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Lung cancer is one of the highly lethal forms of cancer whose incidence has worldwide rapidly increased over the past few decades. About 80-85% of all lung cancer cases constitute non-small cell lung cancer (NSCLC), with adenocarcinoma, squamous cell carcinoma and large cell carcinoma as the main subtypes. Immune checkpoint inhibitors have led to significant advances in the treatment of a variety of solid tumors, significantly improving cancer patient survival rates.The cytotoxic drugs in combination with anti-PD-(L)1 antibodies is a new method that aims to reduce the activation of immunosuppressive and cancer cell prosurvival responses while also improving direct cancer cell death. The most commonly utilized immune checkpoint inhibitors for patients with non-small cell lung cancer are monoclonal antibodies (Atezolizumab, Cemiplimab, Ipilimumab, Pembrolizumab etc.) against PD-1, PD-L1, and CTLA-4. Among them, Atezolizumab (TECENTRIQ) and Cemiplimab (Libtayo) are engineered monoclonal anti programmed death ligand 1 (PD-L1) antibodies that inhibit binding of PD-L1 to PD-1 and B7.1. As a result, T-cell proliferation and cytokine synthesis are inhibited leading to restoring the immune homeostasis to fight cancer cells.In this review article, the path leading to the introduction of immunotherapeutic options in lung cancer treatment is described, with analyzing the benefits and shortages of the current immunotherapeutic drugs. In addition, possibilities to co-administer immunotherapeutic agents with standard cancer treatment modalities are also considered.

Abstract: Colorectal cancer is the second leading cause of cancer deaths worldwide and has engrossed researchers' attention toward its detection and prevention at early stages. Primarily associated with genetic and environmental risk factors, the disease has also shown its emergence due to dysbiosis in microbiota. The microbiota not only plays a role in modulating the metabolisms of metastatic tissue but also has a keen role in cancer therapy. The immune cells are responsible for secreting various chemokines and cytokines, and activating pattern recognition receptors by different microbes can lead to the trail by which these cells regulate cancer. Furthermore, mixed immune reactions involving NK cells, tumor-associated macrophages, and lymphocytes have shown their connection with the microbial counterpart of the disease. The microbes like Bacteroides fragilis, Fusobacterium nucleatum, and Enterococcus faecalis and their metabolites have engendered inflammatory reactions in the tumor microenvironment. Hence the interplay between immune cells and various microbes is utilized to study the changing metastasis stage. Targeting either immune cells or microbiota could not serve as a key to tackling this deadly disorder. However, harnessing their complementation towards the disease can be a powerful weapon for developing therapy and diagnostic/prognostic markers. In this review, we have discussed various immune reactions and microbiome interplay in CRC, intending to evaluate the effectiveness of chemotherapy and immunotherapy and their parallel relationship.

Combating triple-negative breast cancer (TNBC) is still a problem, despite the development of numerous drug delivery approaches. Mucin1 (MUC1), a glycoprotein linked to chemo-resistance and progressive malignancy, is unregulated in TNBC. GO-201, a MUC1 peptide inhibitor that impairs MUC1 activity, promotes necrotic cell death by binding to the MUC1-C unit. The current study deals with the synthesis and development of a novel nano-formulation (DM-PEG-PCL NPs) comprising of polyethylene glycol-polycaprolactone (PEG-PCL) polymer loaded with MUC1 inhibitor and an effective anticancer drug, doxorubicin (DOX). The DOX and MUC1 loaded nanoparticles were fully characterized, and their different physicochemical properties, viz. size, shape, surface charge, entrapment efficiencies, release behavior, etc., were determined. With IC50 values of 5.8 and 2.4 nm on breast cancer cell lines, accordingly, and a combination index (CI) of Further, DM-PEG-PCL NPs treated breast cancer cells showed increased mitochondrial damage with enhancement in caspase-3 expression and reduction in Bcl-2 expression.In vivo evaluation using Ehrlich Ascites Carcinoma bearing mice explicitly stated that DM-PEG-PCL NPs therapy minimized tumor growth relative to control treatment. Further, acute toxicity studies did not reveal any adverse effects on organs and their functions, as no mortalities were observed.The current research reports for the first time the synergistic approach of combination entrapment of a clinical chemotherapeutic (DOX) and an anticancer peptide (MUC1 inhibitor) encased in a diblock PEG-PCL copolymer. Incorporating both DOX and MUC1 inhibitors in PEG-PCL NPs in the designed nanoformulation has provided chances and insights for treating triple-negative breast tumors. Our controlled delivery technology is biodegradable, non-toxic, and anti-multidrug-resistant. In addition, this tailored smart nanoformulation has been particularly effective in the therapy of triple-negative breast cancer.

The interaction between gut microbes and gastrointestinal (GI) tract carcinogenesis has always attracted researchers' attention to identify therapeutic targets or potential prognostic biomarkers. Various studies have suggested that the microbiota do show inflammation and immune dysregulation, which led to carcinogenesis in GI tract. In this review, we have focused on the role of microbes present in the gut, intestine, or faeces in GI tract cancers, including esophageal cancer, gastric cancer, and colorectal cancer. Herein, we have discussed the importance of the microbes and their metabolites, which could serve as diagnostic biomarkers for cancer detection, especially in the early stage, and prognostic markers. To maximize the effect of the treatment strategies, an accurate evaluation of the prognosis is imperative for clinicians. There is a vast difference in the microbiota profiles within a population and across the populations depending upon age, diet, lifestyle, genetic makeup, use of antibiotics, and environmental factors. Therefore, the diagnostic efficiency of the microbial markers needs to be further validated. A deeper understanding of the GI cancer and the host microbiota is needed to acquire pivotal information about disease status.

Influenza viruses cause acute respiratory illnesses in birds, humans, and other mammals, and are a major public health concern around the world. Pandemic flu could be caused by an unforeseen human adaptation of an influenza subtype or strain rather than currently circulating influenza viruses. The need for plant metabolites-based new anti-influenza drugs appears to be urgent. Blocking Haemeagglutinin (HA) protein is one of the most appealing drug targets to halt the growth of the virus. The influenza virus can acquire resistance to currently existing therapies, therefore necessitating the development of new medications. The plant's bioactive metabolites, flavanoids are having potential medicinal efficacy. The current study aimed to identify certain flavonoids (Diosmetin, Tangeritin, and Anthocyanidins) that might interact with the HA protein of the influenza virus and help in inhibiting its growth. We used PyRx v0.8 for virtual screening and docking studies. The highest binding affinity docked structures were analyzed using PyMOL and Discovery Studio Visualizer. The present study revealed that these naturally occurring compounds interacted with HA protein, resulting in the minimization of energy in the range of -5.2 to -7.0 kcal/mol. Diosmetin showed the best binding affinity of -7.0Kcal/mol. The molecular binding studies revealed that Diosmetin, Tangeritin, and Anthocyanidins are potential compounds to test against HA protein and can be used to develop effective anti-influenza agents.

Abstract: The second most pervasive cancer affecting the survival of women across the world is breast cancer. One of the biggest challenges in breast cancer treatment is the chemoresistance of cancer cells to various medications after some time. Therefore, highly specific blood-based biomarkers are required for early breast cancer diagnosis to overcome chemoresistance and improve patient survival. These days, exosomal miRNAs have attracted much attention as early diagnostic blood-based biomarkers because of their high stability, secretion from malignant tumor cells, and excellent specificity for different breast cancer subtypes. In addition, exosomal miRNAs regulate cell proliferation, invasion, metastasis, and apoptosis by binding to the 3′UTR of their target genes and limiting their production. This review focuses on the functions of exosomal miRNAs in tumorigenesis via targeting multiple signaling pathways as well as chemosensitivity and resistance mechanisms. In addition, the growing pieces of evidence discussed in this review suggest that circulating exosomal miRNAs could be utilized as potential next-generation therapeutic target vehicles in the treatment of breast cancer.

Biogenic nanoparticles (NPs) derived from microbes present an excellent opportunity to deal with various challenges in medicine, diagnosis, environment and agriculture. In the area of agriculture sciences, researchers are facing challenges related to excessive utilization of pesticides which can be answered by utilizing plant growth-promoting (PGP) microbes. Herein, we have employed the culture filtrate of two PBP bacteria strains, Serratia marcescens and Burkholderia cepacia to prepare biogenic silver NPs. The biogenic silver NPs were characterized by various techniques viz. UV-VIS spectroscopy, SEM, XRD and FTIR. The biogenic AgNPs were able to control the growth of phytopathogenic fungi Aspergillus niger, A. fumigatus, Fusarium oxysporum, Pythium sp., and Rosellinia sp. by more than 80% as examined by in vitro growth reduction on agar medium. Very significantly, the growth inhibition of seedlings by phytopathogenic fungi was efficiently rescued using biogenic AgNPs derived from PGP bacteria. These results indicate the potential use of biogenic NPs to reduce the burden of chemical-based pesticides.

Objectives The study was aimed to evaluate the potential of hydroalcoholic extract of Pinus roxburghii (PRE) stem bark in post-menopausal osteoporosis and its underlying mechanisms. Methods In silico docking of the markers was done using AutoDock version 4.2. for molecular targets: receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG) and Cathepsin. Female Wistar rats of bodyweight 200–250 g were employed and surgical ovariectomy (OVX) was performed. PRE was administered at a dose of 100 and 200 mg/kg whereas standard drug, raloxifene given at 1 mg/kg orally for eight weeks. Key findings PRE (20 and 40 µg/mL) significantly increased the cellular proliferation in osteoblastic UMR cell lines 11.58 and 15.09% respectively. Eight weeks after surgical removal of ovaries, a significant bone porosity was confirmed by modulation in bone breaking strength of tibia, lumber, and femur; bone mineral density (BMD), calcium, phosphorus, hydroxyproline levels in OVX group. Treatment with PRE 100 and 200 mg/kg significantly restored the bone loss. Real-time polymerase chain reaction (RT-PCR) analysis of molecular markers RANK, OPG and cathepsin and histology also confirmed the attenuation of bone loss. The quantification of quercetin, gallic acid, caffeic acid, catechin, tannic acid and ascorbic acid was done by high-performance liquid chromatography (HPLC) and high performance thin layer chromatography. Conclusions P. roxburghii produced anti-osteoporotic effect possibly due to estrogenic modulation, and improved bone remodeling.

Cancer immunotherapy utilizes the immune system and its wide-ranging components to deliver anti-tumor responses. In immune escape mechanisms, tumor microenvironment-associated soluble factors and cell surface-bound molecules are mainly accountable for the dysfunctional activity of tumor-specific CD8

In the current work, we have doped g-C3N4 (GCN), a conjugated polymer based on heptazine-group with phosphorous and synthesized phosphorous doped g-C3N4 (PCN) has been coupled with CNT to enhance its photodegradation activity. Herein, CNT/PCN nanocomposites (having different CNT wt% i.e. 0.01, 0.02 and 0.03) were successfully fabricated via straight forward sonochemical method while GCN and PCN were prepared through direct thermal polycondensation method for Imidacloprid (IMI) pesticide degradation. Photodegradation activity of nanocomposite was enormously affected by doping but more significantly by nature of CNT content and addition of H2O2. EIS and PL analysis confirmed enhanced photogenerated charge carriers separation in CNT/PCN nanocomposite than GCN and PCN. Through BET analysis increase in surface area (SBET) of CNT/PCN nanocomposite was observed than PCN (2.8401 m2 g − 1 to 14.0294 m2 g − 1). Photodegradation processes follow pseudo-first order kinetics as R2 values were attained between 0.95–0.98. Synthesized 0.02 wt% CNT/PCN and 0.02 wt% CNT/PCN/H2O2 nanocomposite (without H2O2 and with H2O2) exhibited superior IMI photodegradation efficiency i.e. 93% and 97% respectively, than other photocatalysts (GCN, PCN, 0.01 wt% CNT/PCN, 0.03 wt% CNT/PCN, GCN/H2O2, PCN/H2O2, 0.01 wt% CNT/PCN/H2O2, 0.03 wt% CNT/PCN/H2O2) after visible light illumination. The most Plausible photocatalytic mechanism was also illustrated stipulating significance of h+, •O2−reactive species for CNT/PCN nanocomposite and •OH radicals for CNT/PCN/H2O2 nanocomposite in photodegradation process. Furthermore, antimicrobial and cytotoxic studies revealed that CNT/PCN confers antibacterial activity but do not cause harm to normal human cells.

Ferroptosis has been characterized over the last few years as a form of iron-dependent regulated cell death which is accompanied by an accumulation of reactive oxygen species and lipid oxidation products inside the cells along with typical morphological alterations in mitochondria. Ferroptosis is inhibited by specific inhibitors called ferrostatin-1 and liproxstatin-1, apart from iron-chelators and several antioxidants, and the process is implicated in multiple pathological conditions. There are, however, certain ambiguities about ferroptosis, especially with regard to the involvement of mitochondria in the final execution of ferroptotic death. This study uses two typical inducers of ferroptosis such as erastin and ferric ammonium citrate on SH-SY5Y cells, and shows clearly that ferroptotic death of cells is accompanied by the loss of mitochondrial membrane potential and intracellular ATP content along with an accumulation of reactive oxygen species and malondialdehyde as well as a depletion of reduced glutathione. All these are prevented by ferrostatin-1 and liproxstatin-1. Additionally, cyclosporine A prevents mitochondrial alterations and cell death induced by erastin or ferric ammonium citrate, implying the crucial role of mitochondrial permeability transition pore activation in ferroptotic death. Under our experimental conditions, it is also observed that the late-phase production of reactive oxygen species is inhibited by cyclosporine A.

Parkinson's disease (PD) is a neurodegenerative disorder characterized classically by motor manifestations. However, nonmotor symptoms appear early in the course of the disease progression, making both diagnosis and treatment difficult. The pathology of PD is complicated by the accumulation and aggregation of misfolded proteins in intracellular cytoplasmic inclusions called Lewy bodies (LBs). The main toxic component of LBs is the protein α-Synuclein which plays a pivotal role in PD pathogenesis. α-Synuclein can propagate from cell-to-cell exhibiting prion-like properties and spread PD pathology throughout the central nervous system. Immunotherapeutic interventions in PD, both active and passive immunization, have targeted α-Synuclein in both experimental models and clinical trials. In addition, targeting the hyperactive inflammation in PD also holds promise in designing potential immunotherapeutics. The inflammatory and proteotoxic pathways are interlinked and contribute immensely to the disease pathology. In this chapter, we critically review the targets of immunotherapeutic interventions in PD, focusing on the pathogenetic mechanisms of PD, particularly neuroinflammation and α-Synuclein misfolding, aggregation, and propagation. We thoroughly summarized the various immunotherapeutic strategies designed to treat PD-in vitro, in vivo, and clinical trials. The development of these targeted immunotherapies could open a new avenue in the treatment of patients with PD.

To match the current life-style, there is a huge demand and market for the processed food whose manufacturing requires multiple steps. The mounting demand increases the pressure on the producers and the regulatory bodies to provide sensitive, facile, and cost-effective methods to safeguard consumers’ health. In the multistep process of food processing, there are several chances that the food-spoiling microbes or contaminants could enter the supply chain. In this contest, there is a dire necessity to comprehend, implement, and monitor the levels of contaminants by utilizing various available methods, such as single-cell droplet microfluidic system, DNA biosensor, nanobiosensor, smartphone-based biosensor, aptasensor, and DNA microarray-based methods. The current review focuses on the advancements in these methods for the detection of food-borne contaminants and pathogens.

Plant growth promoting microbes impact the life of trees, shrubs and other plant species in the forest. Fire in forest adversely affects the growth of plants directly by burning and heat stress and indirectly by affecting the survival of plant growth promoting microbes. Herein, we analyzed changes in the population of cultivable microbes owing to fire in the pine grown forest in the Indian Himalayan region. We found that soil in the burnt region predominantly harbored Gram-positive bacteria which lacked biofertilizer and biocontrol traits. Forest fire resulted in the loss of Gram-negative strains of genera Pseudomonas, Serratia, Enterobacter, Burkholderia, Klebsiella, and Pantoea. Similarly, we found that the rhizospheric region of grasses which came after the event of the fire in the pine forest lacked the beneficial Gram-negative strains. Furthermore, in plantae experiments in which pea (Pisum sativum) and wheat (Triticum aestivum) seedlings were treated with bacteria isolated from the burnt and unburnt forest bed showed that bacteria from the burnt region did not affect the growth of seedlings as compared to the bacteria isolated from the unburnt region which improved the growth of seedlings. Comparing the soil parameters between burnt and unburnt region showed a decrease in nutrients, and, increase in both bulk density and dispersion ratio due to the forest fire. Our results strongly indicate that forest fire reduces the population of cultivable beneficial microbes and this loss could have a negative impact on the growth of forest flora.

In the original publication [...]

Parkinson’s disease (PD) is the second most common neurodegenerative disorder of the elderly, presenting primarily with symptoms of motor impairment. The disease is diagnosed most commonly by clinical examination with a great degree of accuracy in specialized centers. However, in some cases, non-classical presentations occur when it may be difficult to distinguish the disease from other types of degenerative or non-degenerative movement disorders with overlapping symptoms. The diagnostic difficulty may also arise in patients at the early stage of PD. Thus, a biomarker could help clinicians circumvent such problems and help them monitor the improvement in disease pathology during anti-parkinsonian drug trials. This review first provides a brief overview of PD, emphasizing, in the process, the important role of α-synuclein in the pathogenesis of the disease. Various attempts made by the researchers to develop imaging, genetic, and various biochemical biomarkers for PD are then briefly reviewed to point out the absence of a definitive biomarker for this disorder. In view of the overwhelming importance of α-synuclein in the pathogenesis, a detailed analysis is then made of various studies to establish the biomarker potential of this protein in PD; these studies measured total α-synuclein, oligomeric, and post-translationally modified forms of α-synuclein in cerebrospinal fluid, blood (plasma, serum, erythrocytes, and circulating neuron-specific extracellular vesicles) and saliva in combination with certain other proteins. Multiple studies also examined the accumulation of α-synuclein in various forms in PD in the neural elements in the gut, submandibular glands, skin, and the retina. The measurements of the levels of certain forms of α-synuclein in some of these body fluids or their components or peripheral tissues hold a significant promise in establishing α-synuclein as a definitive biomarker for PD. However, many methodological issues related to detection and quantification of α-synuclein have to be resolved, and larger cross-sectional and follow-up studies with controls and patients of PD, parkinsonian disorders, and non-parkinsonian movement disorders are to be undertaken.

Around 2200 miRNA (microRNA) genes were found in the human genome. miRNAs are arranged in clusters within the genome and share the same transcriptional regulatory units. It has been revealed that approximately 50% of miRNAs elucidated in the genome are transcribed from non-protein-coding genes, and the leftover miRNAs are present in the introns of coding sequences. We are now approaching a stage in which miRNA diagnostics and therapies can be established confidently, and several commercial efforts are underway to carry these innovations from the bench to the clinic. MiRNAs control many of the significant cellular activities such as production, differentiation, growth, and metabolism. Particularly in the immune system, miRNAs have emerged as a crucial biological component during diseased state and homeostasis. miRNAs have been found to regulate inflammatory responses and autoimmune disorders. Moreover, each miRNA targets multiple genes simultaneously, making miRNAs promising tools as diagnostic biomarkers and as remedial targets. Still, one of the major obstacles in miRNA-based approaches is the achievement of specific and efficient systemic delivery of miRNAs. To overcome these challenges, nanoformulations have been synthesized to protect miRNAs from degradation and enhance cellular uptake. The current review deals with the miRNA-mediated regulation of the recruitment and activation of immune cells, especially in the tumor microenvironment, viral infection, inflammation, and autoimmunity. The nano-based miRNA delivery modes are also discussed here, especially in the context of immune modulation.

Stephania glabra is a wild medicinal plant possessing multiple uses as anti-cancer, antimicrobial and antioxidant activities. Different extracts and fractions were prepared from S. glabra tubers and were analyzed for different activities. Evaluation of the total phenolic and flavonoid content revealed that chloroform extract of S. glabra contain maximum phenolic content and maximum flavonoid content was found in methanolic extract. Dry powder analysis of the tubers revealed the presence of saponins, alkaloids and proteins. Ethyl acetate extract of S. glabra tubers showed highest antioxidant potential as revealed by ABTS radical scavenging activity. Methanolic extract has the highest anti-cancer activity while chloroform extracts and fractions have highest antimicrobial activity. These activities can be attributed to the high amount of the phytoconstituents present in these extracts

The development of neuroprotective drugs targeting mitochondria could be an important strategy in combating the progressive clinical course of Parkinson's disease. In the current study, we demonstrated that in SH-SY5Y cells (human dopaminergic neuroblastoma cell line), rotenone caused a dose-dependent (0.25-1 μM) and time-dependent (up to 48 h) loss of cell viability and a loss of cellular ATP content with mitochondrial membrane depolarization and an increased formation of reactive oxygen species; all these processes were markedly prevented by the mitochondrial permeability transition pore blocker cyclosporine A, which did not affect complex I inhibition by rotenone. The nuclear morphology of rotenone-treated cells for 48 h indicated the presence of both necrosis and apoptosis. We then examined the effects of cyclosporine A on the rotenone-induced model of Parkinson's disease in Wistar rats. Cyclosporine A significantly improved the motor deficits and prevented the loss of nigral dopaminergic neurons projecting into the striatum in rotenone-treated rats. Being a marketed immuno-suppressive drug, cyclosporine A should be further evaluated for its putative neuroprotective action in Parkinson's disease.

Current modern dietary patterns throughout the world have resulted in adverse health implications. On the other hand, current agricultural practices and methods employed in food industries lead to the exploitation of the environment and generate nutrient-rich waste, which is underutilized. The simple answer to both these problems could be the adoption of fermentation technology. Due to the presence of functional microorganisms, fermented foods possess unique properties like probiotics properties, antimicrobial, antioxidant, peptide production, etc., imparting health benefits to consumers. Moreover, agricultural and food processing waste fermentation could generate value-added healthy foods and sustainable food sources. Not only this, fermented food products can be an essential source of generating livelihoods by producing necessary food ingredients through fermentation of commonly generated organic wastes in rural areas and encouraging and promoting traditional fermented recipes that are also healthy. This review discusses how reviving and promoting food fermentation technology can help reduce these two problems related to health and sustainability. Furthermore, the role of lactic acid bacteria and fungi like yeast, Penicillium, Acetobacter etc., in producing beneficial metabolites and their impact on controlling various lifestyle disorders and aging have been discussed. In addition, fermented foods also enrich gut microbiota, which imparts health benefits.

Our study aimed to develop and find out the best drug candidate against the mechanistic target of rapamycin (mTOR/FRB) domain having a critical role in the aetiology of breast cancer. The FKBP12-rapamycin-binding (FRB) domain in the essential phosphoinositide 3 kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway has been a vital player in the disease progression in breast cancer. By using structure-based drug designing , the best possible targets have been identified and developed. The three-dimensional structure of the target protein was generated using I-TASSER. The ligands were generated against the most suitable target active site using standard tools for active site identification. Furthermore, the seed molecule was drawn using Chemsketch, which was then grown into the pocket using Ligbuilder. The obtained ligands were further validated using online programs for bioavailability and toxicity, followed by molecular dynamic simulations. The study concludes that the equilibrated NVT-NPT complexes indicate LIG2 stability over LIG3. RMSD and RMSF have shown that the complex of LIG2 is more stable than LIG3. LIG2 has the potential antagonistic properties to target the mTOR/FRB domain and has therapeutic implications for breast cancer.

Background: Pinus roxburghii has been used in the Himalayan region as folkloric remedy while nothing is yet known about its immunomodulatory potential. Methods: The crude extracts of green and fallen pine needles were subjected to sequential fractionation to get partially purified fractions. Human peripheral blood lymphocytes (PBL) were used to analyze immunoenhancing potential of these fractions. Microcytotoxicity assay was employed to investigate improved cancer cells killing capabilities of PBL against various cancer cell lines. GC-MS was carried out to identify the major compounds in the bioactive fractions. Results: The lymphocyte proliferation assay depicted the immunoenhancing potential of extracts and fractions of fallen and green needles of P. roxburghii. The ethyl acetate fractions of both fallen and green needles displayed highest mitogenic activity on human PBL. Both fractions heightened the expression of cell surface markers (CD3, CD8, and CD56) and significantly increased the production of cytokines (IL-2, IFN-γ and TNF-α). The enhanced intracellular granulysin (immunomarker for activated CTLs and NK cells) expression also confirmed immune stimulatory potential of these fractions on human lymphocytes. The ethyl acetate fractions of pine needles enhanced the cytotoxicity of PBL towards various cancer cells (HCT-116, HeLa, PC-3 and A549) as compared to untreated PBL. GC-MS analysis showed presence of major compounds like 3-α-mannobiose, octakis (trimethylsilyl) ether, methyloxime in ethyl acetate fraction of the green needles and cyclodecasiloxane, eicosamethyl in ethyl acetate fraction of the fallen needles. Conclusion: The bioactive fractions of the fallen and green needles of P. roxburghii stimulate cancer cells killing potential of human lymphocytes.

Rhamnolipids (RLs) are surface-active compounds and belong to the class of glycolipid biosurfactants, mainly produced from Pseudomonas aeruginosa. Due to their non-toxicity, high biodegradability, low surface tension and minimum inhibitory concentration values, they have gained attention in various sectors like food, healthcare, pharmaceutical and petrochemicals. The ecofriendly biological properties of rhamnolipids make them potent materials to be used in therapeutic applications. RLs are also known to induce apoptosis and thus, able to inhibit proliferation of cancer cells. RLs can also act as immunomodulators to regulate the humoral and cellular immune systems. Regarding their antimicrobial property, they lower the surface hydrophobicity, destruct the cytoplasmic membrane and lower the critical micelle concentration to kill the bacterial cells either alone or in combination with nisin possibly due to their role in modulating outer membrane protein. RLs are also involved in the synthesis of nanoparticles for in vivo drug delivery. In relation to economic benefits, the post-harvest decay of food can be decreased by RLs because they prevent the mycelium growth, spore germination of fungi and inhibit the emergence of biofilm formation on food. The present review focuses on the potential uses of RLs in cosmetic, pharmaceutical, food and health-care industries as the potent therapeutic agents.

Background Datura stramonium L. is widely used across the world for its therapeutic potential to treat inflammatory disorders. The current work was designed to isolate and identify steroidal lactones from D. stramonium leaves and evaluate their anti-inflammatory and analgesic properties. Methods Several compounds were isolated from D. stramonium leaves and characterized by nuclear magnetic resonance and high-resonance electron spray ionization mass spectrometry techniques. Further, anti-inflammatory properties of these compounds were evaluated by in vitro assays, such as release of NO and pro-inflammatory cytokines by lipopolysaccharide (LPS)-activated J774A.1 macrophages. Using in vivo models, anti-inflammatory and analgesic effects were examined by mouse tail-flick, carrageenan-induced inflammation in rat paw model, vascular permeability in rats, and acetic acid-induced writhing in mice. The docking studies were performed for assessing the binding efficiency of the test compounds with cyclooxygenase-1 (COX-1) and COX-2, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), inducible nitric oxide synthases (iNOS) and nuclear factor-κB (NF-κB). Results Three lactones were isolated and confirmed as daturalactone (D1), 12-deoxywithastramonolide (D23), and daturilin (D27). Further, the isolated compounds showed nitric oxide inhibition and pro-inflammatory cytokines released by LPS-activated J774A.1 macrophages. The in vivo results suggest that D1, D23 and D27 (20 mg/kg) were able to reduce the pain and inflammation in various animal models. The docking analysis showed that these three compounds actively bind with COX-1, COX-2, LOX-1, NF-κB, and iNOS, validating the anti-inflammatory effects of the lactones. Conclusion These findings demonstrate substantial anti-inflammatory and analgesic properties of D. stramonium-derived lactones and their potential as anti-inflammatory agents to treat chronic inflammatory ailments.

Carbon quantum dots are zero-dimensional carbon nanomaterials having a size of less than 10 nm with sp2-/sp3-hybridized carbon atom containing a variety of functional groups at basal plane and periphery. Carbon quantum dots are a new class of carbonaceous material which are recently developed and attracted appreciable importance due to their superlative properties and significant applications in different fields. By virtue of their unique optical, electronic, and efficient light harvesting, tunable photoluminescence, and up-conversion property, carbon quantum dots displayed huge applications in bio-sensing, bio-imaging, drug delivery, photocatalysis, photovoltaics and optoelectronics. Today, contamination of water is one of the biggest and most alarming problems that demands an immediate solution, and non-availability of economical method for water treatment makes it more significant. The potential pollutants of water pollution are heavy metal ions, sewage, pesticide, pharmaceutical waste, and industrial waste. The most abundant carbon as photocatalytic nanomaterial could be a better choice among previously reported conventional photocatalyst and quantum dots.

The current study deals with the investigation of the antioxidant, anti-inflammatory and immunomodulatory properties of the essential oil from Datura stramonium leaves (D. oil). The GC-MS analysis showed that the dominant compounds present in the D. oil were neophytadiene (Phytol acetate) (10.76%), β-damascenone (9.67%), and β- eudesmol (7.2%). D. oil exhibited in vitro scavenging potential of free radicals by DPPH and ABTS assays (IC(50) values 71.35 ±1.06 μg/ml and 61.01 ± 1.07 μg/ml, respectively). We found that D. oil decreased the nitric oxide production in LPS-stimulated J774A.1 cells by 52.43% without affecting their cell viability. D. oil was found to stimulate the proliferation of human peripheral blood mononuclear cells (PBMC) and, also enhanced the secretion of IL-2, IFN-γ and TNF-α. Furthermore, D. oil treatment of PBMC induced the expression of CD3, CD8, and CD56 and intracellular granulysin levels in the immune cells. The treatment of human lymphocytes by D. oil enhanced their ability to kill colon cancer cells HCT-116 (51.09 ± 7.5%) and SW620 (48.57 ± 8.08%) at 20:1 (effector: target ratio). Moreover, these activated lymphocytes cause target cell death by reactive oxygen species and by damaging mitochondrial membrane potential of these cells. Taken together, the current findings showed D. oil as immunotherapeutic agent which can be used for colon cancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13205-020-02438-4) contains supplementary material, which is available to authorized users.

Peroxiredoxins (Prxs) are antioxidant proteins that are involved in cellular defence against reactive oxygen species and reactive nitrogen species. Humans have six peroxiredoxins, hPrxI-VI, out of which hPrxI and hPrxII belongs to the typical 2-Cys class sharing 90% conservation in their amino acid sequence including catalytic residues required to carry out their peroxidase and chaperone activities. Despite the high conservation between hPrxI and hPrxII, hPrxI behaves differently from hPrxII in its peroxidase and chaperone activity. We recently showed in yeast that in the absence of Tsa1 and Tsa2 (orthologs of hPrx) hPrxI protects the cells against different stressors whereas hPrxII does not. To understand this difference, we expressed catalytic mutants of hPrxI in yeast cells lacking the orthologs of hPrxI/II. We found that the catalytic mutants lacking peroxidase function including hPrxIC52S, hPrxIC173S, hPrxIT49A, hPrxIP45A and hPrxIR128A were not able to grow on media with nitrosative stressor (sodium nitroprusside) and unable to withstand heat stress, but surprisingly they were able to grow on an oxidative stressor (H2O2). Interestingly, we found that hPrxI increases the expression of antioxidant genes, GPX1 and SOD1, and this is also seen in the case of a catalytic mutant, indicating hPrxI can indirectly reduce oxidative stress independently of its own peroxidase function and thus suggesting a novel role of hPrxI in altering the expression of other antioxidant genes. Furthermore, hPrxIC83T was resistant to hyperoxidation and formation of stable high molecular weight oligomers, which is suggestive of impaired chaperone activity. Our results suggest that the catalytic residues of hPrxI are essential to counter the nitrosative stress whereas Cys83 in hPrxI plays a critical role in hyperoxidation of hPrxI., Graphical abstract Image 1

Dyslipidaemia has a prominent role in the onset of notorious atherosclerosis, a disease of medium to large arteries. Atherosclerosis is the prime root of cardiovascular events contributing to the most considerable number of morbidity and mortality worldwide. Factors like cellular senescence, genetics, clonal haematopoiesis, sedentary lifestyle-induced obesity, or diabetes mellitus upsurge the tendency of atherosclerosis and are foremost pioneers to definitive transience. Accumulation of oxidized low-density lipoproteins (Ox-LDLs) in the tunica intima triggers the onset of this disease. In the later period of progression, the build-up plaques rupture ensuing thrombosis (completely blocking the blood flow), causing myocardial infarction, stroke, and heart attack, all of which are common atherosclerotic cardiovascular events today. The underlying mechanism is very well elucidated in literature but the therapeutic measures remains to be unleashed. Researchers tussle to demonstrate a clear understanding of treating mechanisms. A century of research suggests that lowering LDL, statin-mediated treatment, HDL, and lipid-profile management should be of prime interest to retard atherosclerosis-induced deaths. We shall brief the Ox-LDL-induced atherogenic mechanism and the treating measures in line to impede the development and progression of atherosclerosis.

Conservative remedies have a gray history worldwide and these provide productive and pertinent tools to tackle ailments. Also, the high altitude areas of Indian Himalayas with their wealthy biodiversity anchorage around 2000 plant species. Ensuing study demonstrates the synthesis of Silver (Ag) and gold (Au) nanoparticles (NPs) and utilizes one of the medicaments Curcuma longa of Indian Himalayas collected from different altitudes. For the same, turmeric rhizome extracts have been prepared from the aforesaid medicament and its anticancer activity and antimicrobial potential have been evaluated. Formation of Ag and Au nanoparticles was realized via UV–Vis spectroscopy and transmission electron microscope (TEM) confirmed size of the NPs. Antibacterial activity has been checked against Bacillus subtilis and Escherichia coli. The anticancer prospective has been observed against A549 and PC3 cell lines of both Au and Ag NPs and the cytotoxicity on PC3 and A549 cell lines was assessed using MTT assay. Results revealed higher amount of biochemicals, antibacterial and anticancer activity in Ag and Au NPs synthesized from rhizome extract collected from highest altitude. For the first time impact of altitudinal variations on phytochemicals and nanoparticles has been reported which have significant effect on its antimicrobial and anticancerous activity.

Despite decades of exhaustive research on cancer, questions about cancer initiation, development, recurrence, and metastasis have still not been completely answered. One of the reasons is the plethora of factors acting simultaneously in a tumour microenvironment, of which not all have garnered attention. One such factor that has long remained understudied and has only recently received due attention is the host microbiota. Our sheer-sized microbiota exists in a state of symbiosis with the body and exerts significant impact on our body’s physiology, ranging from immune-system development and regulation to neurological and cognitive development. The presence of our microbiota is integral to our development, but a change in its composition (microbiota dysbiosis) can often lead to adverse effects, increasing the propensity of serious diseases like cancers. In the present review, we discuss environmental and genetic factors that cause changes in microbiota composition, disposing of the host towards cancer, and the molecular mechanisms (such as β-catenin signalling) and biochemical pathways (like the generation of oncogenic metabolites like N-nitrosamines and hydrogen sulphide) that the microbiota uses to initiate or accelerate cancers, with emphasis on gastrointestinal cancers. Moreover, we discuss how microbiota can adversely influence the success of colorectal-cancer chemotherapy, and its role in tumour metastasis. We also attempted to resolve conflicting results obtained for the butyrate effect on tumour suppression in the colon, often referred to as the ‘butyrate paradox’. In addition, we suggest the development of microbiota-based biomarkers for early cancer diagnosis, and a few target molecules of which the inhibition can increase the overall chances of cancer cure.

A viable electrochemical approach for the detection of dopamine (DA) in uric acid (UA) utilizing a silver nanoparticle-doped 2-aminodiphenylamine (AgNPs-2ADPA) electrode was invented. The electrochemical performance of DA showed that the incorporated electrode displayed outstanding electrocatalytic performance to the electrochemical oxidation of DA. In our study, the AgNPs-2ADPA exhibits remarkable catalytic activity, retaining high current value and resilience when employed as a working electrode component for electrocatalytic detection of DA. We have also utilized the bare and polymeric-2ADPA in DA detection for a comparison study. This method offers a facile route with extraordinary sensitivity, selectivity, and strength for the voltammetric detection of DA, even in the presence of UA and ascorbic acid (AA) as interferents, that can be employed for pharmaceutical and biological specimens.

Conventionally utilized physical and chemical routes for constructing nanoparticles are not eco-friendly. They are associated with many shortcomings like the requirement of specially designed equipment, templates, extremely high temperature, and pressure. Biosynthesis seems to be drawn unequivocal attention owing to its upsurge of applications in different fields like; energy, nutrition, pharmaceutical, and medicinal sciences. To harness the biological sources, the present review describes an environment-friendly route to generate biogenic nanoparticles from the natural plant extracts and the followed mechanisms for their synthesis, growth, and stabilization. The present review summarizes the recent trends involved in the photosynthesis of metallic nanoparticles and their effective use in controlling malaria, hepatitis, cancer, like various endemic diseases. Also, various characterization approaches, such as UV-visible spectrophotometry, Fourier transform infrared spectroscopy, powder X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and energy-dispersive X-ray spectroscopy, are discussed here examine the properties of as-fabricated nanoparticles. Various plant parts like leaves, stems, barks, fruit, and flowers are rich in flavonoids, phenols, steroids, terpenoids, enzymes, and alkaloids, thereby playing an essential role in reducing metal ions that generate metallic nanoparticles. Herein, the uniqueness of phytofabricated nanoparticles along with their distinctive antibacterial, antioxidant, cytotoxic, and drug delivery properties are featured. Lastly, this work highlights the various challenges and future perspectives to further synthesize biogenic metal nanoparticles toward environmental and pharmaceutical advances in the coming years.