Acute and Sub-Chronic Toxicity Evaluation of the Crude Methanolic Bark Extract of Bridelia micrantha (Hochst.) Baill. (Phyllanthaceae) and Its Fraction

Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of the stem bark of Bridelia micrantha using column chromatographic techniques. The fraction F6 was the most active when tested for antibacterial activity. Thus, toxicity of this fraction was investigated for further use. The present study evaluated the acute and sub-chronic toxicity of the crude methanolic bark extract of Bridelia micrantha and its fraction. The acute toxicity was carried out according to the experimental protocol of Organization for Economic Co-operation and Development (OECD). The plant extract or the fraction F6 was administered orally to female mice at a single dose of 2000 mg/kg and the animals were observed for any behavioral changes or mortality for 14 days. In the sub-chronic toxicity study, the extract and fraction were administered orally at 200, 400 and 800 mg/kg bw/day for 28 days to healthy Wistar rats. The general behavior and body weight of the rats were recorded daily. At the end of the experimental period, hematological and biochemical analyses, changes in vital organ weight (liver, lung, heart, spleen and kidney), and histopathological examination of the liver and kidney were performed. No mortality or adverse effects were noted at the 2000 mg/kg dose during the oral acute toxicity test. In the sub-chronic study, the crude methanolic bark extract of Bridelia micrantha and the fraction F6 induced no mortality or treatment-related adverse effects on body weight, general behavior, relative organ weights, hematological and biochemical parameters. Histopathological examination of the liver and kidney showed normal architecture suggesting no morphological alterations. In conclusion, the oral administration of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 for 28 days at a dosage of up to 800 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 was estimated to be more than 2000 mg/kg.

Acute and Sub-chronic Toxicity of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br. in Beagle Dogs

Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establish the toxicity profile of the alkaloid extract(TA)of A.scholaris leaves in non-rodents.After oral administration of a single dose(4 g/kg.bw),a num-ber of transient symptoms,such as unsteady gait,drooling,emesis,and reddening of peri-oral mucosa,were observed,but no treatment-related mortality.A sub-chronic toxicity study with a range of doses of TA(20,60 and 120 mg/kg.bw)was conducted for a 13-week treatment period,followed by 4-week recovery observation.Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group,no clinical changes were observed in TA-treated animals.Data from electrocardiography,bone marrow,urine,fecal,hematology and clinical chemistry analyses were comparable between TA-treated and control animals.No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups.Accordingly,the non-observed-adverse-effect-level(NOAEL)of TA was established as 120 mg/kg.bw.Our results add further knowledge to the safety database for indole alkaloid extracts from A.scholaris with potential utility as novel drug candidates.

Sub-chronic Toxicity Test of Tephrosia canadida DC. in Mice

[ Objective] To observe sub-chronic toxicity of Tephrosia canadida DC. in mice and thus to evaluate their safety to be used as protein feed resources. [ Methed]Sixty-four 6-week-old healthy Kunming mice weighing about 25 g were randomly divided into four groups （ n = 16）, half male and half female. Mass ratios of basic diet to leaf meal of Tephrosia canadida DC. in group A, group B, group C and group D were 10：0, 4：1, 3：2 and 2：3, respectively. After 35-d feeding, the effects of Tephrosia canadida DC. on growth, blood and organs of mice were observed. [ Resultl Dudng the trial, all mice had normal activities, and no death and no abnormal blood index were observed. All organs of the mice in the experimental groups had no visible pathological lesion, and organ indexes had no significant difference between the experimental groups and the control group. Except that slightly abnormal histological changes appeared in liver and kidney of the mice in the group C and D, no histological change was ob- served in other organs of the experimental mice. [ Conclusion] Tephrosia canadida DC. have no adverse effects on mice, which provides a refer- ence for research about their safety in feed of other animals.

Preliminary studies of acute and sub-chronic toxicity of the aqueous extract of Guibourtia tessmannii(Harms) J.Leonard stem barks (Caesalpiniaceae) in mice and rats

Objective: To investigate the toxicity of aqueous extract of Guibourtia tessmannii(Harms) J. Leonard(G. tessmannii) and evaluate its safety.Methods: NMRI mice were used to determine the acute toxicity of G. tessmannii.Increasing concentrations of the plant extracts were administered intraperitoneally or by force-feeding. General behavior and death were monitored and recorded daily for 7 days.In order to determine the sub-acute toxicity of the extract, several doses were administered by oral gavage daily for 28 days in adult Wistar rats. Different parameters were assessed including body weight, food and water intake, biochemical parameters and several vital organ weights.Results: LD50 of 328.78 mg/kg was obtained by i.p. route and more than 5 000 mg/kg was obtained in acute toxicity by oral route. In sub-acute toxicity, no significant alteration was observed in body weight or vital organs, food and water intake, and biochemical parameters.Conclusions: The results showed that the aqueous extract of G. tessmannii has low toxicity intraperitoneally and no sub-acute toxicity via oral intake.

Sub-chronic Toxicity of Defoamer Used in Seawater Desalination

Objective To explore the possible long‐term health effects of the defoamer used in seawater desalination by sub‐chronic toxicity testing. Methods Blood analysis, internal organ assessment, and histopathological examination were carried out in rats exposed to low, medium, and high(0.5, 1.0, and 2.0 g/kg BW, respectively) doses of defoamer for 90 days through oral administration. Results The high dose group showed decreased blood alanine aminotransferase and aspartate aminotransferase(P < 0.05). All doses resulted in a significant increase in albumin and decrease in globulin(P < 0.05). The direct bilirubin and indirect bilirubin were decreased in the medium and high dose groups(P < 0.05). All dose groups showed significant induction of alkaline phosphatase(P < 0.05). Pathological examination revealed a case of liver mononuclear cell infiltration in the medium dose group and three cases of liver congestion, steatosis of hepatic cells around the central vein, and punctate necrosis with multiple focal mononuclear cell infiltration in male rats administered the high dose. The No Observed Adverse Effect Level was 0.5 g/kg BW in rats, with albumin and total bilirubin as health effect indices. Conclusion Long‐term defoamer exposure may cause liver injury but has no significant impact on renal function in rats. The effect on blood cells in female rats was more prominent than that in male rats.

Acute and Sub-chronic Toxicity of Tetrandrine in Intravenously Exposed Female BALB/c Mice

Objective： To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine（TET） in female BALB/c mice. Methods： The median lethal dose（LD_（50）） of intravenously administered TET was calculated in mice using Dixon＇s up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET（30, 90 and 150 mg/kg） each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. Result： LD_（50） was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically significant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET（P〉0.05）. In the sub-acute toxicity study, no significant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group（P〉0.05）, however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. Conclusions： The overall findings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.

Antimicrobial Activities of Extracts of Macrosphyra longistyla against Gram-Positive Oral Biofilm-Formers from School Children in Southwestern Nigeria and Toxicity Studies Using Brine Shrimps

The world will benefit from more effective antimicrobial agents against oral conditions arising from the actions of biofilm forming bacteria. Also, information is lacking on the oral biofilm-forming bacterial diversity in Southwestern Nigeria. In this study, we isolate and characterize oral biofilm producing bacteria in the oral cavities of schoolchildren in Southwestern Nigeria. We also investigate the antimicrobial properties of Macrosphyra longistyla extracts against the biofilm-formers and the toxicity of potent extracts. Samples were obtained from 109 schoolchildren aged 4 - 14 years from Lagos, Oyo and Osun States. Agar well diffusion technique was used in the antimicrobial susceptibility testing. Toxicity testing was done using brine shrimps (Artemia salina). Biofilm-formers in this study are Klebsiella sp., Streptococcus sp., Staphylococcus sp., and Micrococcus sp. Ethanol leaf extracts had the highest activity against all biofilm-producing bacteria. Ethanol stem bark extract, which elicited activity against Klebsiella only, was found to be less toxic than the ethanol leaf extract. Staphylococcus showed >10 mm susceptibility to the ethanol and aqueous extracts of Macrosphyra longistyla. Streptococcus and Micrococcus were susceptible to the antimicrobial actions of the ethanolic leaf extracts. Although the ethanol extracts of the leaves had lower minimum inhibitory concentrations than the ethanol extracts of the stem bark, toxicity studies showed ethanol extracts of the stem-bark to be more toxic than the ethanol extracts of the leaves. In conclusion, ethanolic extracts of Macrosphyra longistyla show potential as sources of antimicrobials against gram-positive, oral biofilm-forming bacteria.

Evidence-Based Nursing Practice of Reducing Immune-Related Skin Toxicity of Tumor Patients Guided by Sensitive Indicators

Purpose research on nursing sensitive indicators in tumor Patients application effect in immune-related skin toxicity management. Method select our hospital April to June, 202360 cases patients with immune therapy settings as the control group. August-October, 2023 60 cases the patients treated with immune therapy were the experimental group. The control group adopted regular nursing methods, while the experimental group sensitive Indicators, evidence-based give preventive care. The social situation, psychological state, physical function, quality of life score, incidence of skin toxicity caused by immune checkpoint inhibitors, moderate and above of the two groups of patients were compared. Incidence of skin toxicity. Result: experience group SAS score, SDS score higher than the control group, the difference was statistically significant (P < 0.05);The incidence of skin toxic reactions caused by immune checkpoint inhibitors and the incidence of moderate and above skin toxic reactions in the experimental group are lower than those in the control group, and the difference is statistically significant (P < 0.05). Conclusion: sensitive indicator guidance evidence-based preventive care can reduce the degree of immune-related skin toxicity, improve the psychological state and quality of life of tumor patients treated with immune therapy and reduce the incidence of adverse reactions, improve nursing quality and patient satisfaction.

Skin Toxicity of Wufang Babu Ointment to Zebrafish

[Objectives]Using wild-type AB strain of zebrafish as experimental animal,this study investigated the damaging effect of Wufang Babu Ointment on skin cells,in order to evaluate the skin toxicity of Wufang Babu Ointment.[Methods]Wild-type AB strain of zebrafish with an age of 2 d were taken and fed in different concentrations of Wufang Babu Ointment solution for 24 h.The number of deaths in each group of zebrafish was recorded,and the mortality rate was calculated.Using Origin 8.0 software,the maximum non lethal concentration(MNLC)was simulated.Zebrafish raised in different concentrations of Wufang Babu Ointment solution for 24 h were placed under an anatomical microscope for taking photos,to analyze and calculate the incidence of skin damage in zebrafish.Based on the statistical analysis results of this indicator,the skin toxicity of Wufang Babu Ointment was evaluated.[Results]The MNLC of Wufang Babu Ointment on zebrafish was 671μg/mL;Wufang Babu Ointment can induce skin damage at the concentrations of 224μg/mL(1/3 MNLC)and 671μg/mL(MNLC).[Conclusions]Wufang Babu Ointment had certain skin toxicity to zebrafish.

A therapeutic potentiality and toxicity concern of nutrient plant Annona squamosa Linn.

Annona squamosa Linn.fruit is famous for its nutritional value with a long history of medicinal benefits due to the presence of many phytochemicals,including alkaloids,diterpenes,essential oil,phytopeptides,etc.Several studies envisaged that Annona squamosa possesses cytotoxic,diuretic,antiurolithiatic,antitumor,anti-psoriatic,antioxidant,and hepatoprotective properties.This plant is traditionally used for the treatment of wound infection,dysentery,seizure,tumors,fever,vomiting,parasitic infections,hypertension,thyroid,toothache,acne,heart disease,inflammation,diabetes,hair loss,dandruff,hemorrhage,maggot-infected sores,abortifacient,and cough.However,some chemical constituents isolated from the plant have shown specific toxic effects in human and animal models,such as acute oral toxic effects,genotoxic,neurotoxic,and ocular toxic.The plant has diverse pharmacological actions,the seeds of this plant possess a genotoxic effect but on the contrary,the bark of the plant shows genoprotective activity.A large number of ethnobotanical studies reported the seed of this plant is used to induce abortion in humans,but a scientific study carried out in pregnant rats reported aqueous seed extract of the plant did not interfere with reproductive performance.The presented review summarized the traditional uses,pharmacological,and toxicological activities of the isolated compounds from this plant.Additionally,some patents and commercial products related to Annona squamosa are also brought up in this article to explore its application which would attract the scientific community to search out its hidden side.

5-Bromo-2'-deoxyuridine labeling:historical perspectives,factors infiuencing the detection,toxicity,and its implications in the neurogenesis

The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating DNA.BrdU labeling is widely used for identifying neuron precursors and following their fate during the embryonic,perinatal,and adult neurogenesis in a variety of vertebrate species including birds,reptiles,and mammals.Due to BrdU toxicity,its incorporation into replicating DNA presents adverse consequences on the generation,survival,and settled patterns of cells.This may lead to false results and misinterpretation in the identification of proliferative neuroblasts.In this review,I will indicate the detrimental effects of this nucleoside during the development of the central nervous system,as well as the reliability of BrdU labeling to detect proliferating neuroblasts.Moreover,it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal,perinatal,and adult neurogenesis.Human adult neurogenesis will also be discussed.It is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.

Changes in acute and late toxicity and patient-reported health-related quality of life following radiotherapy in women with breast cancer:A 1-year longitudinal study

Objective:The objective of this study was to investigate the frequency of acute and late toxicities,as well as changes in the quality of life(QOL)for breast cancer patients following radiotherapy(RT).Materials and Methods:A total of 108 breast cancer women were recruited for this prospective study.Data were collected at various intervals;prior to,and 1,3,6 months,and 1 year after radiation therapy.The primary outcomes were toxicity radiation therapy oncology group/European Organization for Research and Treatment of Cancer(EORTC)criteria.Our secondary outcome was QOL,measured using EORTC QLQ-C30 and Edmonton Symptom Assessment Scale.We employed Friedman’s two-way analysis to evaluate the changes in QOL over the course of 1 year.Results:The early toxicities that are most commonly experienced include pharyngeal,skin,and mucous membrane toxicity.Late toxicities frequently involve skin and submucosal toxicity.To measure patient functionality,all functional subscale scores except for the patient’s emotional state increased over time compared to pre-RT.Symptoms of the patients,which were included in the QOL symptom scale,decreased during the follow-up period,except for fatigue;however,changes in pain,insomnia,and loss of appetite did not significantly change.We identified the analogous symptom profiles in Edmonton.Although patients’overall health scores declined in the 1st and 3rd months after radiotherapy(RT),they rebounded at 6 and 12 months.Conclusion:For breast cancer patients,RT did not adversely affect functional capacity or exacerbate symptoms,but persistent fatigue did increase during the observation period.Health-care professionals ought to devise strategies to assist patients with skin toxicity and fatigue.

Improvement of Rice Plant Root by Kaolin Application in Iron Toxicity Condition at Zoukougbeu (Central-West of Côte d’Ivoire)

In the tropics, lowland rice cultivation is often confronted with the problem of iron toxicity. The solution proposed by research in general is the use of industrial silicon. However, the high cost of industrial silicon limits its adoption by farmers. A study was carried out in Zakogbeu;Center-West of Côte d’Ivoire, to assess the potential of kaolin to mitigate the effect of this soil constraint on the root of the rice plant. Five kaolin-based treatments were analyzed (T0 = 0 kg kaolin ha−1, T1 = 366 kg kaolin ha−1, T2 = 736 kg kaolin ha−1, T3 = 1097 kg kaolin ha−1 and T4 = 1465 kg kaolin ha−1 are 0, 200, 400, 600 and 800 kg SiO2 ha−1) in a device in complete random blocks, with 5 repetitions. The results obtained show that kaolin supply increases the length of the root tissue as well as the number of branching of the root of the rice plant. Root tissue increased from 10 cm with T0 treatment to more than 15 cm with treatment T4. The microscopic observation of the roots shows that in the treatment T0, the roots present only primary ramifications and the tertiary and quaternary ramifications are observed with the treatments T3 and T4. The contribution of kaolin is an alternative to inhibit the effect of iron toxicity on the rice plant root development in iron toxicity condition.

Acute Toxicity of Jinchuan Formula Plum Wine Extract and Its Protective Effect on Mice with Liver Injury

[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal dose(LD_(50))was determined by acute toxicity test with the toxic reaction and mortality of mice as indexes.Sixty Kunming mice were randomly divided into 6 groups:normal control group,model group(ConA-induced liver injury model),Jinchuan formula plum wine high,medium and low dose groups(1.0,0.5,0.25 g/kg)and silybin group(0.1 g/kg).The levels of ALT,AST,LDH in serum and TG,VLDL in liver were measured.After HE staining,the pathological changes of liver tissue in mice were observed,and the liver protective effect of Jinchuan formula plum wine extract was analyzed and evaluated.[Results]LD_(50)was 11.18 g/kg,and the 95%confidence limit of LD_(50)was 10.31-12.05 g/kg.The high-dose group of Jinchuan formula plum wine extract could significantly reduce the serum ALT and AST activities of ConA-induced liver injury mice(P<0.05).[Conclusions]Jinchuan formula plum wine extract is relatively safe,and also has a protective effect on liver injury.

Effects of Sub-chronic Intoxication of 1,8-cineole on Blood Biochemical Indexes of Mice

[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17 g were randomly divided into four groups （forty mice per group）. Mice were injected to 1, 8 - cineole with doses of 192.45,64. 15 and 21.38 mg/kg body weight （ test groups） and the water solution of tween-80 with a volume fraction of 0.5% （ control group） respectively. Each mouse was administered orally at the dose of 0.2 mL per 10 g body weight once a day consecutively for 90 d. The body weight, routine blood indexes and serum biochemical indexes of mice were determined on the 30^th d, 60^th d, 90^th d and the 30^th d after stopping the administration of 1,8-cineole. [ Result] The effects of 1, 8-cineole on the body weight, routine blood indexes and serum biochemical indexes of mice with the doses of 64.15 and 21.38 mg/kg body weight had no statistically significant difference compared with the control group （P 〉0.05 ）. 1, 8-cineole with the dose of 192.45 mg/kg body weight exhibited different influences on routine blood indexes and serum biochemical indexes of mice after the oral administration of 1,8-cineole for 60 d and 90 d, and statistically significant differences in many blood biochemical indexes were observed （P 〈 0.05 ）. However, the differences in routine blood indexes and serum biochemical indexes were not statistically significant between the test groups and the control group at the 30＇h d after stopping the administration of 1, 8-cineole （ P 〉 0.05）. [Condusion] 1,8-cineole had sub-chronic oral toxicity to mice. The no observed adverse effect level （NOAEL） of 1,8-cineolc was 64.15 mg/kg body weight and the lowest observed adverse effect level （LOAEL） of 1,8-cineole was 192.45 mg/kg body weight. Effects of 1, 8-cineole on blood biochemical indexes of mice were in short term and reversible.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Toxicity and horizontal transfer of bifenthrin and dimefluthrin against the red imported fire ant, Solenopsis invicta Buren(Hymenoptera: Formicidae), and the efficacy of their dust applications in the field

The red imported fire ant,Solenopsis invicta Buren,poses a significant threat to biodiversity,agriculture,and public health in its introduced ranges.While chemicals such as toxic baits and dust are the main methods for S.invicta control,toxic baits are slow,requiring approximately one or two weeks,but dust can eliminate the colony of fire ants rapidly in just three to five days.To explore more active ingredients for fire ant control using dusts,the toxicity of bifenthrin and dimefluthrin,the horizontal transfer of bifenthrin and dimefluthrin dust and their efficacy in the field were tested.The results showed that the LD50(lethal dose) values of bifenthrin and dimefluthrin were 3.40 and 1.57 ng/ant,respectively.The KT50(median knockdown time) and KT95(95%knockdown time) values of a 20μg mL^(–1)bifenthrin dose were 7.179and 16.611 min,respectively.The KT50and KT95of a 5μg mL^(–1)dimefluthrin dose were 1.538 and 2.825 min,respectively.The horizontal transfers of bifenthrin and dimefluthrin among workers were effective.The mortality of recipients (secondary mortality) and secondary recipients (tertiary mortality) were both over 80%at 48 h after 0.25,0.50 and 1.00%bifenthrin dust treatments.The secondary mortality of recipients was over 99%at 48 h after 0.25,0.50 and 1.00% dimefluthrin dust treatments,but the tertiary mortality was below 20%.The field trial results showed that both bifenthrin and dimefluthrin exhibited excellent fire ant control effects,and the comprehensive control effects of 1.00%bifenthrin and dimefluthrin dusts at 14 d post-treatment were 95.87 and 85.70%,respectively.

Bioengineered materials with selective antimicrobial toxicity in biomedicine

Fungi and bacteria afflict humans with innumerous pathogen-related infections and ailments.Most of the commonly employed microbicidal agents target commensal and pathogenic microorganisms without discrimination.To distinguish and fight the pathogenic species out of the microflora,novel antimicrobials have been developed that selectively target specific bacteria and fungi.The cell wall features and antimicrobial mechanisms that these microorganisms involved in are highlighted in the present review.This is followed by reviewing the design of antimicrobials that selectively combat a specific community of microbes including Gram-positive and Gram-negative bacterial strains as well as fungi.Finally,recent advances in the antimicrobial immunomodulation strategy that enables treating microorganism infections with high specificity are reviewed.These basic tenets will enable the avid reader to design novel approaches and compounds for antibacterial and antifungal applications.

Differential Expression of Iron Deficiency Responsive Rice Genes under Low Phosphorus and Iron Toxicity Conditions and Association of OsIRO3 with Yield in Acidic Soils

With the hypothesis that iron(Fe) deficiency responsive genes may play a role in Fe toxicity conditions,we studied five such genes OsNAS1,OsNAS3,OsIRO2,OsIRO3 and OsYSL16 across six contrasting rice genotypes for expression under high Fe and low phosphorus(P) conditions,and sequence polymorphism.Genotypes Sahbhagi Dhan,Chakhao Poirieton and Shasharang were high yielders with no bronzing symptom visible under Fe toxic field conditions,and BAM350 and BAM811 were low yielders but did not show bronzing symptoms.Hydroponic screening revealed that the number of crown roots and root length can be traits for consideration for identifying Fe toxicity tolerance in rice genotypes.Fe contents in rice roots and shoots of a high-yielding genotype KMR3 showing leaf bronzing were significantly high.In response to 24 h high Fe stress,the expression levels of OsNAS3 were up-regulated in all genotypes except KMR3.In response to 48 h high Fe stress,the expression levels of OsNAS1 were3-fold higher in tolerant Shasharang,whereas in KMR3,it was significantly down-regulated.Even in response to 7 d excess Fe stress,the transcript abundances of OsIRO2 and OsNAS3 were contrasting in genotypes Shasharang and KMR3.This suggested that the reported Fe deficiency genes had a role in Fe toxicity and that in genotype KMR3 under excess Fe stress,there was disruption of metal homeostasis.Under the 48 h low P conditions,OsIRO2 and OsYSL16 were significantly up-regulated in Fe tolerant genotype Shasharang and in low P tolerant genotype Chakhao Poirieton,respectively.In silico sequence analysis across 3 024 rice genotypes revealed polymorphism for 4 genes.Sequencing across OsIRO3and OsNAS3 revealed nucleotide polymorphism between tolerant and susceptible genotypes for Fe toxicity.Non-synonymous single nucleotide polymorphisms and insertion/deletions(InDels) differing in tolerant and susceptible genotypes were identified.A marker targeting 25-bp InDel in OsIRO3,when run on a diverse panel of 43 rice genotypes and a biparental population,was associated with superior performance for yield under acidic lowland field conditions.This study highlights the potential of one of the vital genes involved in Fe homeostasis as a genic target for improving rice yield in acidic soils.

Phytochemical composition and toxicity assessment of Ammi majus L.

Objective:To assess the acute and subacute toxicity as well as the phytochemical composition of two extracts and three fractions of Ammi majus L.Methods:The aqueous extracts were prepared separately by maceration for 48 h and by infusion for 1 h,while the fractions were prepared by the Soxhlet extractor,successively employing cyclohexane,ethyl acetate,and ethanol.The acute toxicity study was carried out in accordance with the OECD N°423 guideline at a single dose(2000 mg/kg)in mice for 14 days.The subacute toxicity study was performed by a daily oral administration of 250 mg/kg 2 for 10 d and 100 mg/kg doses for 28 d.Phytochemical screening was performed using staining and precipitation reactions,while the chemical characterization of some analytes was detected by HPLC-MS/MS analysis.Results:In the acute toxicity study,no signs of toxicity such as convulsion,salivation,diarrhea,sleep and coma were observed during 30 minutes and 14 days,so the lethal dose was higher than 2000 mg/kg for each extract and fraction.The subacute toxicity results showed that at a dose of 250 mg/kg,61.10%of the animals died and the rest developed morbidity.On the other hand,at a dose of 100 mg/kg,all the animals were still alive after 28 days,with no morbidity and the biochemical parameters were normal with no abnormalities in the liver,kidneys and pancreas.Phytochemical screening indicated the presence of flavonoids,tannins,coumarins,and free quinones and the absence of alkaloids and anthocyanins.Conclusions:The extracts and fractions of Ammi majus L.are not toxic in the short and long term with a varied chemical composition.Toxicological tests on animals other than rodents and in the long term(more than 28 days)are needed to further confirm the safety of Ammi majus extracts.