Alleviation of neuropathic pain with neuropeptide Y requires spinal Npy1r interneurons that coexpress Grp.

Neuropeptide Y targets the Y1 receptor (Y1) in the spinal dorsal horn (DH) to produce endogenous and exogenous analgesia. DH interneurons that express Y1 (Y1-INs; encoded by Npy1r) are necessary and sufficient for neuropathic hypersensitivity after peripheral nerve injury. However, as Y1-INs are heterogenous in composition in terms of morphology, neurophysiological characteristics, and gene expression, we hypothesized that a more precisely defined subpopulation mediates neuropathic hypersensitivity. Using fluorescence in situ hybridization, we found that Y1-INs segregate into 3 largely nonoverlapping subpopulations defined by the coexpression of Npy1r with gastrin-releasing peptide (Grp/Npy1r), neuropeptide FF (Npff/Npy1r), and cholecystokinin (Cck/Npy1r) in the superficial DH of mice, nonhuman primates, and humans. Next, we analyzed the functional significance of Grp/Npy1r, Npff/Npy1r, and Cck/Npy1r INs to neuropathic pain using a mouse model of peripheral nerve injury. We found that chemogenetic inhibition of Npff/Npy1r-INs did not change the behavioral signs of neuropathic pain. Further, inhibition of Y1-INs with an intrathecal Y1 agonist, [Leu31, Pro34]-NPY, reduced neuropathic hypersensitivity in mice with conditional deletion of Npy1r from CCK-INs and NPFF-INs but not from GRP-INs. We conclude that Grp/Npy1r-INs are conserved in higher order mammalian species and represent a promising and precise pharmacotherapeutic target for the treatment of neuropathic pain.

Vibrio gazogenes-dependent disruption of aflatoxin biosynthesis in Aspergillus flavus: the connection with endosomal uptake and hyphal morphogenesis.

Aflatoxins, a family of fungal secondary metabolites, are toxic and carcinogenic compounds that pose an enormous threat to global food safety and agricultural sustainability. Specifically agricultural products in African, Southeast Asian and hot and humid regions of American countries suffer most damage from aflatoxin producing molds due to the ideal climate conditions promoting their growth. Our recent studies suggest that Vibrio gazogenes (Vg), an estuarine bacterium non-pathogenic to plants and humans, can significantly inhibit aflatoxin biosynthesis in the producers. In this study, we investigated the mechanism underlying Vg-dependent aflatoxin inhibition using the prominent aflatoxin producer, Aspergillus flavus. We show that aflatoxin inhibition upon Vg treatment was associated with fungal uptake of Vg-prodigiosin, a red pigment, which was consistently visible inside fungal hyphae during treatment. The association of prodigiosin with aflatoxin inhibition was further evident as Serratia marcescens, another prodigiosin producer, significantly inhibited aflatoxin, while non-producers like Escherichia coli, Staphylococcus aureus, Vibrio harveyi, and Vibrio fischeri did not. Also, pure prodigiosin significantly inhibited aflatoxin biosynthesis. Endocytosis inhibitors, filipin and natamycin, reduced the Vg-prodigiosin uptake by the fungus leading to a significant increase in aflatoxin production, suggesting that uptake is endocytosis-dependent. The Vg treatment also reduced hyphal fusion (>98% inhibition) and branching, which are both endosome-dependent processes. Our results, therefore, collectively support our theory that Vg-associated aflatoxin inhibition is mediated by an endocytosis-dependent uptake of Vg-prodigiosin, which possibly leads to a disruption of normal endosomal functions.

NLR family pyrin domain containing 3 (NLRP3) inflammasomes and peripheral neuropathic pain - Emphasis on microRNAs (miRNAs) as important regulators.

Neuropathic pain is caused by the lesion or disease of the somatosensory system and can be initiated and/or maintained by both central and peripheral mechanisms. Nerve injury leads to neuronal damage and apoptosis associated with the release of an array of pathogen- or damage-associated molecular patterns to activate inflammasomes. The activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome contributes to neuropathic pain and may represent a novel target for pain therapeutic development. In the current review, we provide an up-to-date summary of the recent findings on the involvement of NLRP3 inflammasome in modulating neuropathic pain development and maintenance, focusing on peripheral neuropathic conditions. Here we provide a detailed review of the mechanisms whereby NLRP3 inflammasomes contribute to neuropathic pain via (1) neuroinflammation, (2) apoptosis, (3) pyroptosis, (4) proinflammatory cytokine release, (5) mitochondrial dysfunction, and (6) oxidative stress. We then present the current research literature reporting on the antinociceptive effects of several natural products and pharmacological interventions that target activation, expression, and/or regulation of NLRP3 inflammasome. Furthermore, we emphasize the effects of microRNAs as another regulator of NLRP3 inflammasome. In conclusion, we summarize the possible caveats and future perspectives that might provide successful therapeutic approaches against NLRP3 inflammasome for treating or preventing neuropathic pain conditions.

Autism and associated disorders: cannabis as a potential therapy.

Autism spectrum disorder (ASD) is a group of disabilities with impairments in physical, verbal, and behavior areas. Regardless the growing frequency of autism, no medicine has been formed for the management of the ASD primary symptoms. The most frequently prescribed drugs are off-label. Therefore, there is necessity for an advance tactic for the treatment of autism. The endocannabinoid system has a central role in ruling emotion and social behaviors. Dysfunctions of the system donate to the behavioral deficits in autism. Therefore, the endocannabinoid system represents a potential target for the development of a novel autism therapy. Cannabis and associated compounds have produced substantial research attention as a capable therapy in neurobehavioral and neurological syndromes. In this review we examine the potential benefits of medical cannabis and related compounds in the treatment of ASD and concurrent disorders.

Surveillance of SARS-CoV-2 RNA in open-water sewage canals contaminated with untreated wastewater in resource-constrained regions.

Sewage-based surveillance for COVID-19 has been described in multiple countries and multiple settings. However, nearly all are based on testing sewage treatment plant inflows and outflows using structured sewage networks and treatment systems. Many resource-limited countries worldwide have open canals, lakes and other such waste-contaminated water bodies that act as a means of sewage effluent discharge. These could serve as hyperlocal testing points for detecting COVID-19 incidence using the effluents from nearby communities. However, a sensitive, robust and economical method of SARS-CoV-2 RNA detection from open waste contaminated water bodies in resource-constrained regions is currently lacking. A protocol employed in Bangalore, India, where SARS-CoV-2 RNA levels were evaluated using two open canal systems during the first and second waves in the present study. SARS-CoV-2 RNA was measured using two strategies: a modified TrueNATTM microchip-based rapid method and traditional real-time reverse transcription-PCR (rRT-PCR), which were compared for analytical sensitivity, cost and relative ease of use. SARS-CoV-2 RNA levels were detected at lower levels during the earlier half compared to the later half of the first wave in 2020. The opposite trend was seen in the second wave in 2021. Interestingly, the change in RNA levels corresponded with the community burden of COVID-19 at both sites. The modified TrueNATTM method yielded concordant results to traditional rRT-PCR in sensitivity and specificity and cost. It provides a simple, cost-effective method for detecting and estimating SARS-CoV-2 viral RNA from open-water sewage canals contaminated with human excreta and industrial waste that can be adopted in regions or countries that lack structured sewage systems.

The Effects of Nuclear Factor Erythroid 2 (NFE2)-Related Factor 2 (Nrf2) Activation in Preclinical Models of Peripheral Neuropathic Pain.

Oxidative stress, resulting from an imbalance between the formation of damaging free radicals and availability of protective antioxidants, can contribute to peripheral neuropathic pain conditions. Reactive oxygen and nitrogen species, as well as products of the mitochondrial metabolism such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, are common free radicals. Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) is a transcription factor encoded by the NFE2L2 gene and is a member of the cap 'n' collar subfamily of basic region leucine zipper transcription factors. Under normal physiological conditions, Nrf2 remains bound to Kelch-like ECH-associated protein 1 in the cytoplasm that ultimately leads to proteasomal degradation. During peripheral neuropathy, Nrf2 can translocate to the nucleus, where it heterodimerizes with muscle aponeurosis fibromatosis proteins and binds to antioxidant response elements (AREs). It is becoming increasingly clear that the Nrf2 interaction with ARE leads to the transcription of several antioxidative enzymes that can ameliorate neuropathy and neuropathic pain in rodent models. Current evidence indicates that the antinociceptive effects of Nrf2 occur via reducing oxidative stress, neuroinflammation, and mitochondrial dysfunction. Here, we will summarize the preclinical evidence supporting the role of Nrf2 signaling pathways and Nrf2 inducers in alleviating peripheral neuropathic pain.

Increased prevalence of indoor Aspergillus and Penicillium species is associated with indoor flooding and coastal proximity: a case study of 28 moldy buildings.

Indoor flooding is a leading contributor to indoor dampness and the associated mold infestations in the coastal United States. Whether the prevalent mold genera that infest the coastal flood-prone buildings are different from those not flood-prone is unknown. In the current case study of 28 mold-infested buildings across the U.S. east coast, we surprisingly noted a trend of higher prevalence of indoor Aspergillus and Penicillium genera (denoted here as Asp-Pen) in buildings with previous flooding history. Hence, we sought to determine the possibility of a potential statistically significant association between indoor Asp-Pen prevalence and three building-related variables: (i) indoor flooding history, (ii) geographical location, and (iii) the building's use (residential versus non-residential). Culturable spores and hyphal fragments in indoor air were collected using the settle-plate method, and corresponding genera were confirmed using phylogenetic analysis of their ITS sequence (the fungal barcode). Analysis of variance (ANOVA) using Generalized linear model procedure (GLM) showed that Asp-Pen prevalence is significantly associated with indoor flooding as well as coastal proximity. To address the small sample size, a multivariate decision tree analysis was conducted, which ranked indoor flooding history as the strongest determinant of Asp-Pen prevalence, followed by geographical location and the building's use.

Sex Differences in Protein Kinase A Signaling of the Latent Postoperative Pain Sensitization That Is Masked by Kappa Opioid Receptors in the Spinal Cord.

Latent sensitization (LS) of pain engages pronociceptive signaling pathways in the dorsal horn that include NMDA receptor (NMDAR)→adenylyl cyclase-1 (AC1)→protein kinase A (PKA), and exchange proteins directly activated by cyclic AMP (Epacs). To determine whether these pathways operate similarly between males and females or are under the inhibitory control of spinal κ opioid receptors (KOR), we allowed hyperalgesia to resolve after plantar incision and then blocked KOR with intrathecal administration of LY2456302, which reinstated hyperalgesia and facilitated touch-evoked immunoreactivity of phosphorylated extracellular signal-regulated kinase (pERK) in neurons (NeuN) but not astrocytes (GFAPs) nor microglia (Iba1). LY2456302 reinstated hyperalgesia even when administered 13 months later, indicating that chronic postoperative pain vulnerability persists for over a year in a latent state of remission. In both sexes, intrathecal MK-801 (an NMDAR competitive antagonist) prevented LY2456302-evoked reinstatement of hyperalgesia as did AC1 gene deletion or the AC1 inhibitor NB001. NB001 also prevented stimulus-evoked pERK. In both sexes, the Epac inhibitor ESI-09 prevented reinstatement, whereas the Epac activator 8-CPT reinstated hyperalgesia. By contrast, the PKA inhibitor H89 prevented reinstatement only in male mice, whereas the PKA activator 6-bnz-cAMP itself evoked reinstatement at all doses tested (3-30 nmol, i.t.). In neither sex did incision change gene expression of KOR, GluN1, PKA, or Epac1 in dorsal horn. We conclude that sustained KOR signaling inhibits spinal PKA-dependent mechanisms that drive postoperative LS in a sex-dependent manner. Our findings support the development of AC1, PKA, and Epac inhibitors toward a new pharmacotherapy for chronic postoperative pain.SIGNIFICANCE STATEMENT Because of neural mechanisms that are not well understood, men and women respond differently to treatments for chronic pain. We report that surgical incision recruits a pronociceptive latent pain sensitization that persisted for over a year and was kept in check by the sustained analgesic activity of κ opioid receptors. NMDAR→AC1→cAMP→Epac signaling pathways in the dorsal horn of the spinal cord maintain latent sensitization in both males and females; however, only males recruit a PKA-dependent mechanism. This work presents a novel male-specific mechanism for the promotion of chronic postoperative pain.

Structural and biological aspects of natural bridged macrobicyclic peptides from marine resources.

Among peptide-based drugs, naturally occurring bicyclic compounds have been established as molecules with unique therapeutic potential. The diverse pharmacological activities associated with bicyclic peptides from marine tunicates, sponges, and bacteria render them suitable to be employed as effective surrogate between complex and small therapeutic moieties. Bicyclic peptides possess greater conformational rigidity and higher metabolic stability as compared with linear and monocyclic peptides. The antibody-like affinity and specificity of bicyclic peptides enable their binding to the challenging drug targets. Bridged macrobicyclic peptides from natural marine resources represent an underexplored class of molecules that provides promising platforms for drug development owing to their biocompatibility, similarity, and chemical diversity to proteins. The present review explores major marine-derived bicyclic peptides including disulfide-bridged, histidinotyrosine-bridged, or histidinoalanine-bridged macrobicyclic peptides along with their structural characteristics, synthesis, structure-activity relationship, and bioproperties.The comparison of these macrobicyclic congeners with linear/monocyclic peptides along with their therapeutic potential are also briefly discussed.

Effects of Curcumin and Its Different Formulations in Preclinical and Clinical Studies of Peripheral Neuropathic and Postoperative Pain: A Comprehensive Review.

Lesion or disease of the somatosensory system leads to the development of neuropathic pain. Peripheral neuropathic pain encompasses damage or injury of the peripheral nervous system. On the other hand, 10-15% of individuals suffer from acute postoperative pain followed by persistent pain after undergoing surgeries. Antidepressants, anticonvulsants, baclofen, and clonidine are used to treat peripheral neuropathy, whereas opioids are used to treat postoperative pain. The negative effects associated with these drugs emphasize the search for alternative therapeutics with better efficacy and fewer side effects. Curcumin, a polyphenol isolated from the roots of Curcuma longa, possesses antibacterial, antioxidant, and anti-inflammatory properties. Furthermore, the low bioavailability and fast metabolism of curcumin have led to the advent of various curcumin formulations. The present review provides a comprehensive analysis on the effects of curcumin and its formulations in preclinical and clinical studies of neuropathic and postoperative pain. Based on the positive outcomes from both preclinical and clinical studies, curcumin holds the promise of mitigating or preventing neuropathic and postoperative pain conditions. However, more clinical studies with improved curcumin formulations are required to involve its use as adjuvant to neuropathic and postoperative drugs.

Global health research partnerships in the context of the Sustainable Development Goals (SDGs).

This themed issue on global health research has come at an opportune time in the middle of the ongoing global public health crisis arising from the coronavirus disease (COVID-19) pandemic which has claimed nearly 756,000 lives in 210 countries and territories around the world as of August 15, 2020. The public health crisis underscores the importance of global health research partnerships and collaborations to develop and evaluate the requisite health technologies to assist in containing COVID-19, other diseases, and health-related concerns that defy national borders. The 17 Sustainable Development Goals (SDGs), adopted by the member countries of the United Nations in September 2015, provide a framework for global development efforts including global health research. SDG3, which promotes health and well-being for the world populations across the age spectrum, highlights disease areas for special focus which can be adapted in specific global health research programs to serve local health needs. SDG17 promotes partnerships between high income (HIC) and low and middle-income countries (LMIC) for sustainable and equitable global development. However, given the wide disparities in fiscal and overall capacity for research between researchers in HIC and their counterparts in LMIC as well as the greater vulnerabilities of the LMIC communities when serving as research locations, a spotlight on the nature of such global health research partnerships in the context of the SDGs is desirable. This is to ensure that they are meaningful and mutually-beneficial partnerships which address local health concerns and promote long-term value for the communities involved. The objective of this commentary is, therefore, to provide a brief overview of the SDGs by way of context; explore the power differences at play when researchers from HIC are seeking research opportunities in LMIC; examine the social determinants of health and the disproportionate burden of global diseases carried by populations in LMIC to establish their vulnerability; discuss global research partnerships; and attempt to make a case for why community-based participatory research may be the preferred type of global health research partnership in the context of the SDGs.

In Vitro and In Vivo Effects of Flavonoids on Peripheral Neuropathic Pain.

Neuropathic pain is a common symptom and is associated with an impaired quality of life. It is caused by the lesion or disease of the somatosensory system. Neuropathic pain syndromes can be subdivided into two categories: central and peripheral neuropathic pain. The present review highlights the peripheral neuropathic models, including spared nerve injury, spinal nerve ligation, partial sciatic nerve injury, diabetes-induced neuropathy, chemotherapy-induced neuropathy, chronic constriction injury, and related conditions. The drugs which are currently used to attenuate peripheral neuropathy, such as antidepressants, anticonvulsants, baclofen, and clonidine, are associated with adverse side effects. These negative side effects necessitate the investigation of alternative therapeutics for treating neuropathic pain conditions. Flavonoids have been reported to alleviate neuropathic pain in murine models. The present review elucidates that several flavonoids attenuate different peripheral neuropathic pain conditions at behavioral, electrophysiological, biochemical and molecular biological levels in different murine models. Therefore, the flavonoids hold future promise and can be effectively used in treating or mitigating peripheral neuropathic conditions. Thus, future studies should focus on the structure-activity relationships among different categories of flavonoids and develop therapeutic products that enhance their antineuropathic effects.

Estrogenic, Antiestrogenic and Antiproliferative Activities of Euphorbia bicolor (Euphorbiaceae) Latex Extracts and Its Phytochemicals.

Estrogen receptor antagonists are effective in breast cancer treatment. However, the side effects of these treatments have led to a rise in searching for alternative therapies. The present study evaluated the estrogenic, antiestrogenic, and antiproliferative activities of Euphorbia bicolor (Euphorbiaceae), a plant native to south-central USA. Estrogenic and antiestrogenic activities of latex extract and its phytochemicals were evaluated with a steroid-regulated yeast system expressing the human estrogen receptor α and antiproliferative properties were assessed in the ER-positive MCF-7 and T47-D and triple-negative MDA-MB-231 and MDA-MB-469 breast carcinomas. Genistein and coumestrol identified in the latex extract induced higher estrogenic and antiestrogenic activities compared to diterpenes and flavonoids. The latex extract, resiniferatoxin (RTX) and rutin induced antiproliferative activities in all cell lines in a dose-dependent manner, but not in human normal primary dermal fibroblast cultures. A biphasic effect was observed with MDA-MB-468 breast carcinoma in which the latex extract at low concentrations increased and at high concentrations decreased cell proliferation. Treatments with latex extract in combination with RTX or rutin reduced even more the proliferation of MCF-7 breast carcinoma compared to the individual latex, RTX, and rutin treatments. E. bicolor latex phytochemicals could contribute to developing commercial therapeutic agents for breast cancer treatment.

Euphorbia bicolor (Euphorbiaceae) Latex Extract Reduces Inflammatory Cytokines and Oxidative Stress in a Rat Model of Orofacial Pain.

Recent studies have reported that the transient receptor potential V1 ion channel (TRPV1), a pain generator on sensory neurons, is activated and potentiated by NADPH oxidase-generated reactive oxygen species (ROS). ROS are increased by advanced oxidation protein products (AOPPs), which activate NADPH oxidase by upregulating Nox4 expression. Our previous studies reported that Euphorbia bicolor (Euphorbiaceae) latex extract induced peripheral analgesia, partly via TRPV1, in hindpaw-inflamed male and female rats. The present study reports that E. bicolor latex extract also can evoke analgesia via reduction of oxidative stress biomarkers and proinflammatory cytokines/chemokines in a rat model of orofacial pain. Male and female rats were injected with complete Freund's adjuvant (CFA) into the left vibrissal pad to induce orofacial inflammation, and mechanical allodynia was measured by the von Frey method. Twenty-four hours later, rats received one injection of E. bicolor latex extract or vehicle into the inflamed vibrissal pad. Mechanical sensitivity was reassessed at 1, 6, 24, and/or 72 hours. Trigeminal ganglia and trunk blood were collected at each time point. In the trigeminal ganglia, ROS were quantified using 2',7'-dichlorodihydrofluorescein diacetate dye, Nox4 protein was quantified by Western blots, and cytokines/chemokines were quantified using a cytokine array. AOPPs were quantified in trunk blood using a spectrophotometric assay. E. bicolor latex extract significantly reduced orofacial mechanical allodynia in male and female rats at 24 and 72 hours, respectively. ROS, Nox4, and proinflammatory cytokines/chemokines were significantly reduced in the trigeminal ganglia, and plasma AOPP was significantly reduced in the trunk blood of extract-treated compared to vehicle-treated rats. In vitro assays indicate that E. bicolor latex extract possessed antioxidant activities by scavenging free radicals. Together our data indicate that the phytochemicals in E. bicolor latex may serve as novel therapeutics for treating oxidative stress-induced pain conditions.

Euphorbia bicolor (Euphorbiaceae) Latex Phytochemicals Induce Long-Lasting Non-Opioid Peripheral Analgesia in a Rat Model of Inflammatory Pain.

The negative side effects of opioid-based narcotics underscore the search for alternative non-opioid bioactive compounds that act on the peripheral nervous system to avoid central nervous system-mediated side effects. The transient receptor potential V1 ion channel (TRPV1) is a peripheral pain generator activated and sensitized by heat, capsaicin, and a variety of endogenous ligands. TRPV1 contributes to peripheral sensitization and hyperalgesia, in part, via triggering the release of proinflammatory peptides, such as calcitonin gene-related peptide (CGRP), both locally and at the dorsal horn of the spinal cord. Ultrapotent exogenous TRPV1 agonists, such as resiniferatoxin identified in the latex of the exotic Euphorbia resinifera, trigger hyperalgesia followed by long lasting, peripheral analgesia. The present study reports on the analgesic properties of Euphorbia bicolor, a relative of E. resinifera, native to the Southern United States. The study hypothesized that E. bicolor latex extract induces long-lasting, non-opioid peripheral analgesia in a rat model of inflammatory pain. Both inflamed and non-inflamed adult male and female rats were injected with the methanolic extract of E. bicolor latex into the hindpaw and changes in pain behaviors were reassessed at various time points up to 4 weeks. Primary sensory neuron cultures also were treated with the latex extract or vehicle for 15 min followed by stimulation with the TRPV1 agonist capsaicin. Results showed that E. bicolor latex extract evoked significant pain behaviors in both male and female rats at 20 min post-injection and lasting around 1-2 h. At 6 h post-injection, analgesia was observed in male rats that lasted up to 4 weeks, whereas in females the onset of analgesia was delayed to 72 h post-injection. In sensory neurons, latex extract significantly reduced capsaicin-evoked CGRP release. Blocking TRPV1, but not opioid receptors, attenuated the onset of analgesia and capsaicin-induced CGRP release. Latex was analyzed by mass spectrometry and eleven candidate compounds were identified and reported here. These findings indicate that phytochemicals in the E. bicolor latex induce hyperalgesia followed by peripheral, non-opioid analgesia in both male and female rats, which occurs in part via TRPV1 and may provide novel, non-opioid peripheral analgesics that warrant further examination.

Phytoestrogens and breast cancer: In vitro anticancer activities of isoflavones, lignans, coumestans, stilbenes and their analogs and derivatives.

Breast cancer is one of the leading causes of cancer-related morbidity and mortality among women worldwide. Phytoestrogens, plant-derived polyphenols that structurally and functionally mimic 17ß-estradiol, the mammalian estrogen hormone, are known to modulate multiple molecular targets in breast cancer cells. The structural and chemical similarities to estradiol enable phytoestrogens to exert estrogenic or antiestrogenic activities by binding to the estrogen receptors. Although phytoestrogens have low affinity for estrogen receptors, they are able to compete with 17ß-estradiol for the ligand-binding domain of the receptors. Phytoestrogens trigger epigenomic effects that could be beneficial in breast cancer prevention and/or treatment. Few studies have focused on the cytotoxic and structure-activity relationships of phytoestrogen analogs and derivatives with more effective anticancer properties than their corresponding parent compounds. Phytoestrogens and their analogs and derivatives bind to estrogen receptors, with a preferential affinity for ERß, and inhibit the growth promoting activity of ERα. These bioactive compounds also exert growth inhibitory effects through various cell signaling pathways. At the level of cell cycle, they inhibit the expression of oncogenic cyclin D1, increase the expression of cyclin-dependent kinase inhibitors (p21, p27, and p57) and tumor suppressor genes (APC, ATM, PTEN, SERPINB5). Phytoestrogens and their analogs and derivatives mediate their effects on breast cancer by inhibiting estrogen synthesis and metabolism, as well as exerting antiangiogenic, antimetastatic, and epigenetic effects. Furthermore, these bioactive compounds reverse multi-drug resistance. This review offers a comprehensive summary of current literature and future perspectives on the in vitro molecular mechanisms of the anticancer activities of phytoestrogens and their analogs and derivatives on breast cancer.

In vitro Antioxidant Activities and Polyphenol Contents of Seven Commercially Available Fruits.

BACKGROUND: Fruits are considered one of the richest sources of natural antioxidants. Their consumption has been linked to the prevention of oxidative stress-induced diseases. OBJECTIVE: In this study, in vitro antioxidant activities of blueberry, jackfruit, blackberry, black raspberry, red raspberry, strawberry, and California table grape extracts were evaluated. MATERIALS AND METHODS: Antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant potential (FRAP), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), nitric oxide (NO), superoxide anion (O2-) scavenging assays, and ferric reducing power. RESULTS: Black raspberry extract had the highest phenolic (965.6 ± 2.9 mg gallic acid equivalents [GAE]/g), flavonoid (186.4 ± 1.7 mg quercetin equivalents/g), and proanthocyanidin (2677 ± 71.1 mg GAE/g) contents. All fruit extracts exhibited increasing radical scavenging activities with increased concentrations. At 100 µg/ml, red raspberry extract showed the highest ferric reducing power (A700 =0.3 ± 0.0052) and FRAP activity (A593 =11.43 mM Fe2+/g). Black raspberry extract (100 µg/ml) exhibited the highest DPPH activity (A517 =89.03 ± 0.0471). Jackfruit extract (100 µg/ml) had the highest ABTS (A734 =35.6 ± 0.613), NO (A540 =81.7 ± 0.2), and O2- radical scavenging (A230 =55.5 ± 0.2) activities. Positive correlations were observed between IC50 values for different radical scavenging activities and different polyphenolics. Red raspberry extract had the highest Pearson's coefficient values (0.952-1) between total phenolics, flavonoids, and proanthocyanidins and DPPH and superoxide radical scavenging activities. CONCLUSIONS: The antioxidant rich fruits in this study are good source of functional food and nutraceuticals that have the potential to improve human health. SUMMARY: All fruit extracts exhibited increasing radical scavenging activities with increased concentrationsBlack raspberry extract is enriched in total phenols, flavonoids, and proanthocyanidins and showed the highest 2,2-diphenyl-1-picrylhydrazyl scavenging activity and red raspberry extract showed the highest ferric reducing power and ferric reducing antioxidant potential activityJackfruit extract exhibited the highest 2,2'azino-bis (3-ethylbenzothiazoline-6-sulfonicacid) diammonium salt, nitric oxide, O2- scavenging activitiesPositive correlations were observed between IC50 values for different radical scavenging activities and different polyphenolics. Abbreviations Used: Abs: Absorbance, ABTS: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, BHT: Butylated hydroxytoluene, DPPH: 2,2-diphenyl-1-picrylhydrazyl, DW: Dry weight, FRAP: Ferric reducing antioxidant potential, FW: Fresh weight, GAE: Gallic acid equivalents, NADH: ß-nicotinamide adenine dinucleotide hydrate, NFL: The National Food Laboratories, NO: Nitric oxide, ONPG: ortho-nitrophenyl-ß-galactoside, PBS: Phosphate buffered saline, PMS: Phenazine methosulfate, QE: Quercetin equivalents, ROS: Reactive oxygen species, SD: Standard deviation, SOD: Superoxide dismutase, TCA: Trichloroacetic acid, TPTZ: 2,4,6-tris(2-pyridyl)-s-triazine, Trolox: (±)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid.

Marijuana Compounds: A Nonconventional Approach to Parkinson's Disease Therapy.

Parkinson's disease (PD), a neurodegenerative disorder, is the second most common neurological illness in United States. Neurologically, it is characterized by the selective degeneration of a unique population of cells, the nigrostriatal dopamine neurons. The current treatment is symptomatic and mainly involves replacement of dopamine deficiency. This therapy improves only motor symptoms of Parkinson's disease and is associated with a number of adverse effects including dyskinesia. Therefore, there is unmet need for more comprehensive approach in the management of PD. Cannabis and related compounds have created significant research interest as a promising therapy in neurodegenerative and movement disorders. In this review we examine the potential benefits of medical marijuana and related compounds in the treatment of both motor and nonmotor symptoms as well as in slowing the progression of the disease. The potential for cannabis to enhance the quality of life of Parkinson's patients is explored.

A new tool for analysis of root growth in the spatio-temporal continuum.

• Quantification of overall growth and local growth zones in root system development is key to understanding the biology of plant growth, and thus to exploring the effects of environmental, genotypic and mutational variations on plant development and productivity. • We introduce a methodology for analyzing growth patterns of plant roots from two-dimensional time series images, treating them as a spatio-temporal three-dimensional (3D) image volume. The roots are segmented from the images and then two types of analysis are performed: 3D spatio-temporal reconstruction analysis for simultaneous assessment of initiation and growth of multiple roots; and spatio-temporal pixel intensity analysis along root midlines for quantification of the growth zones. • The test measurements show simultaneous emergence of basal roots but sequential emergence of lateral roots in Phaseolus vulgaris, while lateral roots of Cicer arietinum emerge in a rhythmic pattern. Local growth analysis reveals multimodal transient growth zone in basal roots. At the initial stages after emergence, the roots oscillate rapidly, which slows down with time. • The methodology presented here allows detailed characterization of the phenomenology of roots, providing valuable information of spatio-temporal development, with applications in a wide range of growing plant organs.

Spatio-temporal analysis of development of basal roots of common bean (Phaseolus vulgaris L.).

Temporal development of roots is key to the understanding of root system architecture of plants which influences nutrient uptake, anchorage and plant competition. Using time lapse imaging we analyzed developmental patterns of length, growth angle, depth and curvature of Phaseolus basal roots from emergence till 48 h in two genotypes, B98311 and TLP19 with contrasting growth angles. In both genotypes all basal roots appeared almost simultaneously, but their growth rates varied which accounted for differences in root length. The growth angles of the basal roots fluctuated rapidly during initial development due to oscillatory root growth causing local bends. Beyond 24 h, as the root curvature stabilized, so did the growth angle. Therefore growth angle of basal roots is not a very reliable quantity for characterizing root architecture, especially during early seedling development. Comparatively, tip depth is a more robust measure of vertical distribution of the basal roots even during early seedling development.