Stilbenes: a journey from folklore to pharmaceutical innovation.

In modern times, medicine is predominantly based on evidence-based practices, whereas in ancient times, indigenous people relied on plant-based medicines with factual evidence documented in ancient books or folklore that demonstrated their effectiveness against specific infections. Plants and microbes account for 70% of drugs approved by the USFDA (U.S. Food and Drug Administration). Stilbenes, polyphenolic compounds synthesized by plants under stress conditions, have garnered significant attention for their therapeutic potential, bridging ancient wisdom with modern healthcare. Resveratrol, the most studied stilbene, initially discovered in grapes, red wine, peanuts, and blueberries, exhibits diverse pharmacological properties, including cardiovascular protection, antioxidant effects, anticancer activity, and neuroprotection. Traditional remedies, documented in ancient texts like the Ayurvedic Charak Samhita, foreshadowed the medicinal properties of stilbenes long before their modern scientific validation. Today, stilbenes are integral to the booming wellness and health supplement market, with resveratrol alone projected to reach a market value of 90 million US$ by 2025. However, challenges in stilbene production persist due to limited natural sources and costly extraction methods. Bioprospecting efforts reveal promising candidates for stilbene production, particularly endophytic fungi, which demonstrate high-yield capabilities and genetic modifiability. However, the identification of optimal strains and fermentation processes remains a critical consideration. The current review emphasizes the knowledge of the medicinal properties of Stilbenes (i.e., cardiovascular, antioxidant, anticancer, anti-inflammatory, etc.) isolated from plant and microbial sources, while also discussing strategies for their commercial production and future research directions. This also includes examples of novel stilbenes compounds reported from plant and endophytic fungi.

Maternal candidate gene variants, epigenetic factors, and susceptibility to idiopathic recurrent pregnancy loss: A systematic review.

BACKGROUND: Recurrent pregnancy loss is defined as the loss of two or more pregnancies and is a distressing condition for couples. OBJECTIVE: To investigate the relationship between variants in the candidate susceptibility genes and epigenetic factors to identify risk factors for idiopathic recurrent pregnancy loss (iRPL). SEARCH STRATEGY: A systematic literature search was performed using PubMed, Google Scholar, ScienceDirect, and Scopus databases. Insilico analysis was carried out using ShinyGO and STRING software. SELECTION CRITERIA: Research papers examining the association between variations in genetic and epigenetic factors and iRPL. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two authors. MAIN RESULTS: In total, 83 research papers were finally selected for the present study. Among all the genes involved in the pathogenesis of recurrent pregnancy loss, polymorphisms in IL superfamily genes, VEGF, ESR, and MTHFR were the most investigated. CONCLUSION: Polymorphisms in angiogenesis, immune tolerance, and thrombophilia pathway genes, which occur independently or synergistically, may lead to various complications during fetal development. Identification of multi-allele risk variants and epigenetic factors in women will be helpful in the identification of high-risk pregnancies. PROSPERO REGISTRATION NUMBER: Prospero CRD42021287315.

Factors affecting stress levels in parents of surgical neonates: A prospective observational study.

BACKGROUND: There is a paucity of research focusing on the stress levels in parents of newborns undergoing surgery. Resource challenged systems have to deal with overcrowding, a shortage of workforce along with demographic and socioeconomic issues like delayed presentations and out of pocket expenses. The primary objective of this study was to understand the factors associated with stress in the parents of these congenitally malformed neonates. METHODOLOGY: This was a prospective cohort study, which was conducted in a neonatal surgical ICU of a tertiary care teaching hospital. Factors affecting stress levels in parents of surgical neonates were studied in 100 participants. A multi-dimensional questionnaire - The PSS: NICU score was utilized in the study. The parents were interviewed on Day 3-5 after surgery. RESULT: 59% of the respondents were fathers. The majority of the parents were in the age bracket of 24 to 35 years. The mean scores for the subscales sights and sounds, looks and behavior and alteration in the parental role were 3.24±0.8, 3.52±0.63, 3.55±0.8 and 2.8 ± 0.9 respectively. The highest level of stress was found in the domains of alteration of parental role and infant appearance and behavior. Comparisons showed significantly higher maternal scores in all the domains. Overall stress scores were highest for abdominal wall defects. CONCLUSION: Parents of neonates undergoing surgery suffer from significant stress levels and appropriate counseling targeted towards specific stressors is required to allay this important parental issue.

Music as an aid to Allay Anxiety in Patients Undergoing Orthopedic Surgeries under Spinal Anesthesia.

Introduction: Patients undergoing surgery are anxious owing to the surgery, anesthesia, and unfamiliar environment of the operation theater. This anxiety can hamper the health and recovery of the patients. Among various nonpharmacologic modalities available, music can be used as a coping strategy to change uncomfortable conditions to the pleasant ones. Aims: To evaluate the role of music on perioperative anxiety, hemodynamic parameters, and patient satisfaction in patients undergoing orthopedic surgeries under spinal anesthesia. Settings and design: Tertiary care hospital, randomized control trial. Materials and methods: : The study was conducted after approval by Hospital Ethical Committee on 70 adult patients of either gender scheduled to undergo lower limb surgeries under spinal anesthesia. In group M (n = 35), patients listened to standard relaxation music, and in group C (n = 35), patients listened to standard operation theater noise tape through noise canceling headphones. The intraoperative hemodynamic parameters were recorded. Perioperative anxiety was assessed using visual analog scale for anxiety. Sedation score was observed using observer's assessment of alertness/sedation scale. Patient's satisfaction was also assessed in both the groups. Statistical analysis: Student t test, Chi-squared test, and paired sample t test. Results: : In group M, heart rate was lower when compared with group C. The difference was statistically significant at 10 minutes of assessment (P = 0.003) and statistically highly significant (P < 0.001) for rest of the time period. Statistically significant lower respiratory rate was there in group M when compared with group C (P = 0.05). Patients were more satisfied in the music group when compared with control group. Conclusion: The potential of music therapy can be used to allay patient anxiety, stabilize hemodynamics, and improve patient satisfaction.

Increased incidence of spontaneous abortions on exposure to cadmium and lead: a systematic review and meta-analysis.

BACKGROUND: Spontaneous abortions are the most severe complication of early pregnancy and are a major reproductive health problem. Although this could be caused due to various cytogenetic, immunological, or endocrinological reasons, role of environmental toxicants cannot be ruled out. In order to explore the role of cadmium and lead in causing spontaneous abortions, current systematic review and meta-analysis had been carried out. METHODOLOGY: Literature search was performed using appropriate keywords in PubMed, Science Direct, Cochrane Library, and Google Scholar databases up to December 25 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Metananalysis was carried out with the help of RevMan software (version 5.3). RESULTS: Meta-analysis of nine studies on cadmium concentrations in blood of women with at least one spontaneous abortions and controls revealed standardized mean difference (SMD)=3.39, 95% CI (2.17, 4.61), with p < .05. Similarly, meta-analysis of eight studies on lead concentrations revealed standardized mean difference (SMD)=6.24, 95% CI (4.34, 8.14), with p < .05. CONCLUSION: Populations exposed to heavy metals such as cadmium and lead are at higher risk of pregnancy loss. Therefore, couples experiencing repeated pregnancy losses may be screened for heavy metal load.

Symptoms, risk factors, diagnosis and treatment of urinary tract infections.

Urinary tract infection (UTI) is a common microbial infection found in all ages and sexes which involves inflammation of the urinary tract. These infections can range from simple bladder inflammation, that is, cystitis, to severe cases of uroseptic shock. UTI ranks as the number 1 infection that leads to a prescription of antibiotics after a doctor's visit. These infections are sometimes distressing and even life threatening, and both males (12%) and females (40%) have at least one symptomatic UTI throughout their lives. Diagnostic failures in case of bacterial infections are the main contributing factor in improper use of antibiotics, delay in treatment and low survival rate in septic conditions. So, early diagnosis and appropriate therapy with antibiotics are the most significant requirements for preventing complicated UTI conditions such as urosepsis. This review article summarises the symptoms of the UTIs and the associated risk factors to it. The various conventional and recent diagnostic methods were also discussed in this review, along with treatment therapies with or without antibiotics.

Rhodamine-based fluorescent probe for sequential detection of Al3+ ions and adenosine monophosphate in water.

Organic nanoparticles (N1) were prepared by dispersing thiophene-conjugated rhodamine derivative 1 in a buffer solution (10 mM TRIS, pH 7.4, containing 1% DMSO, v/v). N1 selectively recognized Al3+ ions through the "OFF-ON" switching mechanism of the spirolactam ring in rhodamine. The resulting N1·Al3+ complex recognized the biologically important molecule adenosine monophosphate (AMP) through a cation displacement process with a detection limit of 2 nM. N1 was capable of determining the concentration of Al3+ ions in environmental and biological samples. Portable test strips of N1 were prepared for the recognition of Al3+ ions and AMP for practical uses. Furthermore, it was demonstrated that the N1·Al3+ complex facilitated real-time monitoring of AMP concentration in the hydrolysis of ATP and ADP.

Modulation of biochemical and physiological parameters in Hordeum vulgare L. seedlings under the influence of benzyl-butyl phthalate.

BACKGROUND: Phthalates are man-made chemical compounds with numerous applications especially known for their use as plasticizers. They have weak bonding to the polymeric matrix or products in which they are used. Owing to this reason, they are readily released into the environment which makes them ubiquitous. The agricultural soils are also reported to be polluted with phthalates up to a considerable extent which causes adverse effects on flora and fauna. A few studies have been conducted on phthalate-induced phytotoxicity, which has revealed that phthalates affect the quality and yield of edible plants. In the last decades, some crops were analyzed for phthalate-induced adversities; among them, barley was the least explored. METHODS: The present study has investigated the impact of benzyl-butyl phthalate (BBP) on barley (Hordeum vulgare L.) seedlings to address the biochemical, physiological consequences, and toxicological implications. After the exogenous exposure of BBP (viz. 0, 25, 50, 100, 200, 400, 800, 1,600 mg/L) for 7 days, barley seedlings were analyzed for different indices. RESULTS: The exposure of BBP mediated a significant (p ≤ 0.05, 0.01) overall elevation in the contents of pigment, proline, soluble protein, carbohydrate, hydrogen peroxide (H2O2), and malondialdehyde (MDA) in shoots and roots of barley seedlings. The activities of superoxide dismutase (SOD), guaiacol peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) were also stimulated significantly in shoots and roots of seedlings against BBP stress except for SOD activity which declined in the roots. The polyphenols (non-enzymatic antioxidants) content was also altered in all the treated concentrations as compared to the control. Furthermore, BBP caused stomatal abnormalities, induced cytotoxicity, and loss of plasma membrane integrity. CONCLUSIONS: BBP disturbed the normal physiology of barley which could also affect the yield of the crop under field conditions.

Multi-residue pesticides analysis in water samples using reverse phase high performance liquid chromatography (RP-HPLC).

India is one of the leading suppliers of agrochemicals and has the largest pesticide industry in Asia. Among various Indian states, Punjab is the primary user of pesticides. Presence of pesticide residue in water and food products of Punjab is well documented. The present study was designed to envisage the level of pesticide contamination in pond water of eleven villages of Amritsar district of Punjab, India. A rapid and concurrent method for the identification and quantification of pesticides in water samples was developed and validated. The method validation parameters exhibited high sensitivity of the developed method and the proficiency for the identification and quantification of pesticide residues in water samples. The RP-HPLC method described here •is a novel method which is applicable for simple, rapid and precise detection of pesticides.•40.02% of water samples were found contaminated with multi-residue pesticides.•carbofuran was the most abundant pesticide which was present in 18.18% samples.

Purification of a dimeric arginine deiminase from Enterococcus faecium GR7 and study of its anti-cancerous activity.

The arginine deiminase (ADI, E.C 3.5.3.6) - a key enzyme of ADI pathway of Enterococcus faecium GR7 was purified to homogeneity. A sequential purification strategy involving ammonium sulfate fractionation, molecular sieve followed by Sephadex G-100 gel filtration was applied to the crude culture filtrate to obtain a pure enzyme preparation. The enzyme was purified with a fold of 16.92 and showed a final specific activity of 76.65IU/mg with a 49.17% yield. The dimeric ADI has a molecular mass of about 94,364.929Da, and comprises of hetrodimers of 49.1kDa and 46.5kDa as determined by MALDI-TOF and PAGE analysis. To assess anti-cancerous activity of ADI by MTT assay was carried out against cancer cell lines (MCF-7, Sp2/0-Ag14 and Hep-G2). Purified ADI exhibited the most profound antiproliferative activity against Hep-G2 cells; with half-maximal inhibitory concentration (IC50) of 1.95µg/ml. Purified ADI from E. faecium GR7 was observed to induce apoptosis in the Hep-G2 cells by DNA fragmentation assay. Our findings suggest the possibility of a future use of ADI from E. faecium GR7 as a potential anticancer drug.

Polymorphic variation in glutathione-S-transferase genes and risk of chronic myeloid leukaemia in the Kashmiri population.

Cancer is a complex disease and the genetic susceptibility to it could be an outcome of the inherited difference in the capacity of xenobiotic metabolizing enzymes. Glutathione-S-transferases (GSTs) are phase II metabolizing enzymes whose various genotypes have been associated with increased risk of different types of cancer. Null mutations caused by the deletion of the entire gene result in the absence of the enzymatic activity and increase in the risk of developing cancer including chronic myeloid leukaemia (CML). In the present case-control study we evaluated the effect of null mutations in GSTM1 and GSTT1 genes on the risk of developing CML. The study included 75 CML patients (43 males and 32 females; age (mean ± S.D) 42.3 ± 13.4 years) and unrelated non-malignant controls (76 male and 48 females; age (mean ± S.D) 41.5 ± 12.9). The distribution of GSTM1 and GSTT1 genotypes in CML patients and controls was assessed by multiplex-PCR method. Logistic regression was used to assess the relationship between GSTM1 and GSTT1 genotypes and risk of CML. Chi-square test was used to evaluate the trend in modulating the risk to CML by one or more potential high risk genotype. Although GSTM1 null genotype frequency was higher in CML patients (41%) than in the controls (35%), it did not reached a statistical significance (OD = 1.32, 95% CI: 0.73-2.40; P value = 0.4295). The frequency of GSTT1 null genotypes was higher in the CML patients (36%) than in the controls (21%) and the difference was found to be statistically significant (OD = 2.12, 95% CI: 1.12-4.02; P value = 0.0308). This suggests that the presence of GSTT1 genotype may have protective role against the CML. We found a statistically significant (OD = 3.09, 95% CI: 1.122-8.528; P value = 0.0472) interaction between the GSTM1 and GSTT1 null genotypes and thus individuals carrying null genotypes of both GSTM1 and GSTT1 genes are at elevated risk of CML.

Osteopontin: a potentially important therapeutic target in cancer.

INTRODUCTION: Cancer is an extremely complex disease and most cancer treatments are limited to chemotherapy, radiation and surgery. The progression of tumours towards malignancy requires the interaction of various cytokines, growth factors, transcription factors and effector molecules. Osteopontin is a cytokine-like, calcium-binding, extracelular-matrix- associated member of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family of proteins. It plays an important role in determining the oncogenic potential of various cancers. The role of osteopontin in various pathophysiological conditions suggests that the alteration in post-translational modification result in different functional forms that might change its normal physiological functions. AREAS COVERED: Osteopontin -based anticancer therapy, which may provide a new insight for the effective management of cancer. EXPERT OPINION: A better understanding of the signalling mechanism by which osteopontin promotes tumourigenesis may be useful in crafting novel osteopontin -based anticancer therapy. The role of osteopontin in promoting cancer progression is the subject of in depth investigation and thus targeting osteopontin might be a suitable therapeutic approach for the treatment of cancer.

Personality changes and the role of counseling in the rehabilitation of patients with laryngeal cancer.

We conducted a study of 65 adults who had undergone laryngectomy for the treatment of laryngeal cancer. Our goal was to identify any abnormal personality traits in these patients and to assess the effect that psychological counseling might have on correcting these abnormalities and thereby improving postoperative voice rehabilitation. A Personality Trait Inventory (PTI) administered to all patients preoperatively identified 47 patients who had abnormal scores for at least three personality traits. These 47 patients were sent for preoperative psychological counseling, and 3 months following surgery, they underwent a follow-up PTI. At the follow-up assessment, 40 of these patients-32 men and 8 women-still registered abnormal scores for at least three traits. Half of the men and half of the women were randomized to receive 12 sessions of individualized psychological counseling over 6 months in addition to standard speech therapy (group I); the other patients received speech therapy only (group II). A follow-up PTI was administered at the completion of psychological counseling and/or speech therapy (postoperative month 9). Statistical analysis of the data was performed with the paired-samples test. Intragroup analysis of the follow-up PTI results revealed that both groups experienced a significant improvement in activity scores (p < 0.001) compared with their previous PTI results and that group I had significantly better scores for two other PTI traits-cyclothymia (mood swings) and depressive tendency (p < 0.05); neither group showed a significant improvement in dominance scores. Intergroup comparisons revealed that group I's activity and depressive tendency scores were significantly better than those of group II; there was no significant difference between the two groups in cyclothymia and dominance scores. Finally, comparison of results by sex, regardless of group, revealed that men had a significantly higher score for dominance and women had significantly higher scores for depressive tendency, emotional instability, introversion, and social desirability. We conclude that a preoperative personality analysis should be carried out in all patients scheduled for laryngectomy to identify those with personality problems that might benefit from psychological counseling. Correction of these problems should help in the physical, mental, vocational, and social rehabilitation of these patients.

Osteopontin: an emerging therapeutic target for anticancer therapy.

Distant migration of malignant cells or metastasis is considered one of the hallmarks of tumour progression and makes cancer a most deadly disease. The elevated expression of osteopontin (OPN), a metastasis-associated small integrin-binding ligand N-linked glycoprotein family member has been observed in several cancers and, thus, this protein is considered as a potent prognostic marker during tumour progression. OPN regulates a series of signalling cascades and augments the expression of several oncogenic molecules. Therefore, understanding the molecular mechanism and the signalling pathways by which OPN promotes tumorigenesis may be helpful in designing a novel anticancer therapy. At present, the role of OPN in regulating cancer progression is the subject of intense investigation and targeting OPN might be an appropriate therapeutic strategy for the treatment of cancer. This review is focused on OPN-based anticancer therapy, which may provide a new dimension for the successful treatment of cancer.

Detection of microsatellite alterations in bronchial washings in squamous cell lung cancer: the first study from India.

BACKGROUND: In recent times, the possibility of detecting lung cancer using microsatellite alterations (microsatellite instability and loss of heterozygosity) in DNA of bronchial washings has been explored. However, no data regarding the presence of microsatellite alterations in lung cancer are available from India, a country which contributes significantly to the lung cancer burden of the world. METHODS: Bronchial washings as well as tumor specimens obtained on bronchoscopy were analyzed for the presence of loss of heterozygosity (LOH) and microsatellite instability (MSI) using the D3S1300 microsatellite marker on chromosome 3p and the TP53 marker on chromosome 17p. RESULTS: The sensitivities of the TP53 and D3S1300 loci in bronchial washings were 35% and 45% (combined 50%), respectively, which was significantly better than conventional cytology (positive for malignant cells in 15%). The presence of these microsatellite alterations was not related to the age, cumulative smoking exposure or smoking status (current or former) of patients. CONCLUSION: Microsatellite alterations, particularly LOH, occur in a significant proportion of Indian patients with squamous cell carcinoma of the lung.