Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach.

Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.

Transcriptomics, Cheminformatics, and Systems Pharmacology Strategies Unveil the Potential Bioactives to Combat COVID-19.

Coronavirus disease (COVID-19) is a viral disease caused by the SARS-CoV-2 virus and is becoming a global threat again because of the higher transmission rate and lack of proper therapeutics as well as the rapid mutations in the genetic pattern of SARS-CoV-2. Despite vaccinations, the prevalence and recurrence of this infection are still on the rise, which urges the identification of potential global therapeutics for a complete cure. Plant-based alternative medicine is becoming popular worldwide because of its higher efficiency and minimal side effects. Yet, identifying the potential medicinal plants and formulating a plant-based medicine is still a bottleneck. Hence, in this study, the systems pharmacology, transcriptomics, and cheminformatics approaches were employed to uncover the multi-targeted mechanisms and to screen the potential phytocompounds from significant medicinal plants to treat COVID-19. These approaches have identified 30 unique COVID-19 human immune genes targeted by the 25 phytocompounds present in four selected ethnobotanical plants. Differential and co-expression profiling and pathway enrichment analyses delineate the molecular signaling and immune functional regulations of the COVID-19 unique genes. In addition, the credibility of these compounds was analyzed by the pharmacological features. The current holistic finding is the first to explore whether the identified potential bioactives could reform into a drug candidate to treat COVID-19. Furthermore, the molecular docking analysis was employed to identify the important bioactive compounds; thus, an ultimately significant medicinal plant was also determined. However, further laboratory evaluation and clinical validation are required to determine the efficiency of a therapeutic formulation against COVID-19.

Comparison of serum protein profiles between major depressive disorder and bipolar disorder.

BACKGROUND: Major depressive disorder and bipolar disorder are prevalent and debilitating psychiatric disorders that are difficult to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. Quantitative protein profile analysis might help to objectively distinguish between these disorders and increase our understanding of their pathophysiology. Thus, this study was conducted to compare the peripheral protein profiles between the two disorders. METHODS: Serum samples were collected from 18 subjects with major depressive disorder and 15 subjects with bipolar disorder. After depleting abundant proteins, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification were performed. Data-dependent acquisition data were statistically analysed from the samples of 15 subjects with major depressive disorder and 10 subjects with bipolar disorder who were psychotropic drug-free. Two-sided t-tests were performed for pairwise comparisons of proteomes to detect differentially-expressed proteins (DEPs). Ingenuity Pathway Analysis of canonical pathways, disease and functions, and protein networks based on these DEPs was further conducted. RESULTS: Fourteen DEPs were significant between subjects with major depressive disorder and those with bipolar disorder. Ras-related protein Rab-7a (t = 5.975, p = 4.3 × 10- 6) and Rho-associated protein kinase 2 (t = 4.782, p = 8.0 × 10- 5) were significantly overexpressed in subjects with major depressive disorder and Exportin-7 (t = -4.520, p = 1.5 × 10- 4) was significantly overexpressed in subjects with bipolar disorder after considering multiple comparisons. Bioinformatics analysis showed that cellular functions and inflammation/immune pathways were significantly different. CONCLUSIONS: Ras-related protein Rab-7a, Rho-associated protein kinase 2, and Exportin-7 were identified as potential peripheral protein candidates to distinguish major depressive disorder and bipolar disorder. Further large sample studies with longitudinal designs and validation processes are warranted.

Exogenous salicylic acid improves freezing tolerance of spinach (Spinacia oleracea L.) leaves.

Salicylic acid (SA)-treatment has been reported to improve plant tolerance to various abiotic stresses. However, its effect on freezing tolerance has not been well investigated. We investigated the effect of exogenous SA on freezing tolerance of spinach (Spinacia oleracea L.) leaves. We also explored if nitric oxide (NO) and/or hydrogen peroxide (H2O2)-mediation was involved in this response, since these are known as primary signaling molecules involved in many physiological processes. A micro-centrifuge tube-based system used to apply SA to petiolate spinach leaves (0.5 mM over 4-d) was effective, as evident by SA content of leaf tissues. SA-treatment did not hamper leaf growth (fresh and dry weight; equatorial and longitudinal length) and was also not significantly different from 25% Hoagland controls vis-à-vis growth. SA application significantly improved freezing tolerance as evidenced by reduced ion-leakage and alleviated oxidative stress (lower accumulation of O2·- and H2O2) following freeze-thaw stress treatments (-6.5, -7.5, and -8.5 °C). Improved freezing tolerance of SA-treated leaves was paralleled by increased proline and ascorbic acid (AsA) accumulation. A 9-d cold acclimation (CA) treatment also improved leaf freezing tolerance (compared to non-acclimated control) and was accompanied by accumulation of SA and proline. Our results indicate that increased freezing tolerance may be associated with accumulation of compatible solutes (proline) and antioxidants (AsA). Notably, the beneficial effect of SA on freezing tolerance was abolished when either H2O2- or NO-scavenger (1 µM N-acetylneuraminic acid, NANA or 100 µM hemoglobin, HB, respectively) was added to SA as pretreatment. Our data suggest that SA-induced freezing tolerance in spinach may be mediated by NO and H2O2 signaling.

Differences in cold hardiness, carbohydrates, dehydrins and related gene expressions under an experimental deacclimation and reacclimation in Prunus persica.

To boost our understanding of a recent outbreak of freezing injury, we sought to confirm distinctive features between the shoot tissues of the peach (Prunus persica) cultivars Daewol and Kiraranokiwami by mimicking unseasonable changes of temperatures that occur in the early spring through repeated deacclimation and reacclimation treatments. Patterns of cold hardiness declined dramatically during the deacclimation and rose during the reacclimation in both cultivars. Our results indicated that 'Daewol' possessed higher capacity in response to repeated deacclimation and reacclimation treatments than 'Kiraranokiwami'. 'Daewol' showed more sensitive changes in the carbohydrates in response to warm and low temperatures compared with 'Kiraranokiwami'. 'Daewol' indicated almost similar repeated down- and up-patterns in soluble sugar content in response to repeated deacclimation and reacclimation, whereas it indicated repeated up- and down-patterns in starch content. However, 'Kiraranokiwami' showed a progressive increase in the soluble sugar content and a progressive decrease in starch content. Notably, patterns of accumulation of a 60-kDa dehydrin protein encoded by the PpDhn1 gene were confirmed through western blotting and paralleled fluctuations of cold hardiness in both cultivars. Expression of this dehydrin was weak in both cultivars during deacclimation but its band intensity increased during reacclimation. Changes in related genes (ß-amylase, PpDhn1, PpDhn2 and PpDhn3) were positively correlated with changes in cold hardiness throughout the experiment. Our results indicate that recent repeated warm periods may cause premature deacclimation in the early spring, and that more cold-tolerant cultivar may be more resilient to freezing injury caused by unstable temperature conditions.

Physiological and metabolic analyses reveal the proline-mediated flowering delay mechanism in Prunus persica.

Peaches are susceptible to various environmental stresses. Particularly in late spring, freezing temperatures can damage peaches and consequently, affect their productivity. Therefore, flowering delay is a prominent strategy for avoiding spring frost damage. Our previous study confirmed that treatment with 5% sodium alginate and 100 mM CaCl2 (5AG) to avoid frost damage during the blooming stage delays flowering. To reveal the flowering delay mechanism of peaches, this study systematically analyzed the modification of amino acid profiles in control and 5AG-treated peach plants at different day intervals. Our findings indicate that arginine (Arg), glutamate (Glu), and proline (Pro) levels differed between the control and 5AG-treated peach shoots throughout the phenological development of flower buds. Furthermore, two amino acids (Arg and Glu) are involved in the Pro pathway. Thus, using a computational metabolomics method, Pro biosynthesis and its characteristics, gene ontology, gene synteny, cis-regulatory elements, and gene organizations were examined to decipher the involvement of Pro metabolism in peach flowering delay. In addition, qRT-PCR analysis revealed the transcriptional regulation of Pro-related and flowering-responsive genes and their role in flowering delay. Overall, this pilot study provides new insights into the role of Pro in the flowering delay mechanisms in Prunus persica through 5AG treatment.

Effect of Bias Potential on the Interface of a Solid Electrolyte and Electrode during XPS Depth Profiling Analysis.

Depth profiling is an essential method to investigate the physical and chemical properties of a solid electrolyte and electrolyte/electrode interface. In conventional depth profiling, various spectroscopic tools such as X-ray photoelectron spectroscopy (XPS) and secondary ion mass spectroscopy (SIMS) are utilized to monitor the chemical states along with ion bombardment to etch a sample. Nevertheless, the ion bombardment during depth profiling results in an inevitable systematic error, i.e., the accumulation of mobile ions at the electrolyte/electrode interface, known as the ion pile-up phenomenon. Here, we propose a novel method using bias potential, the substrate-bias method, to prevent the ion pile-up phenomena during depth profiling of a solid electrolyte. When the positive bias potential is applied on the substrate (electrode), the number of accumulating ions at the electrolyte/electrode interface is significantly reduced. The in-depth XPS analysis with the biased electrode reveals not only the suppression of the ion pile-up phenomena but also the altered chemical states at the interfacial region between the electrolyte and electrode depending on the bias. The proposed substrate-bias method can be a good alternative scheme for an efficient yet precise depth profiling technique for a solid electrolyte.

Methyl jasmonate and salicylic acid as powerful elicitors for enhancing the production of secondary metabolites in medicinal plants: an updated review.

Plant secondary metabolites are bioactive scaffolds that are crucial for plant survival in the environment and to maintain a defense mechanism from predators. These compounds are generally present in plants at a minimal level and interestingly, they are found to have a wide variety of therapeutic values for humans. Several medicinal plants are used for pharmaceutical purposes due to their affordability, fewer adverse effects, and vital role in traditional remedies. Owing to this reason, these plants are exploited at a high range worldwide and therefore many medicinal plants are on the threatened list. There is a need of the hour to tackle this major problem, one effective approach called elicitation can be used to enhance the level of existing and novel plant bioactive compounds using different types of elicitors namely biotic and abiotic. This process can be generally achieved by in vitro and in vivo experiments. The current comprehensive review provides an overview of biotic and abiotic elicitation strategies used in medicinal plants, as well as their effects on secondary metabolites enhancement. Further, this review mainly deals with the enhancement of biomass and biosynthesis of different bioactive compounds by methyl jasmonate (MeJA) and salicylic acid (SA) as elicitors of wide medicinal plants in in vitro by using different cultures. The present review was suggested as a significant groundwork for peers working with medicinal plants by applying elicitation strategies along with advanced biotechnological approaches.

A Recent Update on the Impact of Nano-Selenium on Plant Growth, Metabolism, and Stress Tolerance.

Selenium (Se) is a microelement that plays an important nutrient role by influencing various physiological and biochemical traits in plants. It has been shown to stimulate plant metabolism, enhancing secondary metabolites and lowering abiotic and biotic stress in plants. Globally, the enormous applications of nanotechnology in the food and agricultural sectors have vastly expanded. Nanoselenium is more active than bulk materials, and various routes of synthesis of Se nanoparticles (Se-NPs) have been reported in which green synthesis using plants is more attractive due to a reduction in ecological issues and an increase in biological activities. The Se-NP-based biofortification is more significant because it increases plant stress tolerance and positively impacts their metabolism. Se-NPs can enhance plant resistance to various oxidative stresses, promote growth, enhance soil nutrient status, enhance plant antioxidant levels, and participate in the transpiration process. Additionally, they use a readily available, biodegradable reducing agent and are ecologically friendly. This review concentrates on notable information on the different modes of Se-NPs' synthesis and characterization, their applications in plant growth, yield, and stress tolerance, and their influence on the metabolic process.

Molecular Insights into Abiotic Stresses in Mango.

Mango (Mangifera indica L.) is one of the most economically important fruit crops across the world, mainly in the tropics and subtropics of Asia, Africa, and Central and South America. Abiotic stresses are the prominent hindrance that can adversely affect the growth, development, and significant yield loss of mango trees. Understanding the molecular physiological mechanisms underlying abiotic stress responses in mango is highly intricate. Therefore, to gain insights into the molecular basis and to alleviate the abiotic stress responses to enhance the yield in the mere future, the use of high-throughput frontier approaches should be tied along with the baseline investigations. Taking these gaps into account, this comprehensive review mainly speculates to provide detailed mechanisms and impacts on physiological and biochemical alterations in mango under abiotic stress responses. In addition, the review emphasizes the promising omics approaches in unraveling the candidate genes and transcription factors (TFs) responsible for abiotic stresses. Furthermore, this review also summarizes the role of different types of biostimulants in improving the abiotic stress responses in mango. These studies can be undertaken to recognize the roadblocks and avenues for enhancing abiotic stress tolerance in mango cultivars. Potential investigations pointed out the implementation of powerful and essential tools to uncover novel insights and approaches to integrate the existing literature and advancements to decipher the abiotic stress mechanisms in mango. Furthermore, this review serves as a notable pioneer for researchers working on mango stress physiology using integrative approaches.

Integrated omics profiling and network pharmacology uncovers the prognostic genes and multi-targeted therapeutic bioactives to combat lung cancer.

Non-small cell lung cancer (NSCLC) is the frequent subtype of lung cancer and the currently used treatment methods, diagnosis, and chemoresistance are relatively ineffective. Determining the pharmacological targets from active biomolecules of medicinal plants has become a frontiers era for biomedical research to develop novel therapies. In view of these scenarios, this pilot study, network pharmacology, cheminformatics, integrative omics, molecular docking and in vitro anti-cancer analysis were performed to unveil the multi-targeted treatment mechanisms of novel plant bioactives to treat lung cancer. Bioactive molecules from medicinal plants were compiled from PubChem. Network pharmacology approach revealed that 29 compounds efficiently target the 390 human and lung cancer associated genes. In addition, comparative analysis was performed and identified the 7 bioactive molecules significantly targeting 8 lung cancer genes. The integrative omics analysis discovered unique genes between the lung cancer and normal lung tissues. These genes were further validated through protein-protein interaction, gene ontology, gene functional and pathway enrichment, boxplot and overall survival analyses to understand the function of unique genes and their involvement in cancer signaling pathways. Survival heatmap analyses identified the significant prognostic genes. Docking results revealed that, lupeol and p-coumaric acid displayed high binding affinities with MIF, CCNB1, FABP4. Hence, we selected these two bioactives for in vitro analysis. Furthermore, these selected bioactives were showed concentration dependent cytotoxicity against the lung adenocarcinoma cells (A549). This holistic study has opened up novel avenues and unravels the cancer prognostic genes which could serve as druggable target and bioactives with anti-cancerous efficacy. Further functional validations are prerequisites to deciphering these bioactives as commercial drug candidates.

Understanding Macroalgae: A Comprehensive Exploration of Nutraceutical, Pharmaceutical, and Omics Dimensions.

Driven by a surge in global interest in natural products, macroalgae or seaweed, has emerged as a prime source for nutraceuticals and pharmaceutical applications. Characterized by remarkable genetic diversity and a crucial role in marine ecosystems, these organisms offer not only substantial nutritional value in proteins, fibers, vitamins, and minerals, but also a diverse array of bioactive molecules with promising pharmaceutical properties. Furthermore, macroalgae produce approximately 80% of the oxygen in the atmosphere, highlighting their ecological significance. The unique combination of nutritional and bioactive attributes positions macroalgae as an ideal resource for food and medicine in various regions worldwide. This comprehensive review consolidates the latest advancements in the field, elucidating the potential applications of macroalgae in developing nutraceuticals and therapeutics. The review emphasizes the pivotal role of omics approaches in deepening our understanding of macroalgae's physiological and molecular characteristics. By highlighting the importance of omics, this review also advocates for continued exploration and utilization of these extraordinary marine organisms in diverse domains, including drug discovery, functional foods, and other industrial applications. The multifaceted potential of macroalgae warrants further research and development to unlock their full benefits and contribute to advancing global health and sustainable industries.

Understanding Mutations in Human SARS-CoV-2 Spike Glycoprotein: A Systematic Review & Meta-Analysis.

Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive analyses of spike protein mutations in the significant variant clade of SARS-CoV-2, using the data available on the Nextstrain server. We selected various mutations, namely, A222V, N439K, N501Y, L452R, Y453F, E484K, K417N, T478K, L981F, L212I, N856K, T547K, G496S, and Y369C for this study. These mutations were chosen based on their global entropic score, emergence, spread, transmission, and their location in the spike receptor binding domain (RBD). The relative abundance of these mutations was mapped with global mutation D614G as a reference. Our analyses suggest the rapid emergence of newer global mutations alongside D614G, as reported during the recent waves of COVID-19 in various parts of the world. These mutations could be instrumentally imperative for the transmission, infectivity, virulence, and host immune system's evasion of SARS-CoV-2. The probable impact of these mutations on vaccine effectiveness, antigenic diversity, antibody interactions, protein stability, RBD flexibility, and accessibility to human cell receptor ACE2 was studied in silico. Overall, the present study can help researchers to design the next generation of vaccines and biotherapeutics to combat COVID-19 infection.

Pharmacokinetics of a fixed-dose glimepiride/sustained-release metformin combination.

OBJECTIVE: Pharmacokinetic (PK) profiles of glimepiride and metformin have been established for the combination drug as well as each agent individually. However, the PK profiles of a combination drug containing glimepiride and sustained-release (SR) metformin have not been reported. To compare the pharmacokinetic profiles of glimepiride/SR metformin (2 mg/500 mg) with the PK of immediate-release (IR) formulations, an open-label, randomized, 3-period, 3-sequence, 3-treatment, crossover study was conducted in 12 healthy subjects. METHODS: After a single administration of glimepiride/SR metformin 2 mg/500 mg (Treatment) or glimepiride/metformin IR 2 mg/500 mg (Reference 1), or administration of 2 doses of glimepiride/metformin IR 1 mg/250 mg 12 h apart (Reference 2), serial blood samples were collected and drug concentrations determined by liquid chromatography/ tandem mass spectrometry. PK parameters (Cmax and AUC24) for glimepiride and metformin were log-transformed and compared using a mixed-effects model analysis of variance (ANOVA). The mean differences and 95% confidence intervals (CIs) were back-transformed to obtain geometric mean ratios along with the CIs for the ratios. RESULTS: Treatment demonstrated similar systemic exposures for glimepiride; the geometric mean ratio (95% CIs) for glimepiride AUC24 was 1.05 (0.97 - 1.13) for Treatment relative to Reference 1 and 1.08 (1.00 - 1.17) for Treatment relative to Reference 2. The SR formulation showed a delay in the time to reach maximum concentration for metformin from 1.0 - 4.0 h to 4.0 - 8.0 h and a decreased AUC24 value; the geometric mean ratio for metformin AUC24 was 0.87 (0.74 - 1.03) for Treatment relative to Reference 1 and 0.75 (0.63 - 0.88) for Treatment relative to Reference 2. CONCLUSIONS: This study demonstrates for the first time that fixed-dose glimepiride and SR metformin 2 mg/500 mg shows a PK profile similar to that of glimepiride, but with a delayed time to maximum concentration and slightly decreased bioavailability for metformin compared with the IR fixed-dose combination, in healthy volunteers. PK profiles from this exploratory study will be helpful in designing and conducting further studies in diabetic patients.

Assessing the Anti-inflammatory Effects of Bacopa-Derived Bioactive Compounds Using Network Pharmacology and In Vitro Studies.

Bacopa monnieri is reported as a potent Indian medicinal plant that possesses numerous pharmacological activities due to the presence of various bioactive compounds. These pharmacological activities were used in the ancient medicine system to cure inflammatory conditions. Bacopa has the ability to reduce acute pain and inflammation by inhibiting the enzyme cyclo-oxygenase-2 (COX-2) and reducing COX-2-arbitrated prostanoid mediators. Moreover, the anti-inflammatory property may also be associated with the neuroprotective activity of Bacopa. Considering this importance, the current pilot study focused on the anti-inflammatory potential of various phytocompounds of bacopa and their interaction with inflammation responsible genes such as COX2, iNOS, LOX, STAT3, CCR1, and MMP9 through pharmacology analysis of its systems. Docking results revealed that, quercetin (QR) showed significant binding energies with inflammatory genes. Hence, we selected QR as a potential phytocompound for further in vitro experiments. This existing study aimed to evaluate the efficacy of QR as a potent anti-inflammatory compound against lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The in vitro analysis concludes that QR effectively reduces the production of nitric oxide (NO) in LPS-induced RAW264.7 cells and downregulates the expression of COX-2 and iNOS genes due to the inhibitory potential of QR on LPS-stimulated NO production.

Molecular Insights into Freezing Stress in Peach Based on Multi-Omics and Biotechnology: An Overview.

In nature or field conditions, plants are frequently exposed to diverse environmental stressors. Among abiotic stresses, the low temperature of freezing conditions is a critical factor that influences plants, including horticultural crops, decreasing their growth, development, and eventually quality and productivity. Fortunately, plants have developed a mechanism to improve the tolerance to freezing during exposure to a range of low temperatures. In this present review, current findings on freezing stress physiology and genetics in peach (Prunus persica) were refined with an emphasis on adaptive mechanisms for cold acclimation, deacclimation, and reacclimation. In addition, advancements using multi-omics and genetic engineering approaches unravel the molecular physiological mechanisms, including hormonal regulations and their general perceptions of freezing tolerance in peach were comprehensively described. This review might pave the way for future research to the horticulturalists and research scientists to overcome the challenges of freezing temperature and improvement of crop management in these conditions.

Global Integrated Genomic and Transcriptomic Analyses of MYB Transcription Factor Superfamily in C3 Model Plant Oryza sativa (L.) Unravel Potential Candidates Involved in Abiotic Stress Signaling.

Plant transcription factors (TFs) are significant players in transcriptional regulations, signal transduction, and constitute an integral part of signaling networks. MYB TFs are major TF superfamilies that play pivotal roles in regulation of transcriptional reprogramming, physiological processes, and abiotic stress (AbS) responses. To explore the understanding of MYB TFs, genome and transcriptome-wide identification was performed in the C3 model plant, Oryza sativa (OsMYB). This study retrieved 114 OsMYB TFs that were computationally analyzed for their expression profiling, gene organization, cis-acting elements, and physicochemical properties. Based on the microarray datasets, six OsMYB genes which were sorted out and identified by a differential expression pattern were noted in various tissues. Systematic expression profiling of OsMYB TFs showed their meta-differential expression of different AbS treatments, spatio-temporal gene expression of various tissues and their growth in the field, and gene expression profiling in responses to phytohormones. In addition, the circular ideogram of OsMYB genes in related C4 grass plants conferred the gene synteny. Protein-protein interactions of these genes revealed the molecular crosstalk of OsMYB TFs. Transcriptional analysis (qPCR) of six OsMYB players in response to drought and salinity stress suggested the involvement in individual and combined AbS responses. To decipher how these OsMYB play functional roles in AbS dynamics, further research is a prerequisite.

Cord Blood Proteomic Biomarkers for Predicting Adverse Neurodevelopmental Outcomes in Monoamniotic Twins.

Monoamniotic twins have a high risk of mortality and perinatal morbidity due to cord entanglement and vascular anastomosis. Despite efforts to reduce the mortality rate through intensive fetal surveillance and timed delivery, poor long-term neurodevelopmental outcomes remain an unsolved problem. This study aimed to identify novel biomarkers predicting abnormal neurodevelopmental outcomes in monoamniotic twins with cord blood samples taken at the time of delivery. Abnormal neurodevelopmental outcomes were defined as (1) a severe brain lesion on neonatal brain ultrasound, (2) developmental delay, (3) cerebral palsy, and/or (4) blindness or deafness. Cord blood was analyzed with mass spectrometry-based proteomics according to the neurodevelopmental outcomes. Statistical analysis was performed to determine the differentially expressed proteins between neonates with normal and abnormal neurodevelopmental outcomes. Several candidate proteins were further validated with enzyme-linked immunosorbent assays. A total of 20 neonates (10 pairs) of monoamniotic twins were included in the proteomic analysis, of which 25% had abnormal neurodevelopmental outcomes. Eighteen proteins were differentially expressed in neonates with abnormal neurodevelopmental outcomes. The upregulated proteins in the neonates with adverse neurodevelopmental outcome were immunoglobulin (Ig)-gamma-4 chain C region, apolipoprotein E, and alpha-fetoprotein. In contrast, Ig-lambda chain V region 4A, Ig-heavy variable 3, Ig-kappa chain C region, Ig-mu chain C region, C1q, ceruloplasmin, and Ig-lambda chain V-I region were decreased. In the validation experiment, the cord blood concentration of ceruloplasmin was significantly lower in neonates with adverse neurodevelopmental outcomes than in those without. Therefore, ceruloplasmin could be a useful predictive biomarker of adverse neurodevelopmental outcomes in monoamniotic twins.

Vitex negundo L. derived specialized molecules unveil the multi-targeted therapeutic avenues against COPD: a systems pharmacology approach.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease caused by increasing breathing passage obstruction which completely disrupts human homeostasis. Some patients require lung transplantation or long-term oxygen therapy. COPD is one of the noxious diseases and its fourth leading cause of death around the globe. There is an immediate need for potential drug development to tackle this serious disease. Folk medicines are used to combat complex diseases that have shown effectiveness in the treatment of breathing diseases. Vitex negundo L. is an ethnobotanically important medicinal plant used for various ailments and modulates human cellular events. This shrub has diverse specialized metabolites and is being used as complementary medicine in various countries. Though systems-level understanding is there on the mode of action, the multi-target treatment strategy for COPD is still a bottleneck. METHODS: In this investigation, systems pharmacology, cheminformatics, and molecular docking analyses were performed to unravel the multi-targeted mechanisms of V. negundo L. potential bioactives to combat COPD. RESULTS: Cheminformatics analysis combined with the target mining process identified 86 specialized metabolites and their corresponding 1300 direct human receptors, which were further imputed and validated systematically. Furthermore, molecular docking approaches were employed to evaluate the potential activity of identified potential compounds. In addition, pharmacological features of these bioactives were compared with available COPD drugs to recognize potential compounds that were found to be more efficacious with higher bioactive scores. CONCLUSIONS: The present study unravels the druggable targets and identifies the bioactive compounds present in V. negundo L., that may be utilized for potential treatment against COPD. However, further in vivo analyses and clinical trials of these molecules are essential to deciphering their efficacy.

Alterations in blood proteins in the prodromal stage of bipolar II disorders.

Although early intervention may help prevent the progression of bipolar disorder, there are some controversies over early pharmacological intervention. In this study, we recruited 40 subjects in the prodromal stage of BD-II (BP), according to bipolar at-risk state criteria. We compared the expression of their plasma proteins with that of 48 BD-II and 75 healthy control (HC) to identify markers that could be detected in a high-risk state. The multiple reaction monitoring method was used to measure target peptide levels with high accuracy. A total of 26 significant peptides were identified through analysis of variance with multiple comparisons, of which 19 were differentially expressed in the BP group when compared to the BD-II and HC groups. Two proteins were overexpressed in the BP group; and were related to pro-inflammation and impaired neurotransmission. The other under-expressed peptides in the BP group were related to blood coagulation, immune reactions, lipid metabolism, and the synaptic plasticity. In this study, significant markers observed in the BP group have been reported in patients with psychiatric disorders. Overall, the results suggest that the pathophysiological changes included in BD-II had already occurred with BP, thus justifying early pharmacological treatment to prevent disease progression.