A Review of Spectroscopic and Non-Spectroscopic Techniques for Diagnosing Breast Cancer.

Malignancy, one of the leading causes of death worldwide, accounts for 9.6 million deaths in 2018. Around 1 out of 6 deaths are the direct result of the malignancy. Clinicians claim that age and breast density are two preliminary factors increasing the risk of cancer. The mortality rate brought about by malignant growth in low and high income countries is, for the most part, around 70%. Imaging techniques play a vital role in the detection, and staging, thereby helping in treatment decision making. This review paper presents a comprehensive survey involving a literature study about the evolution and efficacy of various breast cancer detection techniques. This work studies various procedures of imaging techniques such as mammograms, ultrasound, MRI, PET, CT, Terahertz Spectroscopy, Raman Spectroscopy, Optical coherence Tomography, Mass spectroscopy, diffuse reflectance spectroscopy, and Infrared Thermography. Since cancer is a complicated illness with diverse pathophysiologies, numerous modifications of the fundamental detection approach employed in each of these modalities have been performed throughout the years to increase the detection efficiency. This paper covers basic preliminary results with FFPE breast cancer blocks of malignant and normal subjects using THz Techniques that are presented as proof of concept to carry out further research.

Micronutrient Deficiency in Pregnancy: Time to Think Beyond Iron and Folic Acid Supplementation.

Background: Micronutrients play an important role in influencing pregnancy outcomes. Anemia is common among pregnant women against which iron and folic acid supplementation programs are already in action. The study aimed to estimate the prevalence of anemic and selected micronutrient status among pregnant women. Materials and Methods: It is a community-based cross-sectional study. The study was carried out among pregnant women registered in Primary Health Center, Kallur, Tirunelveli district, Tamil Nadu, India, using a semi-structured data capture tool. The blood samples were collected following standard procedure. Results: The micronutrient status among 139 pregnant women were selenium <1%, copper <1%, zinc 11.5%, iodine 14.4%, Vitamin B12 41.7%, and ferritin 42.4%. Vitamin B12, zinc, and selenium levels showed a significant difference with reference values among the three trimesters. Iron and folic acid supplementation was followed by 58.7% of pregnant women. Multiple micronutrient deficiency with anemia was found among 54.6%. Conclusion: Anemia and micronutrient deficiency are high among pregnant women in this region. Since iron and folic acid supplementation strategies are already being implemented by the government, it is high time that we extend our health policy beyond that and plan for micronutrient supplementation as well.

The comparison of effects of fentanyl and dexmedetomidine as adjuvants to ropivacaine for ultrasound-guided transversus abdominis plane block for postoperative pain in cesarean section under spinal anesthesia -A randomized controlled trial.

BACKGROUND AND AIMS: Transversus abdominis plane (TAP) block has been effectively used for anterior abdominal wall analgesia. The aim of the study was to compare the duration of analgesia produced by two drugs fentanyl and dexmedetomidine as adjuvants to ropivacaine in TAP block under ultrasound-guidance after lower segment cesarean section in a randomized controlled trial. MATERIAL AND METHODS: Sixty-four women of American Society of Anaesthesiologists (ASA) physical status II coming for cesarean sections were randomized to receive TAP blocks on each side of the abdomen using the local anesthetic drug 20 ml of 0.5% ropivacaine with either fentanyl 25 mcg or dexmedetomidine 25 mcg. A ten point numerical pain score was done at baseline, at 1 h and then at intervals of 4 h postoperatively. The hemodynamic parameters such as heart rate, blood pressure, and pulse oximetry were also monitored as above. The time to first analgesia demand from the time of the block and the total analgesic consumption were recorded. The statistical analysis was done by Mann-Whitney U test and the analgesics consumption by using Chi-square test with R software. RESULTS: Our primary end-point was to assess the duration of analgesia produced by fentanyl added to ropivacaine for ultrasound-guided TAP block, which were 125 min with Q1-Q3 as 110-180 and dexmedetomidine 130 min with Q1-Q3 as 105-161 (P value = 0.47). The amount of analgesics used in the postoperative period in both the groups were analyzed using the Chi-square test not found to have any significant difference between both the groups (P-value = 0.512). CONCLUSION: Fentanyl and dexmedetomidine as adjuvants to ropivacaine in ultrasound-guided TAP block were equally effective in both prolongation of analgesia and reducing the total consumption of analgesics.

Delivering an Integrated Package of Maternal Nutrition Services in Andhra Pradesh and Telangana (India).

BACKGROUND: Maternal spot feeding programs operational in southern Indian States are providing a package of nutrition services (food, micronutrient supplementation, deworming, gestation weight gain monitoring, and fortnightly nutrition health education) to pregnant women. These remain to be evaluated. OBJECTIVE: We evaluated the maternal spot feeding programs in 2 Southern Indian states. METHODS: Study design was cross-sectional entailing primary data collection (July to November 2016) on 360 pregnant and lactating women (of infants aged 0-6 months) per state and a review of the scheme's management information system (MIS) beneficiaries' records for the time period April 2014 to August 2017. To gain program functioning insights, open-ended interviews (n = 252) with state, district, and block program managers a state-level open space technology workshop was conducted. RESULTS: Average days of meal consumption ranged from 19 to 21 days per month; spot meal enhanced high dietary diversity (≥6 food groups; 57%-59%) and consumption of eggs and milk (74%-96%) among pregnant and lactating women. On-the-spot consumption of iron, folic acid, calcium, and deworming was 18%, 87%, and 56%, respectively; 94% attended at least 1 of the 2 nutrition monthly counseling sessions. Majority (68%) of the beneficiaries were motivated to enroll by self-help groups or family members, suggesting the crucial persuasive role of peers and family members. CONCLUSION: Maternal spot feeding schemes can potentially deliver nutrition interventions outlined in the World Health Organization antenatal care guidelines 2016 for a positive pregnancy outcome. Research on schemes' impact on birth outcomes, maternal depression, social norms, and its cost-effectiveness is needed.

Red Cell Storage Duration Does Not Affect Outcome after Massive Blood Transfusion in Trauma and Nontrauma Patients: A Retrospective Analysis of 305 Patients.

BACKGROUND: Prolonged storage of packed red blood cells (PRBCs) may increase morbidity and mortality, and patients having massive transfusion might be especially susceptible. We therefore tested the hypothesis that prolonged storage increases mortality in patients receiving massive transfusion after trauma or nontrauma surgery. Secondarily, we considered the extent to which storage effects differ for trauma and nontrauma surgery. METHODS: We considered surgical patients given more than 10 units of PRBC within 24 hours and evaluated the relationship between mean PRBC storage duration and in-hospital mortality using multivariable logistic regression. Potential nonlinearities in the relationship were assessed via restricted cubic splines. The secondary hypothesis was evaluated by considering whether there was an interaction between the type of surgery (trauma versus nontrauma) and the effect of storage duration on outcomes. RESULTS: 305 patients were given a total of 8,046 units of PRBCs, with duration ranging from 8 to 36 days (mean ± SD: 22 ± 6 days). The odds ratio [95% confidence interval (CI)] for in-hospital mortality corresponding to a one-day in mean PRBC storage duration was 0.99 (0.95, 1.03, P = 0.77). The relationship did not differ for trauma and nontrauma patients (P = 0.75). Results were similar after adjusting for multiple potential confounders. CONCLUSIONS: Mortality after massive blood transfusion was no worse in patients transfused with PRBC stored for long periods. Trauma and nontrauma patients did not differ in their susceptibility to prolonged PRBC storage.

Propensity of crocin to offset Vipera russelli venom induced oxidative stress mediated neutrophil apoptosis: a biochemical insight.

Viper envenomation results in inflammation at the bitten site as well as target organs. Neutrophils and other polymorphonuclear leukocytes execute inflammation resolving mechanism and will undergo apoptosis after completing the task. However, the target specific toxins induce neutrophil apoptosis at the bitten site and in circulation prior to their function, thus reducing their number. Circulating activated neutrophils are major source of inflammatory cytokines and leakage of reactive oxygen species (ROS)/other toxic intermediates resulting in aggravation of inflammatory response at the bitten/target site. Therefore, neutralization of venom induced neutrophil apoptosis reduces inflammation besides increasing the functional neutrophil population. Therefore, the present study investigates the venom induced perturbances in isolated human neutrophils and its neutralization by crocin (Crocus sativus) a potent antioxidant carotenoid. Human neutrophils on treatment with venom resulted in altered ROS generation, intracellular Ca(2+) mobilization, mitochondrial membrane depolarization, cyt-c translocation, caspase activation, phosphatidylserine externalization and DNA damage. On the other hand significant protection against oxidative stress and apoptosis were evidenced in crocin pre-treated groups. In conclusion the viper venom induces neutrophil apoptosis and results in aggravation of inflammation and tissue damage. The present study demands the necessity of an auxiliary therapy in addition to antivenin therapy to treat secondary/overlooked complications of envenomation.

Development, evaluation, and influence of formulation and process variables on in vitro performance of oral elementary osmotic device of atenolol.

PURPOSE: Osmotic devices are the most promising strategy-based systems for controlled drug delivery. By optimizing formulation and processing parameters, possible to develop osmotic systems to deliver drugs at predetermined rate with high in vitro-in vivo correlation. The aim of the present investigation was to develop an oral elementary osmotic pump (EOP) of atenolol with zero-order or near zero-order drug release profile. MATERIALS AND METHODS: Differential scanning calorimetry and Fourier transform-infrared spectroscopy studies did not show any evidence of interaction between the drug and excipients. Formulations were prepared by wet granulation method and coated with cellulose acetate (CA)/ethyl cellulose containing varying amounts of dibutyl phthalate (DBP)/poly (ethylene glycol)-400 as a plasticizer. The effect of different formulation variables on drug release: type and concentration of osmogen and plasticizer, size of the delivery orifice, nature of the rate controlling membrane, and membrane weight gain were studied. The release studies also compared with marketed immediate release formulation. RESULTS: Formulations containing NaCl, mannitol, and combination of both as osmogens in the drug:osmogen ratio of 1:3 and 1:4 showed zero-order drug release. Marketed tablet releases more than 95% drug in different media in 90 min. The 4% CA in acetone with DBP as a plasticizer (at a concentration of 15% w/w of polymer), with orifice diameter 565 µm, and 8.05% increase in weight on coating were found to control the drug release independent of pH and agitational intensity. The formulations were stable for 3 months as per the International Council for Harmonisation guidelines. CONCLUSION: Atenolol containing EOPs and process parameters on release studies were studied and confirmed based on osmotic technology.

Lipoma or hemangioma: A diagnostic dilemma?

Lipomas and hemangiomas are well-known benign lesions of the body. However, their occurrence in the oral cavity is rare. Lipoma accounts for 1-4% of benign neoplasms of mouth affecting predominantly the buccal mucosa, floor of mouth and tongue. Hemangiomas occur mostly on the lips, buccal mucosa, tongue, and palate. Lipomas when superficially placed show yellowish surface discoloration and hemangiomas usually have reddish blue to deep blue color. Here, we report an unusual case of benign tumor occurring in the buccal vestibule.

Inflammation and oxidative stress in viper bite: an insight within and beyond.

Though systemic and local manifestations of snakebite are considered serious, the relevance of oxidative stress in viper bite pathology is largely denied. However, over the past decade, studies have provided substantial evidence for the presence of persistent oxidative stress in viper bite victims. This review aims at highlighting the disturbances in redox homeostasis soon after viper envenomation and its implications in the pathomechanism of secondary/long term complications including thrombocytopenia, hypopituitarism, infertility, renal abnormalities and persistent local tissue degradation. Both enzymatic and non-enzymatic components of viper venom play a pivotal role in bringing redox turbulence in victims. Venom-induced hemorrhage and necrosis with subsequent release of damage associated molecular pattern (DAMPs) molecules also contribute to sustained oxidative stress and inflammation. Studies have demonstrated that along with anti-venom therapy an antioxidant treatment during the early stages of viper bite and also long term treatment could help to reduce the occurrence of secondary/long term complications. Further, proper knowledge regarding the pathophysiology will allow for exploration of new avenues in the treatment of viper bite.

Melatonin alleviates Echis carinatus venom-induced toxicities by modulating inflammatory mediators and oxidative stress.

Viper bites cause high morbidity and mortality worldwide and regarded as a neglected tropical disease affecting a large healthy population. Classical antivenom therapy has appreciably reduced the snakebite mortality rate; it apparently fails to tackle viper venom-induced local manifestations that persist even after the administration of antivenom. Recently, viper venom-induced oxidative stress and vital organ damage is deemed as yet another reason for concern; these are considered as postmedicated complications of viper bite. Thus, treating viper bite has become a challenge demanding new treatment strategies, auxiliary to antivenin therapy. In the last decade, several studies have reported the use of plant products and clinically approved drugs to neutralize venom-induced pharmacology. However, very few attempts were undertaken to study oxidative stress and vital organ damage. Based on this background, the present study evaluated the protective efficacy of melatonin in Echis carinatus (EC) venom-induced tissue necrosis, oxidative stress, and organ toxicity. The results demonstrated that melatonin efficiently alleviated EC venom-induced hemorrhage and myonecrosis. It also mitigated the altered levels of inflammatory mediators and oxidative stress markers of blood components in liver and kidney homogenates, and documented renal and hepatoprotective action of melatonin. The histopathology of skin, muscle, liver, and kidney tissues further substantiated the overall protection offered by melatonin against viper bite toxicities. Besides the inability of antivenoms to block local effects and the fact that melatonin is already a widely used drug promulgating a multitude of therapeutic functionalities, its use in viper bite management is of high interest and should be seriously considered.

Bullous Lichen Planus treated with Oral Minipulse Therapy: A Rare Case Report.

Oral Lichen planus (OLP) is a common mucocutaneous disorder with a multifactorial aetiology, affecting the women more commonly than men. Most OLP are asymptomatic, except the atrophic and erosive forms.Till date many treatment modalities are implicated to treat this disorder, but no therapy is considered as the single most effective, without side-effects and remission of the lesion. As the treatment of OLP is challenging to the oral practitioners, here we report a case of successful management of extensive, symptomatic bullous and erosive oral lichen planus with a novel treatment protocol- oral minipulse therapy with betamethasone.

Sesamol ameliorates cyclophosphamide-induced hepatotoxicity by modulating oxidative stress and inflammatory mediators.

In current scenario of human health and diseases, drug-induced hepatic injury has been recognized as a serious and unresolved problem. Particularly, chemotherapeutic agents have been reported to induce organ toxicity. The aim of the present study is to evaluate organ toxicity and oxidative damage induced by cyclophosphamide (CP), a chemotherapeutic drug and its amelioration by sesamol, an antioxidant from sesame seeds. CP (150 mg/kg) is injected intraperitonially to experimental rats and from day 2 rats were orally treated with sesamol. Rats were sacrificed to evaluate non-enzymatic and enzymatic oxidative stress parameters in serum and tissue homogenates on day 8. Besides, liver function parameters and pro-inflammatory mediators were assessed. Histopathological studies of liver and kidney were also carried out. Elevated levels of endogenous reactive oxygen species, lipid peroxidation and decreased levels of glutathione, total thiols, along with the reduction in antioxidant enzymes including superoxide dismutase, catalase, glutathione-stransferase and glutathione peroxidase, were evident in CP-intoxicated animals. Pro-inflammatory mediators like tumor necrosis factor - α, interleukin (IL)-1ß, IL-6 and cyclooxygenase-2 were also elevated. Moreover, the levels of liver function markers like serum alanine aminotransferase and aspartate aminotransferase were also altered. Histology of liver and kidney tissues further supported CP-induced organ damage. Altered parameters were significantly restored to normal by oral administration of sesamol (50 mg/kg) suggesting its antioxidative stress, anti-inflammatory and hepatoprotective abilities. The study clearly demonstrated the potentiality of sesamol against CPinduced organ toxicity and oxidative stress suggesting its applicability in treatment regime of cancer and other stress-associated disorders as a supportive/auxiliary therapy.

Sesamol induces apoptosis in human platelets via reactive oxygen species-mediated mitochondrial damage.

Platelets play an indispensable role in human health and disease. Platelets are very sensitive to oxidative stress, as it leads to the damage of mitochondrial DNA, which is the initial step of a sequence of events culminating in the cell death through the intrinsic pathway of apoptosis. Owing to a lot of reports on secondary complications arising from oxidative stress caused by therapeutic drug overdose, the present study concentrated on the influence of sesamol on oxidative stress-induced platelet apoptosis. Sesamol, a phenolic derivative present in sesame seeds is an exceptionally promising drug with lots of reports on its protective functions, including its inhibitory effects on platelet aggregation at concentrations below 100 µM, and its anti-cancer effect at 1 mM. However, the present study explored the toxic effects of sesamol on human platelets. Sesamol at the concentration of 0.25 mM and above induced platelet apoptosis through endogenous generation of ROS, depletion of thiol pool, and Ca(2+) mobilization. It also induced mitochondrial membrane potential depolarization, caspase activation, cytochrome c translocation and phosphatidylserine exposure, thus illustrating the pro-apoptotic effect of sesamol at higher concentration. However, even at high concentration of 2 mM sesamol effectively inhibited collagen/ADP/epinephrine-induced platelet aggregation. The study demonstrates that even though sesamol inhibits platelet aggregation, it has the tendency to elicit platelet apoptosis at higher concentrations. Sesamol has a potential as thrombolytic agent, nevertheless the current work highlights the significance of an appropriate dosage of sesamol when it is used as a therapeutic drug.

Viper venom-induced oxidative stress and activation of inflammatory cytokines: a therapeutic approach for overlooked issues of snakebite management.

BACKGROUND AND OBJECTIVE: The snakebite mortality rate has been significantly reduced due to effective anti-venin therapy. The intravenously infused anti-venom will neutralize free and target-bound toxins but fails to neutralize venom-induced inflammation and oxidative stress, as the antigen-antibody complex itself is pro-inflammatory. Therefore, an auxiliary therapy is necessary to treat secondary/overlooked envenomation complications. MATERIALS AND METHODS: Blood samples from healthy donors were treated with viper venom (100 µg/ml) for 2 h. The venom-induced inflammation, oxidative damage and effect of crocin pre-treatment were determined by assessing the serum levels of cytoplasmic, lysosomal and oxidative stress markers along with pro-inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and cyclo-oxygenase (COX)-2. RESULTS: Significantly increased stress markers, cytoplasmic, lysosomal and extracellular matrix-degrading enzymes as well as the pro-inflammatory mediators TNF-α, IL-1ß, IL-6 and COX-2 indicated increased cellular damage but significantly reduced oxidative damage and inflammation in crocin pre-treated groups. CONCLUSION: The data clearly suggest that venom-induced oxidative stress and inflammation is also responsible for oxidative burst and cell death in the circulation, which may worsen even after anti-venin therapy. Hence, the current study demands a supportive therapy in addition to anti-venin therapy to neutralize the overlooked issues of snakebite.

Antiarthritic and antiinflammatory propensity of 4-methylesculetin, a coumarin derivative.

Coumarins are a group of natural compounds widely distributed in plants. Of late, coumarins and their derivatives have grabbed much attention from the pharmacological and pharmaceutical arena due to their broad range of therapeutical qualities. A coumarin derivative 4-methylesculetin (4-ME) has known to possess effective antioxidant and radical-scavenging properties. Recently they have also shown to down regulate nuclear factor-kappa B (NF-κB) and protein kinase B (Akt) that play a vital role in inflammation and apoptosis. In view of this, the present study investigated the anti-arthritic potentiality of 4-ME by assessing its ability to inhibit cartilage and bone degeneration, inflammation and associated oxidative stress. Arthritis being a debilitating joint disease, results in the deterioration of extracellular matrix (ECM) of cartilage and synovium. Participation of both enzymatic and non-enzymatic factors in disease perpetuation is well documented. The present study demonstrated the mitigation of augmented serum levels of hyaluronidase and matrix metalloproteinases (MMP-13, MMP-3 and MMP-9) responsible for cartilage degeneration by 4-ME. It also protected bone resorption by reducing the elevated levels of bone-joint exoglycosidases, cathepsin-D and tartrate resistant acid phosphatases. Further, 4-ME significantly ameliorated the upregulated non-enzymatic inflammatory markers like TNF-α, IL-1ß, IL-6, COX-2 and PGE2. Besides, 4-ME effectively stabilized the arthritis-induced oxidative stress by restoring the levels of reactive oxygen species, lipid and hydro peroxides and antioxidant enzymes such as superoxide dismutase, catalase and glutathione-S-transferase. Thus, the study suggests that 4-ME could be an effective agent to treat arthritis and associated secondary complications like oxidative stress.

N-Acetylcysteine amide: a derivative to fulfill the promises of N-Acetylcysteine.

In the present human health scenario, implication of oxidative stress in numerous pathologies including neurodegenerative, cardiovascular, liver, renal, pulmonary disorders, and cancer has gained attention. N-Acetylcysteine (NAC), a popular thiol antioxidant, has been clinically used to treat various pathophysiological disorders. However, NAC therapy is routine only in paracetamol intoxication and as a mucolytic agent. Over six decades, numerous studies involving NAC therapy have yielded inconsistent results, and this could be due to low bioavailability. In order to overcome the limitations of NAC, an amide derivative N-Acetylcysteine amide (NACA) has been synthesized to improve the lipophilicity, membrane permeability, and antioxidant property. Recent studies have demonstrated the blood-brain barrier permeability and therapeutic potentials of NACA in neurological disorders including Parkinson's disease, Alzheimer's disease, Multiple sclerosis, Tardive dyskinesia, and HIV-associated neurological disorders. In addition, NACA displays protective effect against pulmonary inflammation and antibiotic-induced apoptosis. Forthcoming research on the possible therapeutic properties of NACA and its generics in the management of pathologies associated with extracellular matrix degradation and oxidative stress-related inflammation is highly exiting. Superior bioavailability of NACA is likely to fulfill the promises of NAC as well as a molecule to improve the endurance and resident time of bioscaffolds and biomaterials. Till date, more than 800 reviews on NAC have been published. However, no comprehensive review is available on the therapeutic applications of NACA. Therefore, the current review would be the first to emphasize the therapeutic potentials of NACA and its derivatives.

Alleviation of viper venom induced platelet apoptosis by crocin (Crocus sativus): implications for thrombocytopenia in viper bites.

Viper envenomations are characterized by prominent local and systemic manifestations including hematological alterations. Snake venom metalloproteinases (SVMPs) and phospholipase A2 (PLA2) plays crucial role in the pathophysiology of hemorrhage by targeting/altering the platelets function which may result in thrombocytopenia. Platelets undergo the classic events of mitochondria-mediated apoptotic pathway due to augmented endogenous reactive oxygen species (ROS) levels. The observed anticoagulant effects during viper envenomations could be due to exacerbated platelet apoptosis and thrombocytopenia. Moreover, antivenin treatments are ineffective against the venom-induced oxidative stress; therefore, it necessitates an auxiliary therapy involving antioxidants which can effectively scavenge the endothelium-generated/endogenous ROS and protect the platelets. The present study explored the effects of viper venom on platelet apoptosis and its amelioration by a phytochemical crocin. The study evaluated the Vipera russelli venom-induced apoptotic events including endogenous ROS generation, intracellular Ca(2+) mobilization, mitochondrial membrane depolarization, cyt-c translocation, caspase activation and phosphatidylserine externalization which were effectively mitigated when the venom was pre-treated with crocin. The study highlights one of the less studied features of venom-induced secondary complications i.e. platelet apoptosis and sheds light on the underlying basis for venom-induced thrombocytopenia, systemic hemorrhage and in vivo anticoagulant effect.

Inhibition of hyaluronidase by N-acetyl cysteine and glutathione: role of thiol group in hyaluronan protection.

Hyaluronidase inhibitors have immense applications in pathophysiological conditions associated with hyaluronan-hyaluronidase system. The present study demonstrates the inhibitory efficacy of clinically accepted antioxidant N-acetyl cysteine (NAC) against hyaluronidase of serum, testis, and snake and bee venoms. The experimental and molecular dynamic simulation data suggest the non-competitive inhibition and involvement of thiol groups of both NAC and glutathione in exertion of inhibition. The bioavailability, less-toxic and antioxidant nature of NAC and glutathione could become valuable in the management of pathologies triggered by extracellular matrix degradation and to increase the endurance of hyaluronan based biomaterials/supplements, which are highly exciting aspects.

A large-scale evaluation of computational protein function prediction.

Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment. Fifty-four methods representing the state of the art for protein function prediction were evaluated on a target set of 866 proteins from 11 organisms. Two findings stand out: (i) today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is considerable need for improvement of currently available tools.

Snake venom induced local toxicities: plant secondary metabolites as an auxiliary therapy.

Snakebite is a serious medical and socio-economic problem affecting the rural and agricultural laborers of tropical and sub-tropical region across the world leading to high morbidity and mortality. In most of the snakebite incidences, victims usually end up with permanent tissue damage and sequelae with high socioeconomic and psychological impacts. Although, mortality has been reduced markedly due to anti-venom regimen, it is associated with several limitations. Snake venom metalloprotease, hyaluronidase and myotoxic phospholipase A2 are the kingpins of tissue necrosis and extracellular matrix degradation. Thus, inhibition of these enzymes is considered to be the rate limiting step in the management of snakebite. Unfortunately, tissue necrosis and extracellular matrix degradation persists even after the administration of anti-venom. At present, inhibitors from snake serum and plasma, several synthetic compounds and their analogs have been demonstrated to possess anti-snake venom activities, but the use of plant metabolites for this purpose has an added advantage of traditional knowledge and will make the treatment cheaper and more accessible to the affected population. Therefore, the clinical and research forums are highly oriented towards plant metabolites and interestingly, certain phytochemicals are implicated as the antibody elicitors against venom toxicity that can be exploited in designing effective anti-venoms. Based on these facts, we have made an effort to enlist plant based secondary metabolites with antiophidian abilities and their mechanism of action against locally acting enzymes/toxins in particular. The review also describes their functional groups responsible for therapeutic beneficial and certainly oblige in designing potent inhibitors against venom toxins.