Understanding gut microbiome-based machine learning platforms: A review on therapeutic approaches using deep learning.

Human beings possess trillions of microbial cells in a symbiotic relationship. This relationship benefits both partners for a long time. The gut microbiota helps in many bodily functions from harvesting energy from digested food to strengthening biochemical barriers of the gut and intestine. But the changes in microbiota composition and bacteria that can enter the gastrointestinal tract can cause infection. Several approaches like culture-independent techniques such as high-throughput and meta-omics projects targeting 16S ribosomal RNA (rRNA) sequencing are popular methods to investigate the composition of the human gastrointestinal tract microbiota and taxonomically characterizing microbial communities. The microbiota conformation and diversity should be provided by whole-genome shotgun metagenomic sequencing of site-specific community DNA associating genome mapping, gene inventory, and metabolic remodelling and reformation, to ease the functional study of human microbiota. Preliminary examination of the therapeutic potency for dysbiosis-associated diseases permits investigation of pharmacokinetic-pharmacodynamic changes in microbial communities for escalation of treatment and dosage plan. Gut microbiome study is an integration of metagenomics which has influenced the field in the last two decades. And the incorporation of artificial intelligence and deep learning through "omics-based" methods and microfluidic evaluation enhanced the capability of identification of thousands of microbes.

Engineered Nanomaterials for Immunomodulation: A Review.

The immune system usually provides a defense against invading pathogenic microorganisms and any other particulate contaminants. Nonetheless, it has been recently reported that nanomaterials can evade the immune system and modulate immunological responses due to their unique physicochemical characteristics. Consequently, nanomaterial-based activation of immune components, i.e., neutrophils, macrophages, and other effector cells, may induce inflammation and alter the immune response. Here, it is essential to distinguish the acute and chronic modulations triggered by nanomaterials to determine the possible risks to human health. Nanomaterials size, shape, composition, surface charge, and deformability are factors controlling their uptake by immune cells and the resulting immune responses. The exterior corona of molecules adsorbed over nanomaterials surfaces also influences their immunological effects. Here, we review current nanoengineering trends for targeted immunomodulation with an emphasis on the design, safety, and potential toxicity of nanomaterials. First, we describe the characteristics of engineered nanomaterials that trigger immune responses. Then, the biocompatibility and immunotoxicity of nanoengineered particles are debated, because these factors influence applications. Finally, future nanomaterial developments in terms of surface modifications, synergistic approaches, and biomimetics are discussed.

Statistical optimization of process variables for agarase production using Microbacterium sp. SS5 strain from non-marine sources.

Agar oligosaccharides are thought to be valuable biomolecules with high bioactivity potential, along with a wide range of applications and advantages. The current study aimed to optimize the culture parameters required to produce agarase enzyme and agar oligosaccharides from industrial waste agar. Microbacterium spp. strain SS5 was isolated from a non-marine source and could synthesize oligo derivatives for use in a variety of industries ranging from food to pharmaceuticals. In addition, the strain and culture conditions were optimized to maximize extracellular agarase production. The bacterium grew best at pH 5.0 - 9.0, with an optimal pH of 7.5 - 8.0; temperatures ranging from 25 to 45 °C, with an optimal of 35 °C; and carbon and nitrogen concentrations of 0.5% each. Plackett-Burman experimental design and response surface methods were used to optimize various process parameters for agarase production by Microbacterium spp. strain SS5. Using the Plackett-Burman experimental design, eleven process factors were screened, and agar, beef extract, CaCl2, and beginning pH were found as the most significant independent variables affecting agarase production with confidence levels above 90%. To determine the optimal concentrations of the identified process factors on agarase production, the Box- Behnken design was used. Agarase production by Microbacterium spp. strain SS5 after optimization was 0.272 U/mL, which was determined to be greater than the result obtained from the basal medium (0.132 U/mL) before screening using Plackett-Burman and BBD with a fold increase of 2.06.

Hair and Nail-On-Chip for Bioinspired Microfluidic Device Fabrication and Biomarker Detection.

The advent of biosensors has tremendously increased our potential of identifying and solving important problems in various domains, ranging from food safety and environmental analysis, to healthcare and medicine. However, one of the most prominent drawbacks of these technologies, especially in the biomedical field, is to employ conventional samples, such as blood, urine, tissue extracts and other body fluids for analysis, which suffer from the drawbacks of invasiveness, discomfort, and high costs encountered in transportation and storage, thereby hindering these products to be applied for point-of-care testing that has garnered substantial attention in recent years. Therefore, through this review, we emphasize for the first time, the applications of switching over to noninvasive sampling techniques involving hair and nails that not only circumvent most of the aforementioned limitations, but also serve as interesting alternatives in understanding the human physiology involving minimal costs, equipment and human interference when combined with rapidly advancing technologies, such as microfluidics and organ-on-a-chip to achieve miniaturization on an unprecedented scale. The coalescence between these two fields has not only led to the fabrication of novel microdevices involving hair and nails, but also function as robust biosensors for the detection of biomarkers, chemicals, metabolites and nucleic acids through noninvasive sampling. Finally, we have also elucidated a plethora of futuristic innovations that could be incorporated in such devices, such as expanding their applications in nail and hair-based drug delivery, their potential in serving as next-generation wearable sensors and integrating these devices with machine-learning for enhanced automation and decentralization.

Protective effects of macromolecular polyphenols, metals (zinc, selenium, and copper) - Polyphenol complexes, and different organs with an emphasis on arsenic poisoning: A review.

For the potential health benefits and nutritional value, polyphenols are one of the secondary metabolites of plants that have received extensive research. It has anti-inflammatory and cytotoxicity-reducing properties in addition to a high antioxidant content. Macromolecular polyphenols and polysaccharides are biologically active natural polymers with antioxidant and anti-inflammatory potential. Arsenic is an ecologically toxic metalloid. Arsenic in drinking water is the most common way people come into contact with this metalloid. While arsenic is known to cause cancer, it is also used to treat acute promyelocytic leukemia (APL). The treatment's effectiveness is hampered by the adverse effects it can cause on the body. Oxidative stress, inflammation, and the inability to regulate cell death cause the most adverse effects. Polyphenols and other macromolecules like polysaccharides act as neuroprotectants by mitigating free radical damage, inhibiting nitric oxide (NO) production, lowering A42 fibril formation, boosting antioxidant levels, and controlling apoptosis and inflammation. To prevent the harmful effects of toxins, polyphenols and pectin lower oxidative stress, boost antioxidant levels, improve mitochondrial function, control apoptosis, and suppress inflammation. Therefore, it prevents damage to the heart, liver, kidneys, and reproductive system. This review aims to identify the effects of the polyphenols in conjugation with polysaccharides as an ameliorative strategy for arsenic-induced toxicity in various organs.

Environmental pollutants and their effects on human health.

Numerous environmental contaminants significantly contribute to human disease, affecting climate change and public and individual health, resulting in increased mortality and morbidity. Because of the scarcity of information regarding pollution exposure from less developed nations with inadequate waste management, higher levels of poverty, and limited adoption of new technology, the relationship between pollutants and health effects needs to be investigated more. A similar situation is present in many developed countries, where solutions are only discovered after the harm has already been done and the necessity for safeguards has subsided. The connection between environmental toxins and health needs to be better understood due to difficulties in quantifying exposure levels and a lack of systematic monitoring. Different pollutants are to blame for both chronic and acute disorders. Additionally, research becomes challenging when disease problems are seen after prolonged exposure. This review aims to discuss the present understanding of the association between environmental toxins and human health in bridging this knowledge gap. The genesis of cancer and the impact of various environmental pollutants on the human body's cardiovascular, respiratory, reproductive, prenatal, and neural health are discussed in this overview.

Onco-Pathogen Mediated Cancer Progression and Associated Signaling Pathways in Cancer Development.

Infection with viruses, bacteria, and parasites are thought to be the underlying cause of about 8-17% of the world's cancer burden, i.e., approximately one in every five malignancies globally is caused by an infectious pathogen. Oncogenesis is thought to be aided by eleven major pathogens. It is crucial to identify microorganisms that potentially act as human carcinogens and to understand how exposure to such pathogens occur as well as the following carcinogenic pathways they induce. Gaining knowledge in this field will give important suggestions for effective pathogen-driven cancer care, control, and, ultimately, prevention. This review will mainly focus on the major onco-pathogens and the types of cancer caused by them. It will also discuss the major pathways which, when altered, lead to the progression of these cancers.

A Systematic Role of Metabolomics, Metabolic Pathways, and Chemical Metabolism in Lung Cancer.

Lung cancer (LC) is considered as one of the leading causes of cancer-associated mortalities. Cancer cells' reprogrammed metabolism results in changes in metabolite concentrations, which can be utilized to identify a distinct metabolic pattern or fingerprint for cancer detection or diagnosis. By detecting different metabolic variations in the expression levels of LC patients, this will help and enhance early diagnosis methods as well as new treatment strategies. The majority of patients are identified at advanced stages after undergoing a number of surgical procedures or diagnostic testing, including the invasive procedures. This could be overcome by understanding the mechanism and function of differently regulated metabolites. Significant variations in the metabolites present in the different samples can be analyzed and used as early biomarkers. They could also be used to analyze the specific progression and type as well as stages of cancer type making it easier for the treatment process. The main aim of this review article is to focus on rewired metabolic pathways and the associated metabolite alterations that can be used as diagnostic and therapeutic targets in lung cancer diagnosis as well as treatment strategies.

Crosstalk between COVID-19 Infection and Kidney Diseases: A Review on the Metabolomic Approaches.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a respiratory disorder. Various organ injuries have been reported in response to this virus, including kidney injury and, in particular, kidney tubular injury. It has been discovered that infection with the virus does not only cause new kidney disease but also increases treatment difficulty and mortality rates in people with kidney diseases. In individuals hospitalized with COVID-19, urinary metabolites from several metabolic pathways are used to distinguish between patients with acute kidney injury (AKI) and those without. This review summarizes the pathogenesis, pathophysiology, treatment strategies, and role of metabolomics in relation to AKI in COVID-19 patients. Metabolomics is likely to play a greater role in predicting outcomes for patients with kidney disease and COVID-19 with varying levels of severity in the near future as data on metabolic profiles expand rapidly. Here, we also discuss the correlation between COVID-19 and kidney diseases and the available metabolomics approaches.

Fluro-Protein C-Phycocyanin Docked Silver Nanocomposite Accelerates Cell Migration through NFĸB Signaling Pathway.

Currently, there is a great demand for the development of nanomedicine aided wound tissue regeneration via silver doped nanoceuticals. Unfortunately, very little research is being carried out on antioxidants-doped silver nanometals and their interaction on the signaling axis during the bio-interface mechanism. In this study, c-phycocyanin primed silver nano hybrids (AgcPCNP) were prepared and analyzed for properties such as cytotoxicity, metal decay, nanoconjugate stability, size expansion, and antioxidant features. Fluctuations in the expression of marker genes during cell migration phenomena in in vitro wound healing scenarios were also validated. Studies revealed that physiologically relevant ionic solutions did not exhibit any adverse effects on the nanoconjugate stability. However, acidic, alkali, and ethanol solutions completely denatured the AgcPCNP conjugates. Signal transduction RT2PCR array demonstrated that genes associated with NFĸB- and PI3K-pathways were significantly (p < 0.5%) altered between AgcPCNP and AgNP groups. Specific inhibitors of NFĸB (Nfi) and PI3K (LY294002) pathways confirmed the involvement of NFĸB signaling axes. In vitro wound healing assay demonstrated that NFĸB pathway plays a prime role in the fibroblast cell migration. In conclusion, the present investigation revealed that surface functionalized AgcPCNP accelerated the fibroblast cell migration and can be further explored for wound healing biomedical applications.

Inhibitory effect of gallic acid from Thunbergia mysorensis against α-glucosidase, α-amylase, aldose reductase and their interaction: Inhibition kinetics and molecular simulations.

In this exploration, we assessed the antihyperglycaemic properties of methanol extract of flowers of Thunbergia mysorensis (MeT) against α-glucosidase, α-amylase and aldose reductase enzymes for the effective management of postprandial hyperglycemia. Hyperglycemia occurs when the body lacks enough insulin or is unable to correctly utilize it. MeT inhibited both the carbohydrate digestive enzymes (α-glucosidase and α-amylase) and aldose reductase, which are vital for the therapeutic control of postprandial hyperglycaemia. MeT was also found to have significant antioxidant activity. Using several spectroscopic approaches, the primary active component found in MeT was identified as gallic acid. With low Ki values, gallic acid significantly inhibited α-glucosidase (30.86 µg/mL) and α-amylase (6.50 µg/mL). Also, MeT and gallic acid both inhibited aldose reductase effectively, corresponding to an IC50 value of 3.31 and 3.05 µg/mL. Our findings imply that the presence of polyphenol compounds (identified via HPLC analysis) is more likely to be responsible for the antihyperglycaemic role exhibited by MeT via the inhibition of α-glucosidase and the polyol pathway. Further, gallic acid interacted with the key residues of the active sites of α-glucosidase (-6.4 kcal/mol), α-amylase (-5.8 kcal/mol) and aldose reductase (-5.8 kcal/mol) as observed in the protein-ligand docking. It was also predicted that gallic acid was stable inside the binding pockets of the target enzymes during molecular dynamics simulation. Overall, gallic acid derived from MeT via bioassay-guided isolation emerges as a natural antidiabetic drug and can be taken into in vivo and clinical studies shortly.Communicated by Ramaswamy H. Sarma.

Advances in the Lung Cancer Immunotherapy Approaches.

Despite the progress in the comprehension of LC progression, risk, immunologic control, and treatment choices, it is still the primary cause of cancer-related death. LC cells possess a very low and heterogeneous antigenicity, which allows them to passively evade the anticancer defense of the immune system by educating cytotoxic lymphocytes (CTLs), tumor-infiltrating lymphocytes (TILs), regulatory T cells (Treg), immune checkpoint inhibitors (ICIs), and myeloid-derived suppressor cells (MDSCs). Though ICIs are an important candidate in first-line therapy, consolidation therapy, adjuvant therapy, and other combination therapies involving traditional therapies, the need for new predictive immunotherapy biomarkers remains. Furthermore, ICI-induced resistance after an initial response makes it vital to seek and exploit new targets to benefit greatly from immunotherapy. As ICIs, tumor mutation burden (TMB), and microsatellite instability (MSI) are not ideal LC predictive markers, a multi-parameter analysis of the immune system considering tumor, stroma, and beyond can be the future-oriented predictive marker. The optimal patient selection with a proper adjuvant agent in immunotherapy approaches needs to be still revised. Here, we summarize advances in LC immunotherapy approaches with their clinical and preclinical trials considering cancer models and vaccines and the potential of employing immunology to predict immunotherapy effectiveness in cancer patients and address the viewpoints on future directions. We conclude that the field of lung cancer therapeutics can benefit from the use of combination strategies but with comprehension of their limitations and improvements.

Dual antibacterial and anti-inflammatory efficacy of a chitosan-chondroitin sulfate-based in-situ forming wound dressing.

None of the currently available wound dressings exhibit combined antibacterial and anti-inflammatory activity. Using polyelectrolyte complexation (PEC) between a cationic polysaccharide chitosan (CH) and an anionic glycosaminoglycan chondroitin sulfate (CS), we have developed a unique in-situ forming scaffold (CH-CS PEC), which develops at the wound site itself to influence the function of the wound bed cells. The current study demonstrated that CH-CS PEC could induce bacterial cell death through membrane pore formation and increased ROS production. Moreover, possibly due to its unique material properties including medium-soft viscoelasticity, porosity, and surface composition, CH-CS PEC could modulate macrophage function, increasing their phagocytic ability with low TNF-α and high IL-10 production. Faster wound closure and decreased CFU count was observed in an in-vivo infected wound model, with reduced NF-κB and increased VE-cadherin expression, indicating reduced inflammation and enhanced angiogenesis. In summary, this study exhibited that CH-CS PEC has substantial antibacterial and immunomodulatory properties.

Double functionalized haemocompatible silver nanoparticles control cell inflammatory homeostasis.

Infection, trauma, and autoimmunity trigger tissue inflammation, often leading to pain and loss of function. Therefore, approaches to control inflammation based on nanotechnology principles are being developed in addition to available methods. The metal-based nanoparticles are particularly attractive due to the ease of synthesis, control over physicochemical properties, and facile surface modification with different types of molecules. Here, we report curcumin conjugated silver (Cur-Ag) nanoparticles synthesis, followed by their surface functionalization with isoniazid, tyrosine, and quercetin, leading to Cur-AgINH, Cur-AgTyr, and Cur-AgQrc nanoparticles, respectively. These nanoparticles possess radical scavenging capacity, haemocompatibility, and minimal cytotoxicity to macrophages. Furthermore, the nanoparticles inhibited the secretion of pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α, and interleukin-1ß from macrophages stimulated by lipopolysaccharide (LPS). The findings reveal that the careful design of surface corona of nanoparticles could be critical to increasing their efficacy in biomedical applications.

Hesperidin and hesperetin against heavy metal toxicity: Insight on the molecular mechanism of mitigation.

Toxic heavy metals (THMs) are non-essential hazardous environmental pollutants with intractable health challenges in humans and animals. Exposure to lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), and chromium (Cr) are ubiquitous and unavoidable due to food contamination, mining, and industrial mobilization. They are triggers of tissue impairment and aberrant signaling pathways that cascade into several toxicities and pathologies. Each of Pb, Cd, Hg, As, Ni, and Cr aggravate oxidative inflammation, protein dysregulation, apoptotic induction, DNA damage, endocrine deficits, and mitochondrial dysfunction contributing to the pathophysiology of diseases. Hesperidin (HSD) and hesperetin (HST) are flavonoids from citrus fruits, and systematic investigations suggest their potential to combat the molecular alterations and toxicities induced by THMs. They mitigate heavy metal toxicity via antioxidant, anti-inflammatory, and anti-apoptotic effects via scavenging free radicals and modulation of ATPases, cell cycle proteins, and various cellular signaling pathways, including Nrf2/HO-1/ARE, PI3K/mTOR/Akt, MAPK/caspase-3/Bax/Bcl-2, iNOS/NF-κB/TNF-α/COX-2. This review summarized the mechanistic effects of heavy metal toxicity and the insights on molecular mechanisms underlying mitigation of heavy metal toxicity by HSD and HST. Hesperidin and hesperetin are potential flavonoids for the modulation of pathological signaling networks associated with THMs. Therefore, HSD and HST can be suggested as natural dietary agents and blockers of harmful effects of THMs.

Omicron variant infection and the associated immunological scenario.

The million-dollar question that has been the talk of the day is how effective the COVID 19 vaccines are against the Omicron variant. Still, there is no clear-cut answer to this question but several studies have concluded that this Variant of Concern (VOC) successfully weakens the neutralizing capability of the antibodies acquired from the COVID 19 vaccines and prior infections, which indicates that Omicron can easily bypass an individual's humoral immune response. However, the most significant confusion revolves around cell-mediated immunity tackling the Omicron variant. This paper aims to provide a clear idea about the status of the body's immune surveillance concerning the infection caused by the Omicron variant by producing the effectivity of the humoral and cell-mediated immunity in handling the same. This work also provides complete detail of the various characteristics of the Omicron variant and how it may be a blessing in disguise. The effectiveness of the current vaccines, the transmissibility rate of the variant compared to the other variants, and the importance of administering a booster dose to prevent the spread of this variant are also discussed. Finally, this work aims to bridge the gap between the past and the current status of the Omicron infection and sheds light on the hypothetical idea that herd immunity developed from the SARS-COV2 infection may help tackle other dangerous variants.

Apoptosis inducing metabolite from marine mangrove actinobacteria VITGAP173.

BACKGROUND: Marine actinobacteria have proven to be a remarkable source of bioactive metabolites. METHODS: The present study focused on the isolation of anticancer metabolites from marine actinobacteria. Streptomyces sp. VITGAP173 was found to have promising anticancer activity against breast cancer cell lines (MCF-7). RESULTS: Bioassay-guided fractionation was followed to identify the bioactive metabolites from crude ethyl acetate extract of VITGAP173, which yielded four fractions. Among the four fractions, fraction B exhibited the highest cytotoxic activity against MCF-7 cell lines. Further structural characterization of the fraction was done by FTIR and NMR spectroscopy. The fraction-2 induced cytotoxicity against MCF-7 cell lines and the half maximal inhibition (IC50) value was calculated as 4.7µg/ml. To elucidate the possible mechanism of cell death, MCF-7 cells were treated with fraction-2 for 24 hours and the morphological changes were examined using acridine orange - ethidium bromide (AO/EB) staining. The fraction also increased the reactive oxygen species (ROS) generation (Flow cytometry, DCFH-DA). The molecular mechanism of fraction-induced cell death was analysed by real-time PCR, which revealed that the fraction promotes apoptosis through the CHOP-ATF-4 pathway which is involved in ER stress signalling. CONCLUSION: The present findings suggest the apoptosis inducing potential of fraction-2 in breast cancer therapy.

Progressive Application of Marine Biomaterials in Targeted Cancer Nanotherapeutics.

The marine microenvironment harbors many unique species of organisms that produce a plethora of compounds that help mankind cure a wide range of diseases. The diversity of products from the ocean bed serves as potentially healing materials and inert vehicles carrying the drug of interest to the target site. Several composites still lay undiscovered under the blue canopy, which can provide treatment for untreated diseases that keep haunting the earth periodically. Cancer is one such disease that has been of interest to several eminent scientists worldwide due to the heterogenic complexity involved in the disease's pathophysiology. Due to extensive globalization and environmental changes, cancer has become a lifestyle disease continuously increasing exponentially in the current decade. This ailment requires a definite remedy that treats by causing minimal damage to the body's normal cells. The application of nanotechnology in medicine has opened up new avenues of research in targeted therapeutics due to their highly malleable characteristics. Marine waters contain an immense ionic environment that succors the production of distinct nanomaterials with exceptional character, yielding highly flexible molecules to modify, thus facilitating the engineering of targeted biomolecules. This review provides a short insight into an array of marine biomolecules that can be probed into cancer nanotherapeutics sparing healthy cells.

Potential role of green tea amino acid l-theanine in the activation of innate immune response by enhancing expression of cytochrome b558 responsible for the reactive oxygen species-generating ability of leukocytes.

l-Theanine (N-ethyl- l-glutamine) is an analog of l-glutamine and l-glutamic acid, accounts for up to 50% of all free amino acids in green tea, and elicits an umami taste. As l-theanine also shows various physiological activities including immune response-modifying activities, it is expected to be an excellent health-promoting phytochemical agent. To know the influences of l-theanine on the human innate immune response, we investigated the effect of l-theanine on the superoxide anion (O2 - )-generating system of leukocytes using U937 cells. The O2 - -generating system in leukocytes consists of membrane cytochrome b558 protein (a complex of p22-phox and gp91-phox proteins) and cytosolic p40-phox, p47-phox, and p67-phox proteins. Addition of 500 µM l-theanine caused remarkable enhancement of the all-trans retinoic acid (ATRA)-induced O2 - -generating activity (to ~470% of ATRA-treated cells), but not l-glutamine and l-glutamic acid. Semiquantitative RT-PCR showed that the transcription level of gp91-phox is significantly increased in ATRA and l-theanine-co-treated cells. Chromatin immunoprecipitation revealed that l-theanine enhances acetylations of Lys-9 and Lys-14 residues of histone H3 within the chromatin surrounding the promoter region of the gp91-phox gene. Immunoblotting demonstrated that membrane cytochrome b558 proteins remarkably accumulate in ATRA + l-theanine-treated cells. These results suggested that l-theanine brings about a remarkable accumulation of cytochrome b558 protein via upregulating the transcription of the gp91-phox gene during leukocyte differentiation, resulting in marked augmentation of the O2 - -generating ability, which is one of the most important functions of leukocytes responsible for the innate immune system.

A voyage from 3D to 4D printing in nanomedicine and healthcare: part II.

Recent advancements in biomedical tissue engineering are gaining wide interest. Implementing biology of living cells and organisms using technological solutions such as incorporating 4D printing and bioprinting for tissue regeneration/tissue repair, organ regeneration, early diagnosis of deadly diseases (particularly cancer, cardiac disorders and tuberculosis) has successfully opened a new generation of biomedical research. The present review primarily addresses the clinical application of 4D printing and bioprinting techniques for applications such as early detection of diseases and drug delivery. Notably, this review continues the discussion from part I regarding published informative data, in vitro and in vivo findings, commercial biosensors for early disease diagnosis, drug delivery and current challenges in 4D printing/bioprinting.