Humoral and cellular immunity to SARS-CoV-2 following vaccination with non-mRNA vaccines in adolescent/young adults with cancer: A prospective cohort study.

BACKGROUND: Data on SARS-CoV-2 vaccine responsiveness in adolescent/young adult (AYA) cancer patients are sparse. The present study assessed humoral and cellular immune responses post-vaccination in this population. METHODS: In this prospective study, patients aged 12-30 years undergoing cancer therapy ("on therapy") and survivors ("off therapy") were recruited. Anti-receptor binding domain (RBD) protein IgG levels were measured at baseline, four weeks post-first vaccine dose (T1), and six weeks post-second dose (T2). Cellular immunity was assessed using activation-induced markers and intracellular cytokine staining in a patient subset. The primary outcome was to quantify humoral responses in both cohorts at T2 compared to baseline. Clinical predictors of log antibody titres at T2 were identified. RESULTS: Between April-December 2022, 118 patients were recruited of median age 15.4 years. Among them, 77 (65.2 %) were in the "on therapy" group, and 77 (65.2 %) had received the BBV152 vaccine. At baseline, 108 (91.5 %) patients were seropositive for anti-RBD antibody. The log anti-RBD titre rose from baseline to T2 (p-value = 0.001) in the whole cohort; this rise was significant from baseline-T1 (p-value < 0.001), but not from T1 to T2 (p-value = 0.842). A similar pattern was seen in the "on therapy" cohort. BECOV-2 vaccine was independently associated with higher log anti-RBD titres than BBV152 (regression coefficient: 0.41; 95 % CI: 0.10-0.73; p = 0.011). Cellular immune responses were similar in the "on-" and "off therapy" groups at the three time points. CONCLUSION: Among AYA cancer patients, a single non-mRNA vaccine dose confers robust hybrid humoral immunity with limited benefit from a second dose.

Nutritional characteristics and antiradical activity of turmeric (Curcuma longa L.), beetroot (Beta vulgaris L.), and carrot (Daucus carota L.) grown in Bangladesh.

Curcuma longa L. (turmeric), Beta vulgaris L. (beetroot), and Daucus carota L. (carrot) grown in Bangladesh were analyzed for nutritional and phytochemical contents to reveal their comparative nutritional compositions and antiradical properties. Ash, protein, and carbohydrate content were significantly preeminent in beetroot as compared to others. Whereas fat content was found to be high in turmeric, carrots contained a great percentage of crude fiber. Beetroot was shown to have much greater potassium, calcium, and iron levels than others. Regarding amino acids, glutamic acid was found to be greater in beetroot and carrot whereas turmeric had significantly high aspartic acid content. Leucine had the highest concentration among essential amino acids in these three samples. Total antioxidant activity, total flavonoids, and phenolic contents in the methanolic extract of turmeric were found to be substantially higher than in beetroot and carrot. Furthermore, the extract of turmeric (IC50 value: 13.46 µg/mL) scavenged 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) free radicals considerably to a greater extent than beetroot (IC50 value: 380.61 µg/mL) and carrot (IC50 value: 1252.85 µg/mL). A positive correlation was found between the phytochemical contents and antiradical activity. The information from this study will help to find the potential ingredients from these plants for functional food.

In silico exploration of Serratia sp. BRL41 genome for detecting prodigiosin Biosynthetic Gene Cluster (BGC) and in vitro antimicrobial activity assessment of secreted prodigiosin.

The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. "Prodigiosin NRPS", among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 µg/mL and 7.81 to 31.25 µg/mL respectively. At concentration 500 µg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 µg/mL pigment where 125 µg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections.

Nano-crystallite bones of Oreochromis niloticus and Katsuwonus pelamis for the photocatalytic degradation of Congo red dye.

The bones of two fish species, Oreochromis niloticus and Katsuwonus pelamis, were chosen in this research for evaluating their photocatalytic efficacy under solar radiation. The fish bones were isolated and conditioned before analyzing crystallographic parameters. The samples were characterized by using different instrumental techniques such as Fourier Transform Infrared (FTIR), X-ray diffraction (XRD), Energy Dispersive X-ray (EDX), Field Emission Scanning Electronic Microscopy (FESEM), and optical bandgap. From the XRD data, various types of crystallographic information such as crystallite size, microstrain, lattice parameters, dislocation density, degree of crystallinity, crystallinity index, Hydroxylapatite (HAp), the volume fraction of ß-TCP, ß-Tricalcium phosphate (ß-TCP) percentage, and specific surface area were evaluated. Different model equations such as the Sahadat-Scherrer model, Linear Straight-line model, Monshi-Scherrer's method, and Williamson-Hall plot were employed to justify the nano-crystallite size. The photocatalytic efficacy of the two types of samples was explored by changing the catalyst concentration, dye concentration, interaction time, pH of the solution, etc. under solar irradiation.

Nutritional characterization and antioxidant properties of various edible portions of Cucurbita maxima: A potential source of nutraceuticals.

Pumpkin (Cucurbita maxima) is a widely grown vegetable in Bangladesh and is known as the sole supplier of various nutrients. Many studies evidence the nutritional value of flesh and seed while peel, flower, and leaves were reported scarcely with limited information. Therefore, the study aimed to investigate the nutritional composition and antioxidant properties of flesh, peel, seed, leaves, and flowers of Cucurbita maxima. The seed had a remarkable composition of nutrients and amino acids. Flowers and leaves possessed higher content of minerals, phenols, flavonoids, carotenes, and total antioxidant activity. The order of IC50 value (peel > seed > leaves > flesh > flower) indicates higher DPPH radicals scavenging activity of the flower. Moreover, a significant positive relationship was observed among these phytochemical constituents (TPC, TFC, TCC, TAA) and DPPH radicals scavenging activity. It could be concluded that these five parts of the pumpkin plant have an intense potency to be an exigent component of functional food or medicinal herbs.

Food Color Additives in Hazardous Consequences of Human Health: An Overview.

Food color additives are used to make food more appetizing. The United States Food and Drug Administration (FDA) permitted nine artificial colorings in foods, drugs, and cosmetics, whereas the European Union (EU) approved five artificial colors (E-104, 122, 124, 131, and 142) for food. However, these synthetic coloring materials raise various health hazards. The present review aimed to summarize the toxic effects of these coloring food additives on the brain, liver, kidney, lungs, urinary bladder, and thyroid gland. In this respect, we aimed to highlight the scientific evidence and the crucial need to assess potential health hazards of all colors used in food on human and nonhuman biota for better scrutiny. Blue 1 causes kidney tumor in mice, and there is evidence of death due to ingestion through a feeding tube. Blue 2 and Citrus Red 2 cause brain and urinary bladder tumors, respectively, whereas other coloring additives may cause different types of cancers and numerous adverse health effects. In light of this, this review focuses on the different possible adverse health effects caused by these food coloring additives, and possible ways to mitigate or avoid the damage they may cause. We hope that the data collected from in vitro or in vivo studies and from clinical investigations related to the possible health hazards of food color additives will be helpful to both researchers and the food industry in the future.

Multifunctional role of natural products for the treatment of Parkinson's disease: At a glance.

Natural substances originating from plants have long been used to treat neurodegenerative disorders (NDs). Parkinson's disease (PD) is a ND. The deterioration and subsequent cognitive impairments of the midbrain nigral dopaminergic neurons distinguish by this characteristic. Various pathogenic mechanisms and critical components have been reported, despite the fact that the origin is unknown, such as protein aggregation, iron buildup, mitochondrial dysfunction, neuroinflammation and oxidative stress. Anti-Parkinson drugs like dopamine (DA) agonists, levodopa, carbidopa, monoamine oxidase type B inhibitors and anticholinergics are used to replace DA in the current treatment model. Surgery is advised in cases where drug therapy is ineffective. Unfortunately, the current conventional treatments for PD have a number of harmful side effects and are expensive. As a result, new therapeutic strategies that control the mechanisms that contribute to neuronal death and dysfunction must be addressed. Natural resources have long been a useful source of possible treatments. PD can be treated with a variety of natural therapies made from medicinal herbs, fruits, and vegetables. In addition to their well-known anti-oxidative and anti-inflammatory capabilities, these natural products also play inhibitory roles in iron buildup, protein misfolding, the maintenance of proteasomal breakdown, mitochondrial homeostasis, and other neuroprotective processes. The goal of this research is to systematically characterize the currently available medications for Parkinson's and their therapeutic effects, which target diverse pathways. Overall, this analysis looks at the kinds of natural things that could be used in the future to treat PD in new ways or as supplements to existing treatments. We looked at the medicinal plants that can be used to treat PD. The use of natural remedies, especially those derived from plants, to treat PD has been on the rise. This article examines the fundamental characteristics of medicinal plants and the bioactive substances found in them that may be utilized to treat PD.

Regulation of cell adhesion: a collaborative effort of integrins, their ligands, cytoplasmic actors, and phosphorylation.

Integrins are large heterodimeric type 1 membrane proteins expressed in all nucleated mammalian cells. Eighteen α-chains and eight ß-chains can combine to form 24 different integrins. They are cell adhesion proteins, which bind to a large variety of cellular and extracellular ligands. Integrins are required for cell migration, hemostasis, translocation of cells out from the blood stream and further movement into tissues, but also for the immune response and tissue morphogenesis. Importantly, integrins are not usually active as such, but need activation to become adhesive. Integrins are activated by outside-in activation through integrin ligand binding, or by inside-out activation through intracellular signaling. An important question is how integrin activity is regulated, and this topic has recently drawn much attention. Changes in integrin affinity for ligand binding are due to allosteric structural alterations, but equally important are avidity changes due to integrin clustering in the plane of the plasma membrane. Recent studies have partially solved how integrin cell surface structures change during activation. The integrin cytoplasmic domains are relatively short, but by interacting with a variety of cytoplasmic proteins in a regulated manner, the integrins acquire a number of properties important not only for cell adhesion and movement, but also for cellular signaling. Recent work has shown that specific integrin phosphorylations play pivotal roles in the regulation of integrin activity. Our purpose in this review is to integrate the present knowledge to enable an understanding of how cell adhesion is dynamically regulated.

Correction to: Functional Polymorphism Located in the microRNA Binding Site of the Insulin Receptor (INSR) Gene Confers Risk for Type 2 Diabetes Mellitus in the Bangladeshi Population.

The original version of this article unfortunately contained a mistake in the co-author name. It should be Farhana Jahan instead of Farhan Jahan.

Functional Polymorphism Located in the microRNA Binding Site of the Insulin Receptor (INSR) Gene Confers Risk for Type 2 Diabetes Mellitus in the Bangladeshi Population.

Bangladesh has the second largest number of adults with diabetes in South Asia. Compelling evidence suggest that miRNAs contribute to the etiology of Type 2 diabetes mellitus (T2DM) by regulating many aspects of glucose homeostasis. Hence, we hypothesized that genetic polymorphisms in the diabetes-related miRNA target-binding sites could be associated with the risk of T2DM in Bangladesh. The reference Single nucleotide polymorphism (SNP) data from the Insulin Receptor (INSR) gene were downloaded from the ENSEMBL genome browser release 88 and further analyzed in silico for identifying SNPs with deleterious effect and clinical relationships. Further, case-control study using the microRNA-binding site polymorphism rs1366600 (T > C) located at the 3' UTR of the INSR gene was carried out in 217 T2DM patients and 237 healthy controls from Bangladesh. Genotyping was performed using the real time PCR based allele discrimination method. The results showed that the minor allele 'C' is associated with increased risk of T2DM [Odds ratio (OR) 1.87; 95% confidence intervals (CI) 1.28-2.74; P = 0.0010]. When we dissected our analysis to include the dominant model (CC + TC genotype against the TT genotype), we found that the CC and TC genotypes were associated with increased risk of T2DM in Bangladeshi population (OR 2.01; 95% CI 1.31-3.07; P = 0.0012). However, in recessive model (CC vs TT + TC); the effect was not statistically significant (OR 2.23; 95% CI 0.66-7.51; P = 0.1848). Stratification of our data based on the gender of the cases and controls showed similar degree of risk association with respect to different genotypes and alleles. Our study showed that the miRNA binding site polymorphism rs1366600 located at the 3'-UTR region of the INSR gene is associated with increased risk of T2DM in Bangladeshi individuals.

Phosphorylation of the α-chain in the integrin LFA-1 enables ß2-chain phosphorylation and α-actinin binding required for cell adhesion.

The integrin leukocyte function-associated antigen-1 (LFA-1) plays a pivotal role in leukocyte adhesion and migration, but the mechanism(s) by which this integrin is regulated has remained incompletely understood. LFA-1 integrin activity requires phosphorylation of its ß2-chain and interactions of its cytoplasmic tail with various cellular proteins. The α-chain is constitutively phosphorylated and necessary for cellular adhesion, but how the α-chain regulates adhesion has remained enigmatic. We now show that substitution of the α-chain phosphorylation site (S1140A) in T cells inhibits the phosphorylation of the functionally important Thr-758 in the ß2-chain, binding of α-actinin and 14-3-3 protein, and expression of an integrin-activating epitope after treatment with the stromal cell-derived factor-1α. The presence of this substitution resulted in a loss of cell adhesion and directional cell migration. Moreover, LFA-1 activation through the T-cell receptor in cells expressing the S1140A LFA-1 variant resulted in less Thr-758 phosphorylation, α-actinin and talin binding, and cell adhesion. The finding that the LFA-1 α-chain regulates adhesion through the ß-chain via specific phosphorylation at Ser-1140 in the α-chain has not been previously reported and emphasizes that both chains are involved in the regulation of LFA-1 integrin activity.

Ethnopharmacological survey on traditional medicinal plants at Kalaroa Upazila, Satkhira District, Khulna Division, Bangladesh.

AIM: The traditional source of medicinal plants is an important way for daily curative uses in the rural area throughout Bangladesh. An ethnomedicinal survey was conducted in a randomized manner among traditional medicinal practitioners to find out about the medicinal plants of Kalaroa, Bangladesh. MATERIALS AND METHODS: The information was collected through conducting interviews, discussion, and field observations with herbal healers and knowledgeable elders of the study areas from November 01, 2015, to December 31, 2015, who pointed out various medicinal plants and described their uses, using semi-structured questionnaires. RESULTS: A total of 29 plants distributed into 21 families had found to be used by the 3 Kavirajes interviewed for the treatment of various ailments. 42 different individual sicknesses were claimed to be cured by plants mentioned by the Kavirajes. The Malvaceae family contributed the highest number of plants with four plants, followed by the Amaranthaceae family with three plants, and the Leguminosae and Euphorbiaceae families with two plants each. Leaves were the major plant parts used solely or mixed with other parts forming 33% of total users. This was followed by roots 22%, whole plant 12%, stem and bark, fruit and seeds, and flowers 10% each, and pods, rhizomes, and sap 2% each. Seven plants for skin diseases. Four plants for erectile dysfunction. Cough, diabetes, diarrhea, dysentery, and ulcer were treated by five plants each. Asthma, diuretic, and leukorrhea were treated by three plants each. Hypertension was treated by two plants. CONCLUSION: It is expected that the other plants observed to be used for the treatment of various diseases by the Kavirajes can be subjected to further bioactivity and phytochemical studies, which can lead to the discovery of newer drugs.

LFA-1 integrin antibodies inhibit leukocyte α4ß1-mediated adhesion by intracellular signaling.

Binding of intercellular adhesion molecule-1 to the ß2-integrin leukocyte function associated antigen-1 (LFA-1) is known to induce cross-talk to the α4ß1 integrin. Using different LFA-1 monoclonal antibodies, we have been able to study the requirement and mechanism of action for the cross-talk in considerable detail. LFA-1-activating antibodies and those inhibitory antibodies that signal to α4ß1 induce phosphorylation of Thr-758 on the ß2-chain, which is followed by binding of 14-3-3 proteins and signaling through the G protein exchange factor Tiam1. This results in dephosphorylation of Thr-788/789 on the ß1-chain of α4ß1 and loss of binding to its ligand vascular cell adhesion molecule-1. The results show that with LFA-1 antibodies, we can activate LFA-1 and inhibit α4ß1, inhibit both LFA-1 and α4ß1, inhibit LFA-1 but not α4ß1, or not affect LFA-1 or α4ß1 These findings are important for the understanding of integrin regulation and for the interpretation of the effect of integrin antibodies and their use in clinical applications.

Specific phosphorylations transmit signals from leukocyte ß2 to ß1 integrins and regulate adhesion.

The regulation of integrins expressed on leukocytes must be controlled precisely, and members of different integrin subfamilies have to act in concert to ensure the proper traffic of immune cells to sites of inflammation. The activation of ß2 family integrins through the T cell receptor or by chemokines leads to the inactivation of very late antigen 4. The mechanism(s) of this cross-talk has not been known. We have now elucidated in detail how the signals are transmitted from leukocyte function-associated antigen 1 and show that, after its activation, the signaling involves specific phosphorylations of ß2 integrin followed by interactions with cytoplasmic signaling proteins. This results in loss of ß1 phosphorylation and a decrease in very late antigen 4 binding to its ligand vascular cell adhesion molecule 1. Our results show how a member of one integrin family regulates the activity of another integrin. This is important for the understanding of integrin-mediated processes.

Medicinal formulations of a Kanda tribal healer--a tribe on the verge of disappearance in Bangladesh.

The Kanda tribe is one of the lesser known small tribes of Bangladesh with an estimated population of about 1700 people (according to them), and on the verge of extinction as a separate entity. To some extent, they have assimilated with the surrounding mainstream Bengali-speaking population, but they still maintain their cultural practices including traditional medicinal practices, for which they have their own tribal healers. Nothing at all has been documented thus far about their traditional medicinal practices and formulations, which are on the verge of disappearance. The Kanda tribe can be found only in scattered tea gardens of Sreemangal in Sylhet district of Bangladesh; dispersion of the tribe into small separated communities is also contributing to the fast losing of traditional medicinal practices. The objective of the present study was to conduct an ethnomedicinal survey among the traditional healers of the Kanda tribe (in fact, only one such healer was found after extensive searches). Information was collected from the healer with the help of a semi-structured questionnaire and the guided field-walk method. A total of 24 formulations were obtained from the healer containing 34 plants including two plants, which could not be identified. Besides medicinal plants, the Kanda healer also used the body hairs of the Asiatic black bear (Ursus thibetanus) and bats (Pteropus giganteus giganteus) in one of his formulation for treatment of fever with shivering. The ailments treated by the Kanda healer were fairly common ailments like cuts and wounds, skin diseases, helminthiasis, fever, respiratory problems (coughs, asthma), gastrointestinal disorders (stomach pain, constipation, diarrhea), burning sensations during urination, various types of pain (headache, body ache, toothache, ear ache), conjunctivitis, poisonous snake, insect or reptile bites, jaundice, and bone fractures. A number of important drugs in allopathic medicine like quinine, artemisinin, and morphine (to name only a few) have been discovered from observing indigenous medicinal practices. From that view point, the formulations used by the Kanda healer merit scientific studies for their potential in the discovery of cheap and effective new drugs. Scientific validation of the medicinal formulations of the Kanda healer can also be effective for treatment of ailments among this tribe, which does not have or does not want to have any contact with modern medicine.

Tribal formulations for treatment of pain: a study of the Bede community traditional medicinal practitioners of Porabari Village in Dhaka District, Bangladesh.

The Bedes form one of the largest tribal or indigenous communities in Bangladesh and are popularly known as the boat people or water gypsies because of their preference for living in boats. They travel almost throughout the whole year by boats on the numerous waterways of Bangladesh and earn their livelihood by selling sundry items, performing jugglery acts, catching snakes, and treating village people by the various riversides with their traditional medicinal formulations. Life is hard for the community, and both men and women toil day long. As a result of their strenuous lifestyle, they suffer from various types of pain, and have developed an assortment of formulations for treatment of pain in different parts of the body. Pain is the most common reason for physician consultation in all parts of the world including Bangladesh. Although a number of drugs are available to treat pain, including non-steroidal, steroidal, and narcotic drugs, such drugs usually have side-effects like causing bleeding in the stomach over prolonged use (as in the case of rheumatic pain), or can be addictive. Moreover, pain arising from causes like rheumatism has no proper treatment in allopathic medicine. It was the objective of the present study to document the formulations used by the Bede traditional practitioners for pain treatment, for they claim to have used these formulations over centuries with success. Surveys were conducted among a large Bede community, who reside in boats on the Bangshi River by Porabari village of Savar area in Dhaka district of Bangladesh. Interviews of 30 traditional practitioners were conducted with the help of a semi-structured questionnaire and the guided field-walk method. It was observed that the Bede practitioners used 53 formulations for treatment of various types of pain, the main ingredient of all formulations being medicinal plants. Out of the 53 formulations, 25 were for treatment of rheumatic pain, either exclusively, or along with other types of body pain. A total of 65 plants belonging to 39 families were used in the formulations. The Fabaceae family provided 7 plants followed by the Solanaceae family with 4 plants. 47 out of the 53 formulations were used topically, 5 formulations were orally administered, and 1 formulation had both topical and oral uses. 8 formulations for treatment of rheumatic pain contained Calotropis gigantea, suggesting that the plant has strong potential for further scientific studies leading to discovery of novel efficacious compounds for rheumatic pain treatment.

Medicinal plants and formulations used by the Soren clan of the Santal tribe in Rajshahi district, Bangladesh for treatment of various ailments.

The Santals form the largest tribal community in northern Bangladesh reside primarily in Rajshahi and Rangpur Divisions, where they live in the districts of Rajshahi, Rangpur, Thakurgaon, Dinajpur, and Panchagarh. Although they are fast losing their traditional medicinal practices, they still have their own medicinal practitioners who rely mostly on medicinal plants for treatment of a variety of ailments. The traditional medicinal practices vary quite extensively between the twelve clans of the Santals. The objective of the present study was to conduct an ethnomedicinal survey amongst the Soren clan of the Santal community residing in two villages of Tanor Santal Para in Rajshahi district to collect information on their use of medicinal plants. Interviews were conducted of the two existing Santal traditional medicinal practitioners of the Soren clan with the help of a semi-structured questionnaire and using the guided field-walk method. Plant specimens as pointed out by the practitioners were collected and pressed on the field and identification completed at the Bangladesh National Herbarium. Information on 53 medicinal plants distributed into 32 families was obtained in this survey. Ailments treated by these plants included skin disorders, respiratory tract disorders, gastro-intestinal disorders, sexual dysfunctions, sexually transmitted diseases, diabetes, helminthiasis, pain, urinary problems, filariasis, leprosy, tuberculosis, epilepsy, snake bite, enlarged heart, and paralysis. The medicinal plants used by the Santals merit further scientific studies for some of their formulations are used to treat diseases like diabetes, paralysis, enlarged heart, tuberculosis, and filariasis for which modern medicine has no known cure or medicines have developed resistant vectors.

TCR-induced activation of LFA-1 involves signaling through Tiam1.

Adhesion is pivotal for most leukocyte functions, and the ß(2) integrin family of adhesion molecules plays a central role. The integrins need activation to become functional, but the molecular events resulting in adhesion have remained incompletely understood. In human T cells, activation through the TCR results in specific phosphorylation of the T758 on the ß(2) chain of LFA-1. We now show that this phosphorylation leads to downstream binding of 14-3-3 proteins, followed by engagement of the guanine nucleotide exchange factor protein Tiam1 and Rac1 activation. Downregulation of the signaling molecules inhibits LFA-1 activity. Activation by the chemokine stromal cell-derived factor-1α also results in T758 phosphorylation and integrin activation. Thus, TCR and chemokine activation converges on LFA-1 phosphorylation, followed by similar downstream events affecting adhesion.

Interleukin 1B gene polymorphism is associated with baseline C-reactive protein levels in healthy individuals.

C-reactive protein (CRP) is a sensitive marker of inflammation induced by both IL-6 and IL-1. Thus, genetic variation in these genes could be associated with the variety in C-reactive protein levels, and therefore with the severity of the entire inflammatory response. Even a subtle elevation in baseline CRP levels in healthy individuals has been found to significantly increase the risk for cardiovascular diseases. Therefore, to find out the possible role of pro-inflammatory cytokines in CRP baseline regulation we conducted a study of 338 healthy blood donors whose CRP levels were determined and whose single nucleotide polymorphisms of IL1A(C/T)-889, IL1B(C/T)-511, IL1B(C/T) + 3954, IL6(G/C)-174 and ILRN (a VNTR) both genotyped and haplotyped. The data revealed an association between CRP levels and the IL1B + 3954 genotype. Also, the bilocus haplotype IL1B-511*1/IL1B + 3954*2 was more frequent in subjects with below median CRP levels (< 0.72 mg/l), and composite genotype analysis of IL1B-511/IL1B + 3954 supported this finding. Our findings suggest that in healthy people, basal CRP levels are regulated by IL1B but not by IL6 genetics.