Quality of Life in Locally Advanced Carcinoma Rectum Patients During Various Phases of NACRT: An Indian Perspective.

In low- and middle-income countries (LMICs) including India, cancer patients have a poor prognosis because of late diagnosis and cases already grown to advanced stages, low cancer awareness and skewed cancer care facilities. In India, the incidence of colorectal cancer (CRC) is ranked the 4th most common (6.4%) in males and the 5th most common (3.4%) in females. The improvement in the cure rate of rectal cancer has increased life expectancy, and assessment of the quality of life (QoL) in these patients has become a fundamental requirement. Little is known about how the patients perceive these adverse effects during curatively intended radiotherapy. Although studies have investigated the various adverse effects that can occur with radiotherapy and chemotherapy in carcinoma rectum patients, these have not yet been critically appraised and synopsized to form a comprehensive review of their prevalence and effects on QoL. The study was designed to explore the QoL issues in locally advanced carcinoma rectum patients during various phases of neoadjuvant concurrent chemo-radiotherapy (NACCRT). The study was performed over a period of 2 years at a single super speciality cancer hospital in North India. Patients were selected as per the inclusion criteria and followed up with a standard questionnaire incorporating various aspects depicting QoL. The interview technique was used for collecting QoL data at four points, at baseline, midway during treatment, at the end of treatment and 4 weeks after completion of NACCRT, using EORTC QLQ C30, for QLQ CR29. Special care was taken to avoid observer bias in cases of language issues, and interpreters' services were utilised, and compared with the baseline pre-treatment scores, patients reported a statistically significant and large clinically meaningful change in the global health status, social functioning, fatigue (FACIT-F), appetite loss, anxiety, sore skin and male and female sexual function at the post-treatment time point. Statistically significant changes with moderate clinically meaningful changes were reported for the functional scales-physical, role and emotional functioning of the QLQ C30 questionnaire and body image and weight of the CR29 questionnaire. Similar moderate clinical changes were found in the symptom scales-fatigue, nausea and vomiting, insomnia, constipation and diarrhoea of QLQ C30 and stool frequency, embarrassment with bowel function, impotence and dyspareunia. These parameters returned to almost the pre-treatment values after 4 weeks of completion of NACRT. Since QoL is a relatively subjective variable, differences in human race, culture, education and social environment will have impacts on the results. International cooperation is needed to study the QoL in patients with multiple cultural backgrounds. The existing QoL questionnaire tools have been designed with Western countries in mind, and we did face multiple social issues. We suggest that many similar multicentre studies shall be required to essentially tap the accurate QoL-related issues keeping in mind the diverse social, economic, racial and educational backgrounds. As we deal with the ever-increasing cancer menace and better life expectancy, QoL issues shall be a major determinant of treatment success besides primary treatment. These factors should form an integral part of treatment modality, and adequate counselling must be performed prior to initiation of care.

Diagnostic accuracy of fine needle aspiration cytology of bone lesions: A study of Tertiary Care Institute.

AIMS AND OBJECTIVES: The aim is to study the spectrum and cytomorphological features of bone lesions and find out the diagnostic accuracy of Fine needle aspiration cytology (FNAC) on the same. MATERIALS AND METHODS: The study was a cross-sectional study conducted in the Department of Pathology and Orthopedics in a tertiary institute in north India over a period of 1 year in 55 patients. All the patients were subjected to FNAC of bone lesions followed by tru-cut or open bone biopsy. Cytosmears were stained with May Grunwald Giemsa and Hematoxylin and Eosin were done on biopsy specimens. Sensitivity and specificity were calculated in percentage with a 95% confidence interval with reference to biopsy specimens. RESULTS: Two peaks were observed; one between 11 and 40 years with 32 cases and another at 51 and 60 years with 12 cases. The male to female ratio was 1.4:1. In the present study, inflammatory lesions were present in 17 (31%) cases, 2 were tumor-like conditions; 10 (18%) cases of primary benign tumors, 26 (47.2%) cases were malignant. Out of these, 15 (27.2%) were primary malignant bone tumors and 11 (20%) were secondary in nature. The sensitivity, specificity, and diagnostic accuracy of the FNA of bone lesions were 55.17%, 79.04%, and 73.46%, respectively. CONCLUSION: Although there are a few limitations of FNAC such as low cellularity, small representative sample, and hemorrhagic aspirate, it can still be used as an initial diagnostic modality with proper clinical context for the management of bone lesions.

Integrating Nanotechnological Advancements of Disease-Modifying Anti-Rheumatic Drugs into Rheumatoid Arthritis Management.

Disease-modifying anti-rheumatic drugs (DMARDs) is a class of anti-rheumatic medicines that are frequently prescribed to patients suffering from rheumatoid arthritis (RA). Methotrexate, sulfasalazine, hydroxychloroquine, and azathioprine are examples of non-biologic DMARDs that are being used for alleviating pain and preventing disease progression. Biologic DMARDs (bDMARDs) like infliximab, rituximab, etanercept, adalimumab, tocilizumab, certolizumab pegol, and abatacept have greater effectiveness with fewer adverse effects in comparison to non-biologic DMARDs. This review article delineates the classification of DMARDs and their characteristic attributes. The poor aqueous solubility or permeability causes the limited oral bioavailability of synthetic DMARDs, while the high molecular weights along with the bulky structures of bDMARDs have posed few obstacles in their drug delivery and need to be addressed through the development of nanoformulations like cubosomes, nanospheres, nanoemulsions, solid lipid nanoparticles, nanomicelles, liposome, niosomes, and nanostructured lipid carrier. The main focus of this review article is to highlight the potential role of nanotechnology in the drug delivery of DMARDs for increasing solubility, dissolution, and bioavailability for the improved management of RA. This article also focusses on the different aspects of nanoparticles like their applications in biologics, biocompatibility, body clearance, scalability, drug loading, and stability issues.

A method for predicting linear and conformational B-cell epitopes in an antigen from its primary sequence.

B-cell is an essential component of the immune system that plays a vital role in providing the immune response against any pathogenic infection by producing antibodies. Existing methods either predict linear or conformational B-cell epitopes in an antigen. In this study, a single method was developed for predicting both types (linear/conformational) of B-cell epitopes. The dataset used in this study contains 3875 B-cell epitopes and 3996 non-B-cell epitopes, where B-cell epitopes consist of both linear and conformational B-cell epitopes. Our primary analysis indicates that certain residues (like Asp, Glu, Lys, and Asn) are more prominent in B-cell epitopes. We developed machine-learning based methods using different types of sequence composition and achieved the highest AUROC of 0.80 using dipeptide composition. In addition, models were developed on selected features, but no further improvement was observed. Our similarity-based method implemented using BLAST shows a high probability of correct prediction with poor sensitivity. Finally, we developed a hybrid model that combines alignment-free (dipeptide based random forest model) and alignment-based (BLAST-based similarity) models. Our hybrid model attained a maximum AUROC of 0.83 with an MCC of 0.49 on the independent dataset. Our hybrid model performs better than existing methods on an independent dataset used in this study. All models were trained and tested on 80 % of the data using a cross-validation technique, and the final model was evaluated on 20 % of the data, called an independent or validation dataset. A webserver and standalone package named "CLBTope" has been developed for predicting, designing, and scanning B-cell epitopes in an antigen sequence available at (https://webs.iiitd.edu.in/raghava/clbtope/).

A random forest model for predicting exosomal proteins using evolutionary information and motifs.

Non-invasive diagnostics and therapies are crucial to prevent patients from undergoing painful procedures. Exosomal proteins can serve as important biomarkers for such advancements. In this study, we attempted to build a model to predict exosomal proteins. All models are trained, tested, and evaluated on a non-redundant dataset comprising 2831 exosomal and 2831 non-exosomal proteins, where no two proteins have more than 40% similarity. Initially, the standard similarity-based method Basic Local Alignment Search Tool (BLAST) was used to predict exosomal proteins, which failed due to low-level similarity in the dataset. To overcome this challenge, machine learning (ML) based models were developed using compositional and evolutionary features of proteins achieving an area under the receiver operating characteristics (AUROC) of 0.73. Our analysis also indicated that exosomal proteins have a variety of sequence-based motifs which can be used to predict exosomal proteins. Hence, we developed a hybrid method combining motif-based and ML-based approaches for predicting exosomal proteins, achieving a maximum AUROC of 0.85 and MCC of 0.56 on an independent dataset. This hybrid model performs better than presently available methods when assessed on an independent dataset. A web server and a standalone software ExoProPred (https://webs.iiitd.edu.in/raghava/exopropred/) have been created to help scientists predict and discover exosomal proteins and find functional motifs present in them.

Cellular Responses to Widespread DNA Replication Stress.

Replicative DNA polymerases are blocked by nearly all types of DNA damage. The resulting DNA replication stress threatens genome stability. DNA replication stress is also caused by depletion of nucleotide pools, DNA polymerase inhibitors, and DNA sequences or structures that are difficult to replicate. Replication stress triggers complex cellular responses that include cell cycle arrest, replication fork collapse to one-ended DNA double-strand breaks, induction of DNA repair, and programmed cell death after excessive damage. Replication stress caused by specific structures (e.g., G-rich sequences that form G-quadruplexes) is localized but occurs during the S phase of every cell division. This review focuses on cellular responses to widespread stress such as that caused by random DNA damage, DNA polymerase inhibition/nucleotide pool depletion, and R-loops. Another form of global replication stress is seen in cancer cells and is termed oncogenic stress, reflecting dysregulated replication origin firing and/or replication fork progression. Replication stress responses are often dysregulated in cancer cells, and this too contributes to ongoing genome instability that can drive cancer progression. Nucleases play critical roles in replication stress responses, including MUS81, EEPD1, Metnase, CtIP, MRE11, EXO1, DNA2-BLM, SLX1-SLX4, XPF-ERCC1-SLX4, Artemis, XPG, FEN1, and TATDN2. Several of these nucleases cleave branched DNA structures at stressed replication forks to promote repair and restart of these forks. We recently defined roles for EEPD1 in restarting stressed replication forks after oxidative DNA damage, and for TATDN2 in mitigating replication stress caused by R-loop accumulation in BRCA1-defective cells. We also discuss how insights into biological responses to genome-wide replication stress can inform novel cancer treatment strategies that exploit synthetic lethal relationships among replication stress response factors.

A comparative study of the treatment outcome of moderately accelerated radiation fractionation (with concurrent chemotherapy in daily dosing) to conventional chemo-radiotherapy in locally advanced head and neck cancers: Supportive in a resource constrained environment.

BACKGROUND: In our country, head and neck cancers account for about a third of all cancers. Moreover, the patients typically present in advanced stages, which entails intensive multimodality therapy; but there is not much scope for improved survival outcomes. In view of this, a study was conducted to know the effects of treatment intensification, wherein moderately accelerated fractionation radiotherapy was given to patients presenting with advanced cancer of head and neck. This treatment was further intensified by accompanying radiation with concurrent cisplatin chemotherapy in daily doses. The control arm received the current standard therapy of conventional fractionation radiotherapy with weekly cisplatin chemotherapy. METHODS: The primary objective of the study was to determine the prospect of tumor control (TC), disease-free survival (DFS), and overall survival (OS). The secondary objective was to study acute toxicity and late toxicity of the highest grade in both treatment groups. The study was conducted on a total of 60 patients who presented with locally advanced squamous cell carcinoma of the head and neck. The 30 patients in the control group received conventional fractionated radiotherapy (five fractions per week) with weekly cisplatin chemotherapy (40 mg/m2), whereas the remaining 30 in the study group received moderately accelerated radiotherapy (six fractions per week with same treatment field) along with daily cisplatin chemotherapy (6 mg/m2) with a reduction in treatment time by 1 week. RESULTS: The overall response to therapy assessed as TC, DFS, and OS was compared, and no statistically significant difference between the two treatment arms was observed. However, the mean overall treatment time was reduced in the study group to 45 days as compared with 49 days in the control group (P = 0.001). The acute toxicities of xerostomia (P = 0.057) and skin (P = 0.052) and late toxicity of aspiration/laryngeal toxicity (P = 0.002) were higher in grade and number in the study group with accelerated fractionation. CONCLUSIONS: Hence, the study results suggest that it is a feasible option to combine the therapeutic benefits of accelerated fractionation radiotherapy with concurrent chemotherapy in patients with locally advanced head and neck carcinomas. There is a significant decrease in the overall treatment time and a considerable reduction in the load on the resource-constrained healthcare system. It would be equitable to point out that higher grade of few toxicities in the acceleration arm are likely due to doses to organs at risk being intensified with accelerated fractionation, which can now be delivered in a controlled manner with the latest high precision techniques, resulting in improved toxicity profile and quality of life which is the way forward for future studies.

Dissipation of tembotrione in maize and its effect on biochemical attributes of maize under mid-hill sub-humid zone.

The present study was undertaken to investigate the dissipation behavior of tembotrione in soil and its effect on the biochemical constituents of maize leaves and grain. The average recovery of tembotrione from soil, maize grain, and stover was in the range of 84.0 to 86.0%, 79.3 to 83.0%, and 81.0 to 84.4%, respectively, with RSD less than 10%. Half-life (DT50) of tembotrione ranged from 9 to 14 days at an application rate of 60 to 240 g ha-1. Terminal residues in soil, maize grain, and stover were below detectable levels (≤ 0.025 µg g-1) at studied application rates. The chemical attributes, i.e., total chlorophyll, total carotenoids, and carbohydrate content, of rice leaves were observed at monthly intervals (zero (2 h), 30, 60 days after the herbicide application) and at harvest for biochemical analysis and grain samples at maturity of the crop for carbohydrate content. The results revealed that total chlorophyll, total carotenoids, and carbohydrate content in maize leaves increased significantly with applied tembotrione treatments, and the maximum increase was noticed in treatment 120 g ha-1. A significant increase in total carbohydrate content in maize grain over the control was noticed in all the herbicide-applied treatments. It can be inferred that the application of tembotrione is safe in the production of food with better quality and food safety.

RAD54L regulates replication fork progression and nascent strand degradation in BRCA1/2-deficient cells.

RAD54L is a DNA motor protein with critical roles in homologous recombination DNA repair (HR). In vitro, RAD54L was also shown to catalyze the reversal and restoration of model replication forks. Little, however, is known about the role of RAD54L in regulating the dynamics of DNA replication in cells. Here, we show that RAD54L functions as a fork remodeler and restrains the progression of replication forks in human cells. Analogous to HLTF and FBH1, and consistent with a role in fork reversal, RAD54L catalyzes the slowing of fork progression in response to replication stress. In BRCA1/2-deficient cells, RAD54L activity leads to nascent strand DNA degradation, and loss of RAD54L reduces DNA double-strand break formation. Using a separation-of-function mutation, we show that RAD54L-mediated fork restraint depends on its ability to catalyze branch migration. Our results reveal a new role for RAD54L in regulating the dynamics of replication forks in cells and highlight the impact of RAD54L function on the treatment of patients with BRCA1/2-deficient tumors.

Understanding the mechanistic pathways and clinical aspects associated with protein and gene based biomarkers in breast cancer.

Cancer is one of the most widespread and severe diseases with a huge mortality rate. In recent years, the second-leading mortality rate of any cancer globally has been breast cancer, which is one of the most common and deadly cancers found in women. Detecting breast cancer in its initial stages simplifies treatment, decreases death risk, and recovers survival rates for patients. The death rate for breast cancer has risen to 0.024 % in some regions. Sensitive and accurate technologies are required for the preclinical detection of BC at an initial stage. Biomarkers play a very crucial role in the early identification as well as diagnosis of women with breast cancer. Currently, a wide variety of cancer biomarkers have been discovered for the diagnosis of cancer. For the identification of these biomarkers from serum or other body fluids at physiological amounts, many detection methods have been developed. In the case of breast cancer, biomarkers are especially helpful in discovering those who are more likely to develop the disease, determining prognosis at the time of initial diagnosis and choosing the best systemic therapy. In this study we have compiled various clinical aspects and signaling pathways associated with protein-based biomarkers and gene-based biomarkers.

To compare neoadjuvant concurrent chemo-radiotherapy followed by surgery and neoadjuvant chemotherapy followed by surgery in carcinoma esophagus patients: A single institutional study in the Indian population.

Objective: This single institutional study compared neoadjuvant concurrent chemo-radiotherapy (NACCRT) and neoadjuvant chemotherapy (NACT) followed by surgery in locally advanced middle and lower-1/3 carcinoma esophagus patients in terms of toxicity, clinical response, operative complications, disease downstaging, resection rates, pathological response, recurrence, and survival. Methods: This randomized prospective comparative study comprised 40 consecutive patients divided equally between two study arms NACCRT (n = 20; 41.4 Gy radiation dose; carboplatin area under the curve (AUC) 2/paclitaxel 50 mg/m2; 5 cycles) and NACT (n = 20; carboplatin AUC 5/paclitaxel 175 mg/m2; 2 cycles) from March 2014 to December 2016. Follow-up was done for 4 years. Chi-square test, Fischer's-exact test were used for comparative analysis and Kaplan-Meier analysis for survival. Results: Statistically significant esophagitis in NACCRT and peripheral-neuropathy in NACT was observed (P < 0.001). NACCRT recorded more postoperative complications, higher complete resection (R0) rates, and pathologically complete response (pCR). Tumor downstaging was significant in both study groups (n < 0.001). Four-year median disease-free survival (DFS) and overall survival (OS) were 28.50 months and 38 months in NACCRT versus 28 months and 35.5 months in NACT, respectively. In both NACCRT and NACT, pCR cases showed improved median DFS and OS compared to pathological partial response (pPR) (n < 0.001). Conclusion: This study demonstrated significant activity and tolerable toxicity of taxane-based therapy in NACCRT and NACT. Both groups recorded no survival benefit over each other, although pCR cases resulted in statistically significant survival advantage compared to clinical partial response. NACCRT resulted in lesser toxicity, numerically higher R0-resection, pCRs, median DFS, and OS compared to NACT.

Current trends in epigenetic, cellular and molecular pathways in management of rheumatoid arthritis.

Rheumatoid arthritis is a systemic chronic polyarticular autoimmune disorder of joints and joint membrane mainly affecting feet and hands. The pathological manifestation of the disease includes infiltration of immune cells, hyperplasia of the lining of synovium, formation of pannus and bone and cartilage destruction. If left untreated, the appearance of small focal necrosis, adhesion of granulation, and formation of fibrous tissue on the surface of articular cartilage is noted. The disease primarily affects nearly 1% of the population globally, women being more affected than men with a ratio 2:1 and can initiate regardless of any age. The synovial fibroblast in rheumatoid arthritis individuals exhibits an aggressive phenotype which upregulates the manifestation of protooncogenes, adhesive compounds, inflammatory cytokines and matrix-deteriorating enzymes. Apart from the inflammatory effects of cytokines, chemokines are also noted to induce swelling and pain in arthritic individuals by residing in synovial membrane and forming pannus. The current treatment of rheumatoid arthritis includes treatment with non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, treatment with biologics such as inhibitors of TNF-α, interleukins, platelet activating factor, etc. which provides significant relief from symptoms and aids in management of the disease. The current review highlights the pathogenesis involved in the onset of rheumatoid arthritis and also covers epigenetic, cellular and molecular parameters associated with it to aid better and advanced therapeutic approaches for management of the debilitating disease.

Comparison of the molecular profiling of core biopsy with surgical specimens in breast cancers and the effect of neoadjuvant therapy on the same - A North Indian study.

Aims and Objectives: The purpose of this study was to determine the concordance of core needle biopsy (CNB) and surgical specimens for determining the molecular profiling and to observe the changes in the same after neoadjuvant chemotherapy. Materials and Methods: This was a cross-sectional study over a period of one year on 95 cases. Immunohistochemical (IHC) staining was done as per the staining protocol in a fully automated BioGenex Xmatrx staining machine. Results: On CNB, estrogen receptor (ER) positivity was seen in 58 out of 95 cases, comprising 61% of the total, and on mastectomy, it was positive in 43 (45%) cases. Progesterone receptor (PR) positivity was seen in 59 (62%) cases on CNB and 44 (46%) cases on mastectomy. Total 7 (7%) were human epidermal growth factor receptor 2 (HER2)/neu positive on CNB and 8 (8%) on mastectomy, respectively. There were 15 (15.7%) that showed discordant results after neoadjuvant therapy. Estrogen status changed from negative to positive in 1 (7%) case and positive to negative in 14 (93%) cases. Progesterone status changed from positive to negative in all 15 cases (100%). There was no change in the HER2/neu status. The agreement of hormone receptor status between CNB and subsequent mastectomy in the present study was found to be substantial (kappa value for ER, PR, and HER2neu as 0.608, 0.648, and 0.648, respectively. Conclusion: IHC is a cost-effective method to assess hormone receptor expression. This study shows that ER, PR, and HER2/neu expression in CNB should be reassessed in excision specimens for the better management of endocrine therapy.

A Web-Based Method for the Identification of IL6-Based Immunotoxicity in Vaccine Candidates.

Interleukin 6 (IL6) is a major pro-inflammatory cytokine that plays a pivotal role in both innate and adaptive immune responses. In the past, a number of studies reported that high level of IL6 promotes the proliferation of cancer, autoimmune disorders, and cytokine storm in COVID-19 patients. Thus, it is extremely important to identify and remove the antigenic regions from a therapeutic protein or vaccine candidate that may induce IL6-associated immunotoxicity. In order to overcome this challenge, our group has developed a computational tool, IL6pred, for discovering IL6-inducing peptides in a vaccine candidate. The aim of this chapter is to describe the potential applications and methodology of IL6pred. It sheds light on the prediction, designing, and scanning modules of IL6pred webserver and standalone package ( https://webs.iiitd.edu.in/raghava/il6pred/ ).

Targeting multifunctional magnetic nanowires for drug delivery in cancer cell death: an emerging paradigm.

Apoptosis, often known as programmed cell death is a mechanism used by numerous species to maintain tissue homeostasis. The process leading to cell death is complicated because it requires the stimulation of caspases. According to several studies, nanowires have important medical benefits, can kill cells by adhering to cancer cells, destroying them, and killing the entire cell using a triple attack that integrates vibration, heat, and drug delivery to trigger apoptosis. The sewage effluents and industrial, fertilizer and organic wastes decomposition can produce elevated levels of chemicals in the environment which may interrupt the cell cycle and activate apoptosis. The purpose of this review is to give a thorough summary of the evidence that is currently available on apoptosis. Current review discussed topics like the morphological and biochemical alterations that occur during apoptosis, as well as the various mechanisms that cause cell death, including the intrinsic (or mitochondrial), extrinsic (or death receptor), and intrinsic endoplasmic reticulum pathway. The apoptosis reduction in cancer development is mediated by (i) an imbalance between pro- and anti-apoptotic proteins, such as members of the B-cell lymphoma-2 (BCL2) family of proteins, tumour protein 53 and inhibitor of apoptosis proteins, (ii) a reduction in caspase activity, and (iii) impaired death receptor signalling. This review does an excellent task of outlining the function of nanowires in both apoptosis induction and targeted drug delivery for cancer cells. A comprehensive summary of the relevance of nanowires synthesised for the purpose of inducing apoptosis in cancer cells has been compiled collectively.

A web server for predicting and scanning of IL-5 inducing peptides using alignment-free and alignment-based method.

Interleukin-5 (IL-5) can act as an enticing therapeutic target due to its pivotal role in several eosinophil-mediated diseases. The aim of this study is to develop a model for predicting IL-5 inducing antigenic regions in a protein with high precision. All models in this study have been trained, tested and validated on experimentally validated 1907 IL-5 inducing and 7759 non-IL-5 inducing peptides obtained from IEDB. Our primary analysis indicates that IL-5 inducing peptides are dominated by certain residues like Ile, Asn, and Tyr. It was also observed that binders of a wide range of HLA alleles can induce IL-5. Initially, alignment-based methods have been developed using similarity and motif search. These alignment-based methods provide high precision but poor coverage. In order to overcome this limitation, we explore alignment-free methods which are mainly machine learning-based models. Firstly, models have been developed using binary profiles and eXtreme Gradient Boosting-based model achieved a maximum AUC of 0.59. Secondly, composition-based models have been developed and our dipeptide-based random forest model achieved a maximum AUC of 0.74. Thirdly, random forest model developed using selected 250 dipeptides and achieved AUC 0.75 and MCC 0.29 on validation dataset; best among alignment-free models. In order to improve the performance, we developed an ensemble or hybrid method that combined alignment-based and alignment-free methods. Our hybrid method achieved AUC 0.94 with MCC 0.60 on a validation/independent dataset. The best hybrid model developed in this study has been incorporated into the user-friendly web server and a standalone package named 'IL5pred' (https://webs.iiitd.edu.in/raghava/il5pred/).

Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics.

The liver is a vital organ that plays a crucial role in the physiological operation of the human body. The liver controls the body's detoxification processes as well as the storage and breakdown of red blood cells, plasma protein and hormone production, and red blood cell destruction; therefore, it is vulnerable to their harmful effects, making it more prone to illness. The most frequent complications of chronic liver conditions include cirrhosis, fatty liver, liver fibrosis, hepatitis, and illnesses brought on by alcohol and drugs. Hepatic fibrosis involves the activation of hepatic stellate cells to cause persistent liver damage through the accumulation of cytosolic matrix proteins. The purpose of this review is to educate a concise discussion of the epidemiology of chronic liver disease, the pathogenesis and pathophysiology of liver fibrosis, the symptoms of liver fibrosis progression and regression, the clinical evaluation of liver fibrosis and the research into nanotechnology-based synthetic and herbal treatments for the liver fibrosis is summarized in this article. The herbal remedies summarized in this review article include epigallocathechin-3-gallate, silymarin, oxymatrine, curcumin, tetrandrine, glycyrrhetinic acid, salvianolic acid, plumbagin, Scutellaria baicalnsis Georgi, astragalosides, hawthorn extract, and andrographolides.

ViralVacDB: A manually curated repository of viral vaccines.

Over the years, numerous vaccines have been developed against viral infections; however, a complete database that provides comprehensive information on viral vaccines has been lacking. In this review, along with our freely accessible database ViralVacDB, we provide details of the viral vaccines, their type, routes of administration and approving agencies. This repository systematically covers additional information such as disease name, adjuvant, manufacturer, clinical status, age and dosage against 422 viral vaccines, including 145 approved vaccines and 277 in clinical trials. We anticipate that this database will be highly beneficial to researchers and others working in pharmaceuticals and immuno-informatics.