Development and Application of Procedures for the Management of Skin Toxicity Related to Immune Checkpoint Inhibitors in Patients with Lung Cancer

Objective: To establish the procedures for the management of skin toxicity related to immune checkpoint inhibitors in patients with lung cancer and explore the effect of application. Methods: A total of 24 evidence-based evidences were collected from 7 aspects, including risk factors, baseline screening, ICIs monitoring, daily skin care, multidisciplinary management, symptom management and health education. A total of 157 lung cancer patients and 94 nurses from 8 wards of the Oncology department of our hospital from November 2022 to May 2023 were selected by convenience sampling. A total of 77 patients and 46 nurses from ward 1 - 4 were divided into the baseline group. There were 80 patients and 48 nurses in Ward 5 - 8 as the evidence-based practice group. In the baseline group, patients were treated with routine methods such as assessing skin symptoms, taking medication according to symptoms, guiding to keep skin clean and moist, eating a light diet, and avoiding scratching. The evidence-based practice group adopts an evidence-based continuous improvement model for nursing. The differences in the severity of symptoms of skin toxicity in the second cycle of medication and the knowledge and practice of self-care of skin toxicity were compared between the two groups before and after the use of the syndrome, as well as the differences in the implementation rate of review indicators, evidence-based ability and knowledge and practice of skin toxicity care before and after the use of the syndrome. Results: The incidence and severity of cutaneous toxicity were significantly lower after treatment than before treatment (P P < 0.05). Conclusion: The implementation of immune checkpoint inhibitor-related skin toxicity management procedures can effectively reduce the incidence and severity of skin toxicity symptoms, optimize the clinical pathway, and improve the quality of care.

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.

Screening of Myocardial Cardiotoxicity Induced by Anticancer Chemotherapy and the Importance of Global Longitudinal Strain

Introduction: The improvement of survival in patients with cancer and the expansion of therapeutic options have led to the emergence of a new profile of cardiotoxicity, specifically associated with antimitotic agents. Our study aimed to assess the incidence of chemotherapy-induced myocardial toxicity in patients with cancer. Patients and Methods: We conducted a looking-forward longitudinal cohort study including all patients admitted to the Cardiology departments of Aristide le Dantec Hospital and Dalal Jamm National Hospital Centre for apre-chemotherapy check-up. The included patients did not undergo any pre-existing cardiopathy. Results: Over a period of two years ranging from January 2019 to December 2021, a total of 37 patients were included in the study. Notably, there was a female predominance (92%) with an average age of 49.7 years ± 13.69. Breast cancer accounted for 70% of the neoplasms. Laboratory findings revealed moderate anemia in 19 patients (51%). At inclusion, the left ventricle (LV) was of normal size (LV diastole at 44.46 ± 4.97 mm). The systolic function of the left ventricle was normal in all patients, with an average ejection fraction (EF) of 63.1% ± 5.80 and a mean global longitudinal strain (GLS) of −20.4% ± 2.58. The most commonly used agents were anthracyclines. During follow-up, 3 patients (8.1%) developed clinical symptoms of left heart failure, and LV dysfunction on echocardiography was observed in 5 (13.5%) patients, with a significant decrease in EF Conclusion: The incidence of cardiac toxicity is not negligible, hence the importance of early screening. Strain imaging is an essential tool that should be performed as part of the assessment before chemotherapy and re-evaluated during treatment.

Investigation of the Cytotoxicity of CAR-NK-92 Cells Targeting CEA Against Gastric Cancer Cells

Objective:To construct CAR-NK-92 cells targeting carcinoembryonic antigen(CEA)and study their killing effect on gastric cancer cells.Methods:CAR-NK-92 cells targeting CEA were constructed.After co-culturing CAR-NK-92 cells with MKN-45 gastric cancer cells,the killing effect of CAR-NK-92 cells was detected by a lactate dehydrogenase release assay.The secretion levels of gamma interferon and granulocyte-macrophage colony-stimulating factor were measured using an ELISA assay.Results:The lactate dehydrogenase release assay showed that CAR-NK-92 cells had a significant killing effect on MKN-45 cells compared to CON-NK-92 cells,and the difference was statistically significant(P<0.001).ELISA results indicated that the levels of gamma interferon and granulocyte-macrophage colony-stimulating factor secreted by CAR-NK-92 cells and MKN-45 target cells were significantly increased after co-culture(P<0.001).Conclusion:CAR-NK-92 cells targeting CEA exhibit a significant killing effect on CEA-positive gastric cancer cells.

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.

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.

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.

Eco-toxicity and health risk assessment of polycyclic aromatic hydrocarbons in surface sediments of Burullus Lake in Egypt

Polycyclic aromatic hydrocarbons(PAHs)are ubiquitous environmental contaminants of growing concern due to their potential ecological and human health risks.This study presents a comprehensive assessment of PAHs contamination in the surface sediments of Burullus Lake,a vital and second largest delta lake in Egypt.The aim was to evaluate the eco-toxicity and potential health risks associated with the presence of these compounds.Surface seven sediment samples were collected from various drains in the southern part of Burullus Lake.Soxhlet extraction method was employed to extract PAHs(16PAHs)from the sediment sample.Analytically,target compounds were located using HPLC.The results showed that samples contained PAHs levels ranging from 0.038×10^(-6)to 0.459×10^(-6),which is considered heavily polluted by the European standard for PAHs pollution.Additionally,there was no apparent source of PAHs in the ElKhashah drain or the Brinbal Canal,as HPLC found none of the compounds.The most prevalent compound in sediment samples along the study area was fluoranthene.The diagnostic indices in the present study indicated that the hydrocarbons in the region originated from pyrolytic and man-made sources along the drains of Burullus Lake.The principal component analysis(PCA)and diagnostic ratios revealed that coal combustion and pyrolytic sources were responsible for the PAHs contamination in the surface sediments.The non-carcinogenic risk(HI),which is the product of the HQs for the adult and child populations,respectively,was calculated.HI values under 1,therefore,demonstrated that they had no carcinogenic effects on human health.TEQs and MEQs in the sediments of Burullus Lake do not have a cancer-causing impact on people.For the safety of nearby wildlife,aquatic life,and people,all activities that raise petroleum hydrocarbon levels in Burullus Lake must be adequately regulated and controlled.According to the ecological risk assessment,there is little chance that PAHs will be found in the sediments of Burullus Lake.This study underscores the urgent need for effective pollution control measures and regular monitoring of PAHs levels in Burullus Lake sediments to protect the aquatic ecosystem and public health.It also highlights the importance of considering eco-toxicity and human health risks in integrated risk assessments of PAHs-contaminated environments.

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.

Radiation-Associated Cardiotoxicity during Breast Cancer Treatment with Ionizing Radiation

Introduction: Breast cancer is the most common cancer in women. The treatment of breast carcinoma has advanced in the last decade and nowadays there are treatment protocols for all stages of the disease. Depending on the histopathology and stage breast cancer is treated with surgery, chemotherapy and radiotherapy. Regarding radiation, the field of irradiation includes the chest wall in patients with mastectomy, or the breast glandular tissue in patients with conserving surgical approaches. It is often treated with radiation therapy with two opposing tangential fields, and when indicated supraclavicular lymph nodes have to be irradiated. In this case an additional anterior field is applied. The tangential as well as the other radiation beams have a potential damaging effect on the healthy surrounding tissues, particularly over the heart in the left breast irradiation and in the lungs as well. Material and Methods: The study included 25 patients with left breast carcinoma, all post surgery, treated with radiation therapy, with the Elekta accelerator at our department. For academic purpose the treatment plans were generated following two methods. The first one with two tangential opposite beams plus a supraclavicular beam. In this method the angles of the tangential internal and external create an angle that is equal to 180&#730;{310&#730;& 130&#730;};no further changes were made to the beam geometry. Even though this is not the best option from the dose distribution point of view, it is still the most applied method, probably because of the semplicity of it. For each patient, a second plan was generated using two opposite tangential beams plus the supraclavicular beam. The angles of the internal and external beam were changed from 1&#730;to 3&#730;, depending on the surface of the body, so that the resulting angle was 180&#730;± 3&#730;{310&#730;± 3&#730;& 130&#730;± 3&#730;} with the aim to adapt the beam geometry as much as possible to the shape of the thoracic wall and to spare the OAR-s. Results and Discussion: The data show that the dose in the organs at risk, in terms of dose percentage, is lower when the angles of the beams are changed with 1&#730;- 3&#730;, compared to the classic method where the internal and external angles equal 180&#730;. This dose is not only non-negligible but significant;for every angle change from 1&#730;to 3&#730;, there is a significant reduction in the integral dose in the radiated volume, expressed in percentage, up to 5%. Conclusion: In most centers, the radiation treatment of breast is realized with two tangential opposite beams, which usually are mirror beams, or in other words, the internal and external beam angles create an angle of 180&#730;{α + β = 180&#730;}. This is a simple method, which provides a good dose distribution, but leaves a relatively high dose in the organs at risk. This study shows the difference in the dose percentage in the heart and lung when the beam angles are changed adapting to the anatomy of the patient. Reducing these doses allows for better overall treatment and less longtime toxicity, particularly for the heart tissues.

Long Term Follow-Up of Cardiotoxicity in Breast Cancer Treatment: A Case Report

Background: Cardiac toxicity is currently defined as a symptomatic decrease in Left Ventricular Ejection Fraction (LVEF) of more than 5% or an asymptomatic decrease of at least 10% to a value of under 50% in repeated evaluations on conventional transthoracic echocardiogram (TTE), as well as a Global Longitudinal Strain (GLS) value Aims: To highlight using GLS rather than modified Simpson 2D-LVEF for the evaluation of long-term cardiotoxicity. Case Presentation: The case concerns a 73-year-old female patient with a history of breast cancer chemotherapy and anthracyclines-based therapy who presented symptoms of late cardiac toxicity related to the chemotherapeutic treatment. In the following years, the patient remained asymptomatic with a 2D-LVEF of 48%, dilation of the left atrium was found, and the reservoir phase strain was severely decreased. Conclusion: The preferred method for evaluating cardiovascular complications associated with chemotherapy is the TTE, which is performed prior to the start of treatment, during therapy, and in the follow-up. Myocardial deformation as a predictor of cardiotoxicity allows the identification of subclinical heart failure.

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.

Recent advances in breast cancer radiotherapy:Evolution or revolution,or how to decrease cardiac toxicity?

Radiation therapy has a major role in the management of breast cancers.However,there is no consensus on how to irradiate and on volume definitions,and there are strong differences in strategies according to different centers and physicians.New treatment protocols and techniques have been used with the principal purpose of decreasing lung and heart toxicity and adapting radiation treatment to patients' anatomy.There is evidence that indicates internal mammary chain radiotherapy should be used carefully and that high quality techniques should be used for decreasing the dose delivered to the heart.This review of the literature presents the state of the art on breast cancer radiotherapy,with special focus on the indications,techniques,and potential toxicity.

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.

Narrow line between benefit and harm: Additivity of hyperthermia to cisplatin cytotoxicity in different gastrointestinal cancer cells

AIM To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODS AGS(gastric cancer cell line), Caco-2(colon cancer cell line) and T3M4(pancreatic cancer cell line) were treated by cisplatin and different temperature setting(37 ℃ to 45 ℃) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7 ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin.RESULTS AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 ℃ to 41 ℃ in neither cancer cell line. However, a temperature of 43 ℃ enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3 M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3 M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 ℃ by 30%, 20%, and 18% in AGS, Caco-2, and T3 M4 cells, respectively.CONCLUSION In addition to cisplatin, hyperthermia up to 43 ℃ does not affect the viability of cancer cells in a synergistic manner.