Rajiv Gandhi Centre for Biotechnology
  • Thiruvananthapuram, India
Recent publications
Phytochemicals, the bioactive compounds derived from plants, play a significant role in modulating pathways leading to cancer and inflammation, rendering themselves promising candidates for therapeutic interventions. This review explores the multifaceted potential of various phytochemicals in modulating key mechanisms involved in the development and progression of cancer and inflammation. The diverse array of phytochemicals discussed here encompasses polyphenols, flavonoids, alkaloids, terpenoids, and many others, each with distinct molecular targets and modes of action. This review is an attempt to elucidate and correlate the regulatory role of phytochemicals on cellular signaling pathways implicated in oncogenesis and inflammatory responses, highlighting the significance and potential of phytochemical-based therapies for cancer prevention and treatment, as well as for managing inflammatory conditions. By exploring the promising potential of phytochemical-based remedies for cancer prevention, treatment, and inflammatory conditions and emphasizing their diverse roles in modulating critical regulatory mechanisms, this review addresses the current research landscape, challenges, and future directions in utilizing phytochemicals as effective agents against cancer and inflammation.
Nanocarriers for drugs have been investigated for decades, yet it is still challenging to achieve sustained release from nanomaterials due to drug loading inefficiency and burst release. In this study, we developed novel functional carbon dots (CDs) and investigated the therapeutic efficacy by studying the loading efficiency and release behavior of the anticancer drug doxorubicin (DOX). CDs were successfully synthesized using a one-step pyrolysis method with varying concentrations of citric acid (CA) and thiourea (TU). Functional groups, morphology, particle size, and zeta potential of synthesized CT-CDs and DOX loaded CT-CDs were investigated by UV–visible, Fluorescence, dynamic light scattering, Zeta Potential measurements, FTIR, and transmission electron microscopy. The zeta potential data revealed DOX loading onto CT-CDs by charge difference, i.e. −24.6 ± 0.44 mV (CT-CDs) and 20.57 ± 0.55 mV (DOX-CT-CDs). DOX was loaded on CDs with a loading efficiency of 88.67 ± 0.36%. In vitro drug release studies confirmed pH-dependent biphasic drug release, with an initial burst effect and sustained release of DOX was found to be 21.42 ± 0.28% (pH 5), 13.30 ± 0.03% (pH 7.4), and 13.95 ± 0.18% (pH 9) even after 144 h at 37 °C. The CT-CDs were non-toxic and biocompatible with L929 Fibroblasts cells. The cytotoxic effect of DOX-CT-CDs showed a concentration-dependent effect after 48 h with Glioblastoma U251 cells. Flow cytometry was used to examine the cellular uptake of CT-CDs and DOX-CT-CDs in L929 and U251 cells. It was observed that the maximum CT-CDs uptake was around 75% at the end of 24 h. This study showed that the synthesized fluorescent CT-CDs demonstrated a high drug loading capacity, pH-dependent sustained release of DOX, and high cellular uptake by mammalian cells. We believe this work provides practical and biocompatible CDs for chemotherapeutic drug delivery that can be applied to other drugs for certain therapeutic aims.
Introduction Black pepper (Piper nigrum L.) is a non-model spice crop of significant agricultural and biological importance. The ‘quick wilt’ disease caused by the oomycete Phytophthora capsici is a major threat, leading to substantial crop loss. The molecular mechanisms governing the plant immune responses to this pathogen remain unclear. This study employs RNA sequencing and transcriptome analysis to explore the defense mechanisms of P. nigrum against P. capsici. Results Two-month-old P. nigrum plantlets were subjected to infection with P. capsici, and leaf samples were collected at 6- and 12-hours post-inoculation. RNA was extracted, sequenced, and the resulting data were processed and assembled. Differential gene expression analysis was conducted to identify genes responding to the infection. Additionally, the study investigated the involvement of Salicylic acid (SA), Jasmonic acid (JA), and Ethylene (ET) signalling pathways. Our transcriptome assembly comprised 64,667 transcripts with 96.7% completeness, providing valuable insights into the P. nigrum transcriptome. Annotation of these transcripts identified functional categories and domains, provided details on molecular processes. Gene expression analysis identified 4,714 transcripts at 6 h post-infection (hpi) and 9,416 at 12 hpi as differentially expressed, revealing dynamic regulation of immune-related genes. Furthermore, the study investigated key genes involved in biosynthesis pathways of Salicylic acid, Jasmonic acid, and Ethylene signalling. Notably, we found differential regulation of critical genes associated with these pathways while comparing data before and after infection, thereby shedding light on their roles in defense mechanism in P. nigrum defense. Conclusions This comprehensive transcriptome analysis of P. nigrum response to P. capsici attack provides valuable insights into the plant defense mechanisms. The dynamic regulation of innate immunity and the involvement of key signalling pathways highlight the complexity of the plant-pathogen interaction. This study contributes to our understanding of plant immunity and offers potential strategies for enhancing P. nigrum resistance to this harmful pathogen.
Chronic diseases, non-communicable diseases, age-related diseases, the burden of diseases, and pandemics are never-ending problems that humans have been going through since our evolution. The biomedical field is continuously upgrading and making required changes that can decrease the incidence and mortality rate associated with such diseases. One persistent problem still needs to overcome which is the diagnosis of these diseases at its early stages such as at the cellular or molecular level. Efforts in terms of cellular biology such as DNA sequencing, and chromosome testing have been made over the years to understand and resolve the problem but still, we are facing the problem with an exponential increase in the number of these kinds of diseases. An appropriate and concrete revolution is a need of time. Vibrational spectroscopy with recent technological advancements proven a favorable disease diagnostic tool by researchers and practitioners in recent years. Raman spectroscopy, a vibrational spectroscopic tool is a label-free, reliably non-invasive, rapid, easy-to-use, efficient, and sensitive to biomolecular changes in the human body. This book chapter is a dedicated explanation of the Raman spectroscopic applications assisted by Artificial Intelligence methods which proved a never seen before advancement in disease diagnosis applications. We comprehensively studied all the variants of Raman spectroscopy such as Spontaneous, Surface Enhanced, Coherent Anti-Stokes, and Stimulated forms used in recent years, and their valuable contribution as compared to the standard medical tools. This chapter is intended for readers who want to learn about the deep-learning field of Artificial Intelligence and how it is contributing to the disease diagnosis process with the help of Raman spectroscopy. Through our efforts, we hope that we can trigger the right ruminating spots of the readers which by the end of this chapter can attempt to use and contribute to making the clinical transition of Raman spectroscopy a reality. Finally, we bid to make a revolution in the biomedical field by introducing Raman spectroscopy which can help to lessen the load of diseases to a great extent and make human life worth living as wholesome.
Black pepper (Piper nigrum L.), a highly valued spice crop, is economically significant as one of the most widely traded spices in the world. The global yield and quality of black pepper (Piper nigrum L.) are affected by foot rot-causing soil-borne oomycete pathogen Phytophthora capsici. To gain initial insights toward developing an approach that utilizes microbial genetic resources for controlling foot rot disease in black pepper, we mapped the rhizobiome communities in susceptible Piper nigrum L. and wild-resistant Piper colubrinum. The analysis showed compositional differences in the rhizobiome of two Piper species, which revealed higher diversity and the presence of more differentially abundant genera in P. colubrinum. Furthermore, P. colubrinum rhizobiome had a significantly higher abundance of known anti-oomycete genera, such as Pseudomonas, and a higher differential abundance of Janthinobacterium, Variovorax, and Comamonas, indicating their probable contribution to pathogen resistance. Predictive functional profiling in P. colubrinum rhizobiome showed highly enriched functional gene orthologs (KOs), particularly chemotaxis proteins, osmoprotectants, and other transport systems that aid in pathogen resistance. Similarly, pathways such as phenylpropanoid biosynthesis and other antimicrobial synthesis were enriched in P. colubrinum rhizobiome. The culturable diversity of the resistant root endosphere, which harbors efficient biocontrol agents such as Pseudomonas, strengthens the possible role of root microbiome in conferring resistance against soil-borne pathogens. Our results depicted a clear distinction in the rhizobiome architecture of resistant and susceptible Piper spp., suggesting its influence in recruiting bacterial communities that probably contribute to pathogen resistance.
In cervical cancer, loss of p53 or mutant non-functional p53 and hyperactivated mTOR/Akt pathway positively correlates to cancer progression. Urdamycin V isolated from Streptomyces OA293 is a recently isolated novel angucycline derivative that in the present study showcased induction of p53 independent apoptosis in both HPV (Human papillomavirus) positive and negative cervical cancer cell lines. Apoptosis induction was via phosphorylation modulation in the cell growth regulating proteins along mTORC2/Akt/p38/Erk pathway. The compound was also tested against human pathogens and selectively inhibited gram-positive strains, Streptococcus pyogenes and Staphylococcus aureus. The present study put forward urdamycins as a potential therapeutic that places promise for further research.
Burden of stroke differs by region, which could be attributed to differences in comorbid conditions and ethnicity. Genomewide variation acts as a proxy marker for ethnicity, and comorbid conditions. We present an integrated approach to understand this variation by considering prevalence and mortality rates of stroke and its comorbid risk for 204 countries from 2009 to 2019, and Genome-wide association studies (GWAS) risk variant for all these conditions. Global and regional trend analysis of rates using linear regression, correlation, and proportion analysis, signifies ethnogeographic differences. Interestingly, the comorbid conditions that act as risk drivers for stroke differed by regions, with more of metabolic risk in America and Europe, in contrast to high systolic blood pressure in Asian and African regions. GWAS risk loci of stroke and its comorbid conditions indicate distinct population stratification for each of these conditions, signifying for population-specific risk. Unique and shared genetic risk variants for stroke, and its comorbid and followed up with ethnic-specific variation can help in determining regional risk drivers for stroke. Unique ethnic-specific risk variants and their distinct patterns of linkage disequilibrium further uncover the drivers for phenotypic variation. Therefore, identifying population- and comorbidity-specific risk variants might help in defining the threshold for risk, and aid in developing population-specific prevention strategies for stroke.
Background Synaptic dysfunction, characterized by synapse loss and structural alterations, emerges as a prominent correlate of cognitive decline in Alzheimer’s disease (AD). Actin cytoskeleton, which serves as the structural backbone of synaptic architecture, is observed to be lost from synapses in AD. Actin cytoskeleton loss compromises synaptic integrity, affecting glutamatergic receptor levels, neurotransmission, and synaptic strength. Understanding these molecular changes is crucial for developing interventions targeting synaptic dysfunction, potentially mitigating cognitive decline in AD. Methods In this study, we investigated the synaptic actin interactome using mass spectrometry in a mouse model of AD, APP/PS1. Our objective was to explore how alterations in synaptic actin dynamics, particularly the interaction between PSD-95 and actin, contribute to synaptic and cognitive impairment in AD. To assess the impact of restoring F-actin levels on synaptic and cognitive functions in APP/PS1 mice, we administered F-actin stabilizing agent, jasplakinolide. Behavioral deficits in the mice were evaluated using the contextual fear conditioning paradigm. We utilized primary neuronal cultures to study the synaptic levels of AMPA and NMDA receptors and the dynamics of PSD-95 actin association. Furthermore, we analyzed postmortem brain tissue samples from subjects with no cognitive impairment (NCI), mild cognitive impairment (MCI), and Alzheimer’s dementia (AD) to determine the association between PSD-95 and actin. Results We found a significant reduction in PSD-95-actin association in synaptosomes from middle-aged APP/PS1 mice compared to wild-type (WT) mice. Treatment with jasplakinolide, an actin stabilizer, reversed deficits in memory recall, restored PSD-95-actin association, and increased synaptic F-actin levels in APP/PS1 mice. Additionally, actin stabilization led to elevated synaptic levels of AMPA and NMDA receptors, enhanced dendritic spine density, suggesting improved neurotransmission and synaptic strength in primary cortical neurons from APP/PS1 mice. Furthermore, analysis of postmortem human tissue with NCI, MCI and AD subjects revealed disrupted PSD-95-actin interactions, underscoring the clinical relevance of our preclinical studies. Conclusion Our study elucidates disrupted PSD-95 actin interactions across different models, highlighting potential therapeutic targets for AD. Stabilizing F-actin restores synaptic integrity and ameliorates cognitive deficits in APP/PS1 mice, suggesting that targeting synaptic actin regulation could be a promising therapeutic strategy to mitigate cognitive decline in AD.
Simple Summary Forkhead-box M1 (FOXM1) is a proliferation-associated transcription factor, overexpressed in almost all the cancers, making its regulation worth investigating. FOXM1 is known to bind to the promoters of certain microRNAs, a class of biomolecules involved in post-transcriptional gene regulation. Database mining followed by Venn analysis led us to the shortlisting of seven microRNAs, among which microRNA-532-3p showed the strongest interaction with FOXM1 3’UTR. The ectopic overexpression of miR-532-3p in colorectal cancer (CRC) cells led to decreased FOXM1 levels which resulted in the alteration of CRC functionalities. These altered phenotypes were supported by a change in the expression of proliferation and EMT markers. In conclusion, the present study suggested that the regulation of FOXM1 by microRNA-532-3p via its interaction with FOXM1 3’UTR inhibited CRC proliferation, migration, and invasion. Abstract Colorectal cancer (CRC) is a heterogeneous disease and classified into various subtypes, among which transcriptional alterations result in CRC progression, metastasis, and drug resistance. Forkhead-box M1 (FOXM1) is a proliferation-associated transcription factor which is overexpressed in CRC and the mechanisms of FOXM1 regulation have been under investigation. Previously, we showed that FOXM1 binds to promoters of certain microRNAs. Database mining led to several microRNAs that might interact with FOXM1 3’UTR. The interactions between shortlisted microRNAs and FOXM1 3’UTR were quantitated by a dual-luciferase reporter assay. MicroRNA-532-3p interacted with the 3’UTR of the FOXM1 mRNA transcript most efficiently. MicroRNA-532-3p was ectopically overexpressed in colorectal cancer (CRC) cell lines, leading to reduced transcript and protein levels of FOXM1 and cyclin B1, a direct transcriptional target of FOXM1. Further, a clonogenic assay was conducted in overexpressed miR-532-3p CRC cells that revealed a decline in the ability of cells to form colonies and a reduction in migratory and invading potential. These alterations were reinforced at molecular levels by the altered transcript and protein levels of the conventional EMT markers E-cadherin and vimentin. Overall, this study identifies the regulation of FOXM1 by microRNA-532-3p via its interaction with FOXM1 3’UTR, resulting in the suppression of proliferation, migration, and invasion, suggesting its role as a tumor suppressor in CRC.
Hands are in fact the main route of transmission of pathogenic infections. By using proper hand sanitization, we can break the virus’s transmission chain, which is especially important in the ongoing COVID pandemic outbreaks. The effectiveness of hand sanitization is solely dependent on the use of sufficient antibacterial agents, which come in a variety of levels and types, including antimicrobials commercial, water-based, or alcohol-based hand sanitizer, the latter being widely used during pandemics. Therefore, the sudden overuse of sanitizers also could lead to an increase in the tolerance limit for normal hand flora and the new development of antimicrobial resistance (AMR). In this study, we investigated the relationship between hand sanitizer-tolerant bacteria and their antibiotic resistance profile to multiple antibiotic agents. On a timely basis before and after using different hand sanitizers, bacterial strains were collected from the volunteers of CSIR-Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI). Sanitizer tolerant bacterial strains were observed also just after the application of sanitizers, which also showed the AMR phenomenon. The resultant sanitizers’ resistant microbiome showed the dominant presence of Bacillus sp., Staphyloccocus sp., Paenibacillus sp., Lysinibacillus sp., Exiguobacterium sp. and Leclercia sp. All 36 nos of bacterial strains showed MDR (> 5 nos).
The co-evolution of plants and pathogens has enabled them to 'outsmart' each other by promoting their own defense responses and suppressing that of the other. While plants are reliant on their sophisticated immune signalling pathways, pathogens make use of effector proteins to achieve the objective. This entails rapid regulation of the underlying molecular mechanisms for prompt induction of the associated signalling events in both plants as well as pathogens. The last decade has witnessed the emergence of post-translational modification (PTM) of proteins as key players in modulating cellular responses. Their ability to expand the functional diversity of the proteome and induce rapid changes at the appropriate time enables them to play crucial roles in the regulation of plant-pathogen interactions. Therefore, this review will delve into the intricate interplay of five major PTMs in plant defense and pathogen countermeasures. The review discusses how plants employ PTMs to fortify their immune networks, and how pathogen effectors utilize/target host modification systems to gain entry into the plant and cause disease. The review also underscores the need for identification of newer PTMs and proposes to use PTM machineries as potential targets for genome editing approaches.
Author summary Chlamydial infection has a high global prevalence and is a major health concern. Untreated infections may cause complications and lead to serious health problems, especially in women. Although the infection is usually localized to the genital tract, experiments performed in a mouse infection model as well as the accumulating clinical data suggest that the human gastrointestinal (GI) tract might represent a hidden infection niche and a source of reinfections. In our study, we used the advantages of the organoid technology to model the chlamydial infection in patient-derived primary GI epithelial cells. We were able to show that these cells are resistant to the infection, however, Chlamydia could utilize a basolateral entry route for efficient infection. Chlamydia form either normal or persistent-like developmental forms in these GI epithelial cells. We also showed the importance of the plasmid-mediated virulence in the infection of human GI cells. The results obtained in the GI infection model replicated phenotypes predicted and expected for Chlamydia human intestinal infection, and therefore support a role of the human GI tract as a potential niche for chlamydial infection.
Introduction Sorafenib (Sor) is the first-line treatment option in clinics for treating advanced unresectable hepatocellular carcinoma (HCC). However, acquired chemoresistance and adverse side effects associated with Sor monotherapy limit its clinical benefits. We have previously reported the exceptional anti-HCC potential of uttroside B (Utt-B), a furostanol saponin isolated in our lab from Solanum nigrum Linn. leaves. The current study has evaluated the supremacy of a combinatorial regimen of Sor and Utt-B over Sor monotherapy. Methods MTT assay was used for In vitro cytotoxicity studies. A clonogenic assay was conducted to assess the anti-proliferative effect of the combination. Annexin V/PI staining, confocal microscopy, FACS cell cycle analysis, and Western blotting experiments were performed to validate the pro-apoptotic potential of the combination in HepG2 and Huh7 cell lines. Pharmacological safety evaluation was performed in Swiss albino mice. Results Our results indicate that Utt-B augments Sor-induced cytotoxicity in HepG2 and Huh7 cells. The combination inhibits the proliferation of liver cancer cells by inducing apoptosis through activation of the caspases 7 and 3, leading to PARP cleavage. Furthermore, the combination does not induce any acute toxicity in vivo, even at a dose five times that of the effective therapeutic dose. Conclusion Our results highlight the potential of Utt-B as an effective chemosensitizer, which can augment the efficacy of Sor against HCC and circumvent Sor-induced toxic side effects. Moreover, this is the first and only report to date on the chemosensitizing potential of Utt-B and the only report that demonstrates the therapeutic efficacy and pharmacological safety of a novel combinatorial regimen involving Utt-B and Sor for combating HCC.
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426 members
Jackson James
  • Neuro-Stem Cell Biology Lab
Surya Ramachandran
  • Division of Cardiovascular Disease Biology
Krishnankutty Nair Chandrika Sivakumar
  • Distributed Information Sub-Centre (Bioinformatics Centre)
Kuzhuvelil B Harikumar
  • Cancer Research Program
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Thiruvananthapuram, India