideration of the unique characteristics of laponite, it can be further explored to deliver many other central nervous system acting drugs.Methods: In the present study, laponite (LAP) nanocomposites were exploited for the improved brain delivery of donepezil (DZ) following encapsulation approach due to their nano-size and positive charge at pH <9.Result: The size of prepared nanocomposites was 53.7 ± 4.0 to 137.7 ± 11.0 nm. The drug was released in a sustained manner till 120 h in phosphate buffer saline (pH 7.4) and acid phthalate buffer (pH 4.0). LAPDZ formulations inhibited acetylcholinesterase approximately by 82%, significantly higher (p < 0.05) than plain DZ (30%). Swiss albino mice exhibited enhanced brain uptake of LAPDZ administered via intravenous route. Promising pharmacokinetic parameters were observed in animals treated with LAPDZ. LAPDZ formulation showed half-life (t1/2), volume of distribution (Vd) and clearance (Cl) as 5.53 ± 0.40 h-1, 0.129 ± 0.02 L, 0.015 ± 0.002 L/h, respectively. While DZ solution showed the same parameters as 1.06 ± 0.12 h-1, 0.168 ± 0.01 L, 0.106 ± 0.013 L/h, respectively. The brain uptake of LAPDZ formulation was improved with quintuplet t1/2.Conclusion: Based on the results of present study, it is proposed that the formulated nanocomposite would result in improved patient compliance with therapeutic effect at lower doses.

Ultrasonographic assessment of airway.

Ultrasound is gaining increasing popularity among anesthesiologists as it is readily available and provides real-time imaging for various procedures. It is considered as a "visual stethoscope" of the anesthesiologist. After establishing its use in regional blocks and central venous catheter insertion, it is now finding increasing use in anticipation of difficult airway and securing and maintaining it. It has challenged the classical approach of clinical assessment of airway and allows more dynamic bedside assessment. This article attempts to briefly outline the role of ultrasound and its applications for airway management in patients.

Non-bronchial causes of haemoptysis: imaging and interventions.

PURPOSE: To describe non-bronchial causes of haemoptysis on imaging and the role of interventional radiology in their management from cases of haemoptysis archived from our database at a tertiary care, federally funded institution. MATERIAL AND METHODS: Retrospective analysis of cases that presented with haemoptysis in our institution from 2008 to 2013 was done, and details of cases in which the bleeding was from a non-bronchial source were archived and details of imaging and treatment were recorded. RESULTS: Retrospective analysis of patients presenting with haemoptysis yielded 24 (n = 24) patients having haemoptysis from non-bronchial sources. Causes of haemoptysis were: Rasmussen aneurysms (n = 12/24), costocervical trunk pseudoaneurysm (n = 1/24), left internal mammillary artery pseudoaneurysm (n = 1/24), left ventricular aneurysms (n = 3/24), pulmonary arteriovenous malformations (AVMs) (n = 5/24), and proximal interruption of pulmonary artery (n = 2/24). Imaging and interventional radiology management are described in detail. CONCLUSIONS: Haemoptysis can be from non-bronchial sources, which may be either from systemic or pulmonary arteries or cardio-pulmonary fistulas. Bronchial computed tomography angiography (CTBA), if feasible, must always be considered before bronchial artery embolisation because it precisely identifies the source of haemorrhage and vascular anatomy that helps the interventional radiologist in pre-procedural planning. This circumvents chances of re-bleed if standard bronchial artery embolisation is done without CTBA.

A Nexus model of cellular transition in cancer.

The exact cause of cancer is one of the most immutable medical questions of the century. Cancer as an evolutionary disease must have a purpose and understanding the purpose is more important than decoding the cause. The model of cancer proposed herein, provides a link between the cellular biochemistry and cellular genetics of cancer evolution. We thus call this model as the "Nexus model" of cancer. The Nexus model is an effort to identify the most apparent route to the disease. We have tried to utilize existing cancer literature to identify the most plausible causes of cellular transition in cancer, where the primary cancer-causing agents (physical, chemical or biological) act as inducing factors to produce cellular impeders. These cellular impeders are further linked to the Nexus. The Nexus then generates codes for epigenetics and genetics in cancer development.

CST, an Herbal Formula, Exerts Anti-Obesity Effects through Brain-Gut-Adipose Tissue Axis Modulation in High-Fat Diet Fed Mice.

The brain, gut, and adipose tissue interact to control metabolic pathways, and impairment in the brain-gut-adipose axis can lead to metabolic disorders, including obesity. Chowiseungcheng-tang (CST), a herbal formulation, is frequently used to treat metabolic disorders. Here, we investigated the anti-obesity effect of CST and its link with brain-gut-adipose axis using C57BL/6J mice as a model. The animals were provided with a normal research diet (NRD) or high-fat diet (HFD) in absence or presence of CST or orlistat (ORL) for 12 weeks. CST had a significant anti-obesity effect on a number of vital metabolic and obesity-related parameters in HFD-fed mice. CST significantly decreased the expression levels of genes encoding obesity-promoting neuropeptides (agouti-related peptide, neuropeptide Y), and increased the mRNA levels of obesity-suppressing neuropeptides (proopiomelanocortin, cocaine-and amphetamine-regulated transcript) in the hypothalamus. CST also effectively decreased the expression level of gene encoding obesity-promoting adipokine (retinol-binding protein-4) and increased the mRNA level of obesity-suppressing adipokine (adiponectin) in visceral adipose tissue (VAT). Additionally, CST altered the gut microbial composition in HFD groups, a phenomenon strongly associated with key metabolic parameters, neuropeptides, and adipokines. Our findings reveal that the anti-obesity impact of CST is mediated through modulation of metabolism-related neuropeptides, adipokines, and gut microbial composition.