Glycoconjugates: Advances in modern medicines and human health.

Glycans and their glycoconjugates are complex biomolecules that are crucial for various biological processes. Glycoconjugates are found in all domains of life. They are covalently linked to key biomolecules such as proteins and lipids to play a pivotal role in cell signaling, adhesion, and recognition. The diversity of glycan structures and the associated complexity of glycoconjugates is the reason for their role in intricate biosynthetic pathways. Glycoconjugates play an important role in various diseases where they are actively involved in the immune response as well as in the pathogenicity of infectious diseases. In addition, various autoimmune diseases have been linked to glycosylation defects of different biomolecules, making them an important molecule in the field of medicine. The glycoconjugates have been explored for the development of therapeutics and vaccines, representing a breakthrough in medical science. They also hold significance in research studies to understand the mechanisms behind various biological processes. Finally, glycoconjugates have found an emerging role in various industrial and environmental applications which have been discussed here.

Screening of potential antiplasmodial agents targeting cysteine protease-Falcipain 2: a computational pipeline.

The spread of antimalarial drug resistance is a substantial challenge in achieving global malaria elimination. Consequently, the identification of novel therapeutic candidates is a global health priority. Malaria parasite necessitates hemoglobin degradation for its survival, which is mediated by Falcipain 2 (FP2), a promising antimalarial target. In particular, FP2 is a key enzyme in the erythrocytic stage of the parasite's life cycle. Here, we report the screening of approved drugs listed in DrugBank using a computational pipeline that includes drug-likeness, toxicity assessments, oral toxicity evaluation, oral bioavailability, docking analysis, maximum common substructure (MCS) and molecular dynamics (MD) Simulations analysis to identify capable FP2 inhibitors, which are hence potential antiplasmodial agents. A total of 45 drugs were identified, which have positive drug-likeness, no toxic features and good bioavailability. Among these, six drugs showed good binding affinity towards FP2 compared to E64, an epoxide known to inhibit FP2. Notably, two of them, Cefalotin and Cefoxitin, shared the highest MCS with E64, which suggests that they possess similar biological activity as E64. In an investigation using MD for 100 ns, Cefalotin and Cefoxitin showed adequate protein compactness as well as satisfactory complex stability. Overall, these computational approach findings can be applied for designing and developing specific inhibitors or new antimalarial agents for the treatment of malaria infections.Communicated by Ramaswamy H. Sarma.

Monitoring the distribution pattern and invasion status of Ageratina adenophora across elevational gradients in Sikkim Himalaya, India.

Understanding the spread intensity and population dynamics of invasive plant species is a prerequisite for developing management strategies in the Himalayan Forest ecosystems that are experiencing an accelerated rate of climate change. Although there are studies on the occurrence of few invasive species in the Himalayan ecosystems, systematic information on their intensity of spread and species association is still missing. Considering existing data gaps, we aimed to assess the intensity of spread and distribution pattern of A. adenophora, one of the high-concern invasive species (HiCIS) of India that is causing havoc in the Himalayas, across an elevational gradient. Field data were collected in 2018 and 2021 in the Indian federal state of Sikkim, located in the Eastern Himalayas. We analyzed the population status and species association of A. adenophora along an elevational gradient ranging from > 600 m to 2700 m above sea level, which was divided into seven gradients of 300 m width, and each gradient was further randomly sampled. Overall, 81 species were present in association with A. adenophora, including 58 herbs, 19 shrubs, and 4 climbers, belonging to 30 families and 67 genera in the region. No other species continuously co-occurred along with A. adenophora throughout the elevation ranging from > 600 m to 2700 m. The species observed increased frequency (100%), density (40.51 ind./100 m2), and basal cover (11.25 cm2/m2) in the elevational gradient 1500-1800 m in 2018. In 2021, A. adenophora dominated the highest elevational gradient (< 2400-2700 m) with increased frequency (99.96%), density (58.41 ind./100m2), and basal cover (42.54 cm2/100m2), which demonstrated rapid invasion and improved plant health and reproductive vigor in comparison to the lower elevational gradient in Sikkim Himalaya. Despite being completely absent at the highest elevation (< 2400-2700 m), in 2018, it observed gregarious spread at the highest elevation in 2021, which is of serious concern to ecologists. The presence of the targeted species in all seven studied altitudinal gradients reflects stage III of the species invasion. An enormous shift in the distribution pattern along elevational gradients within a short time span is alarming for the Himalayan ecosystem since it is becoming a thriving habitat for invasive species owing to anthropogenic activity. We mapped the potential geographical extent using the species distribution model (SDM) and predicted the suitable habitat of distribution in Sikkim Himalaya. In order to curtail the spread and counteract the negative impact of this species on native vegetation in Sikkim Himalaya and ultimately reverse the process, local and regional initiatives for its biological control and management must be taken.

An unusual case of adamantinoma of long bone.

Adamantinoma of the long bones is an exceedingly rare and slow-growing tumor that affects the diaphysis of long bones, particularly the tibia. Based on the pattern of the epithelial cell component and the presence or absence of the osteofibrous dysplasia-like element, several histological variants have been described, such as (i) tubular (the most frequent), (ii) basaloid, (iii) squamous, (iv) spindle variant, (v) osteofibrous dysplasia -like variant, and (vi) Ewing's sarcoma - like adamantinoma (the least frequent). The diagnosis may be challenging since this tumor may be mistakenly interpreted as carcinoma, myoepithelial tumor, osteofibrous dysplasia, and vascular tumor. We report the case of a 41-year-old male who presented with swelling over the right leg associated with pain. The X-ray showed a lytic lesion of the right-sided tibia. The diagnosis of adamantinoma was made based on the clinico-radiological, histomorphology, and immunohistochemical findings. Histologically, classic adamantinoma is a biphasic tumor characterized by epithelial and osteofibrous components in varying proportions and differentiating patterns. The diagnosis can be confirmed by immunohistochemistry for demonstrating sparse epithelial cell nests when the radiological features are strongly consistent with adamantinoma. This case is highlighted because the epithelial component can lead to a misdiagnosis, particularly when the clinico-radiological features are overlooked. Adamantinoma of long bones has the potential for local recurrence and may metastasize to the lungs, lymph nodes, or other bones. The prognosis is good if early intervention is taken.

An unusual case of adamantinoma of long bone

Adamantinoma of the long bones is an exceedingly rare and slow-growing tumor that affects the diaphysis of long bones, particularly the tibia. Based on the pattern of the epithelial cell component and the presence or absence of the osteofibrous dysplasia-like element, several histological variants have been described, such as (i) tubular (the most frequent), (ii) basaloid, (iii) squamous, (iv) spindle variant, (v) osteofibrous dysplasia -like variant, and (vi) Ewing's sarcoma - like adamantinoma (the least frequent). The diagnosis may be challenging since this tumor may be mistakenly interpreted as carcinoma, myoepithelial tumor, osteofibrous dysplasia, and vascular tumor. We report the case of a 41-year-old male who presented with swelling over the right leg associated with pain. The X-ray showed a lytic lesion of the right-sided tibia. The diagnosis of adamantinoma was made based on the clinico-radiological, histomorphology, and immunohistochemical findings. Histologically, classic adamantinoma is a biphasic tumor characterized by epithelial and osteofibrous components in varying proportions and differentiating patterns. The diagnosis can be confirmed by immunohistochemistry for demonstrating sparse epithelial cell nests when the radiological features are strongly consistent with adamantinoma. This case is highlighted because the epithelial component can lead to a misdiagnosis, particularly when the clinico-radiological features are overlooked. Adamantinoma of long bones has the potential for local recurrence and may metastasize to the lungs, lymph nodes, or other bones. The prognosis is good if early intervention is taken.

Phagocytosis of Gut Bacteria by Entamoeba histolytica.

The protist parasite Entamoeba histolytica causes amoebiasis, a major public health problem in developing countries. Only a small fraction of patients infected with the parasite display invasive disease involving colon or extra intestinal tissues such as liver. E. histolytica exists as two distinct forms, cysts, the infective form, and trophozoites, that are responsible for disease pathology. The latter multiply in the large intestine occasionally causing disease. The large intestine in humans is populated by a number of different bacterial communities and amoebic cells grow in their midst using some as food material. Several studies have shown relationship between bacteria and E. histolytica growth and virulence. However, an understanding of this relationship in human gut environment is not clear. We have investigated the possibility that there may be specific interaction of amoeba with different bacteria present in the gut environment by using a metagenomic pipe line. This was done by incubating bacteria isolated from human fecal material with E. histolytica and then identifying the bacterial population isolated from amoebic cells using a rRNA based metagenomic approach. Our results show that the parasite prefers a few bacterial species. One of these species is Lactobacillus ruminus which has never shown to be associated with E. histolytica.

Microfilariae of Wuchereriabancrofti in Testicular Aspirate.

Present study deals with results of fine needle aspiration of both the testes in a patient with azoospermia. Surprisingly, aspiration of right testis revealed large number of microfilariae in the smears. Conversely, left testicular aspirate showed few spermatogonia. However, microfilariae were not detected in venous blood smears. Findings of this study suggested possible role of Wuchereriabancrofti in causation of azoospermia.

Effects of the Exclusive Enteral Nutrition on the Microbiota Profile of Patients with Crohn's Disease: A Systematic Review.

The mechanisms behind the efficacy of exclusive enteral nutrition (EEN) in Crohn's disease (CD) remain poorly understood, despite the high rate of treatment response. Evidence accumulated in the last 20 years suggests that a positive shift of the disrupted microbiota is one of the treatment effects. The purpose of this study was to critically review and summarize data reporting the microbiological effects of EEN in patients with CD. Fourteen studies were considered in the review, overall involving 216 CD patients on EEN. The studies were heterogeneous in methods of microbiota analysis and exclusion criteria. The most frequently reported effect of EEN was a reduction in microbiota diversity, reversible when patients returned to a normal diet. The effect of EEN on specific bacteria was very variable in the different studies, partially due to methodological limitations of the mentioned studies. The EEN seem to induce some metabolomic changes, which are different in long-term responder patients compared to patients that relapse earlier. Bacterial changes can be relevant to explaining the efficacy of EEN; however, microbiological data obtained from rigorously performed studies and derived from last generation techniques are largely inconsistent.

Recovery and purification of oligosaccharides from copra meal by recombinant endo-ß-mannanase and deciphering molecular mechanism involved and its role as potent therapeutic agent.

Production of manno-oligosaccharides (MOSs) from pretreated and defatted copra meal (dFCO) hydrolysis was achieved by endo-mannanase. Structural characterization of dFCO by FT-IR and NMR exhibited resemblance with galactomannan. The time-dependent hydrolysis of dFCO by recombinant endo-ß-(1 → 4)-mannanase of Clostridium thermocellum by TLC and HPAEC displayed the release of mannose and MOSs mannobiose and mannotriose. Purified MOSs yielded 40 % mannobiose and 18 % mannotriose confirmed by mass spectroscopy which showed mannobiose (m/z = 365) and mannotriose (m/z = 527). The homology based structural analysis of catalytic endo-mannanase (CtManT) showed the catalytic core composed of Glu181 and Glu300 acting as acid/base and Glu288 as a nucleophile during galactomannan hydrolysis. Sub-site mapping of CtManT exhibited two aglycone and four glycone sites at cleavage sites existing on either side of ß-(1 → 4)-linkage of galactomannan. Isolated MOSs displayed potential prebiotic characteristics and supported higher growth of probiotic Lactobacillus acidophilus and Bifidobacterium infantis than with standard inulin. Moreover, MOSs displayed over 97 % tolerance to simulated gastric juice, intestinal fluid, and α-amylase proving its potential as a stable prebiotic over inulin. In vitro cytotoxicity assay of MOSs (500 µg/mL) on human epithelial colorectal adenocarcinoma cell line (HT-29) demonstrated 60 % decreased viability of cells after 48 h displaying anti-tumorigenic property.

Titers of anti-tissue transglutaminase antibody correlate well with severity of villous abnormalities in celiac disease.

GOALS: We reviewed our celiac disease (CeD) database to study if anti-tissue transglutaminase (tTG) antibody (ab) titers correlate with severity of villous abnormalities in Indian patients and to find out a cutoff value of anti-tTG ab fold-rise, which could best predict CeD. BACKGROUND: Guidelines for diagnosing CeD suggest that biopsy could be avoided in some patients with high anti-tTG ab titer. STUDY: We reviewed a cohort of 366 anti-tTG ab-positive individuals in whom duodenal biopsies were performed. Anti-tTG ab was obtained before initiation of gluten-free diet. Anti-tTG ab results were expressed in terms of fold-rise by calculating ratio of observed values with cutoff value. CeD was diagnosed if in addition to positive serology, patients had villous atrophy (>Marsh grade 2) and unequivocal response to gluten-free diet. RESULTS: The mean anti-tTG fold-rise in groups with Marsh grade ≤2 was 2.6 (±2.5), grade 3a was 4.0 (±3.9), 3b was 5.7 (±5.1), and 3c was 11.8 (±8.0). The positive likelihood ratio for diagnosing CeD was 15.4 and 27.4 at 12- and 14-fold-rise of anti-tTG ab titer, respectively. The positive predictive value of diagnosis of CeD was 100% when anti-tTG ab titer was 14-fold higher over the cutoff value. Fifty-seven (43.9%) individuals with anti-tTG titer rise <2-fold high also had CeD. CONCLUSIONS: As severity of villous abnormality increases, titer of anti-tTG also rises. Presence of villous atrophy can be predicted at very high anti-tTG ab titer. In contrast to emerging belief, mucosal biopsies should be performed even if anti-tTG ab titer is <2 times, because many patients with CeD have low titers.

High prevalence of human metapneumovirus subtype B in cases presenting as severe acute respiratory illness: an experience at tertiary care hospital.

PURPOSE: A comparatively newly discovered human metapneumovirus (HMPV) has emerged as an important cause of severe acute respiratory illness (SARI), second only to respiratory syncytial virus (RSV). RSV and HMPV taxonomically belong to same family and subfamily, and their clinical presentation and seasonal distribution are also seemed to be indistinguishable. Present study was planned to know the epidemiology and prevalence of HMPV and RSV in patients presented as SARI in a tertiary care hospital. METHODS: Nasopharyngeal aspirate of 440 patients fulfilling World Health Organization criteria of SARI, enrolled during a 2-year study period, were collected and tested for the presence of RSV, HMPV and their subtypes A and B by real time polymerase chain reaction along with other respiratory viruses, viz influenza A, B, parainfluenza 1, 2, 3, 4, adenovirus, measles virus and bocavirus. The demographic details, clinical profile, underlying diseases, clinical diagnosis at the time of admission and seasonal distribution were studied and analyzed statistically. RESULTS: Overall positivity of RSV was 14.3% (24.68% in <5 years) and of HMPV was 3.63% (5.1% in <5 years and 5.08% in 6-12 years). Among RSV, subtype A (89%), and among HMPV, genotype B (68.8%) were predominating. Adults having underlying chronic obstructive pulmonary disease were more prone to acquire RSV and HMPV infections. RSV and HMPV positivity was restricted to winter season. We are reporting replacement of RSV with HMPV in this population. CONCLUSIONS: HMPV has emerged as an important cause of SARI in children <12 years of age. Alternative predominance of RSV and HMPV is an important observation.

Real-time analysis of gut flora in Entamoeba histolytica infected patients of Northern India.

BACKGROUND: Amebic dysentery is caused by the protozoan parasite Entamoeba histolytica and the ingestion of quadrinucleate cyst of E. histolytica from fecally contaminated food or water initiates infection. Excystation occurs in the lumen of small intestine, where motile and potentially invasive trophozoites germinate from cysts. The ability of trophozoites to interact and digest gut bacteria is apparently important for multiplication of the parasite and its pathogenicity; however the contribution of resident bacterial flora is not well understood. We quantified the population of Bacteroides, Bifidobacterium, Ruminococcus, Lactobacillus, Clostridium leptum subgroup, Clostridium coccoides subgroup, Eubacterium, Campylobacter, Methanobrevibacter smithii and Sulphur reducing bacteria using genus specific primers in healthy (N = 22) vs amebic patients (E. histolytica positive, N = 17) stool samples by Real-time PCR. RESULTS: Absolute quantification of Bacteroides (p = .001), Closrtridium coccoides subgroup (p = 0.002), Clostridium leptum subgroup (p = 0.0001), Lactobacillus (p = 0.037), Campylobacter (p = 0.0014) and Eubacterium (p = 0.038) show significant drop in their population however, significant increase in Bifdobacterium (p = 0.009) was observed where as the population of Ruminococcus (p = 0.33) remained unaltered in healthy vs amebic patients (E. histolytica positive). We also report high prevalence of nimE gene in stool samples of both healthy volunteers and amebic patients. No significant decrease in nimE gene copy number was observed before and after the treatment with antiamebic drug. CONCLUSIONS: Our results show significant alteration in predominant gut bacteria in E. histolytica infected individuals. The frequent episodes of intestinal amoebic dysentery thus result in depletion of few predominant genera in gut that may lead to poor digestion and absorption of food in intestine. It further disturbs the homeostasis between gut epithelium and bacterial flora. The decrease in beneficial bacterial population gives way to dysbiosis of gut bacteria which may contribute to final outcome of the disease. Increase in the copy number of nimE gene harboring bacteria in our population reflects possible decrease in the availability of metronidazole drug during treatment of amoebiasis.