scholarly journals The effect of spacers in dual drug-polymer conjugates toward combination therapeutic efficacy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juan Xu ◽  
Mengdi Ma ◽  
Jean Felix Mukerabigwi ◽  
Shiying Luo ◽  
Yuannian Zhang ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Therapeutic Effect ◽  
Anticancer Agents ◽  
Therapeutic Efficacy ◽  
Combined Therapy ◽  
Single Agent ◽  
Amide Bond ◽  
Therapeutic Effects ◽  
Great Effort ◽  
Polymer Carrier

AbstractRecently, a great effort has been made to perfect the therapeutic effect of solid tumor, from single-agent therapy to combined therapy and many other polymer-drug conjugations with dual or more anticancer agents due to their promising synergistic effect and higher drug level accumulation towards tumor tissues. Different polymer-drug spacers present diverse therapeutic efficacy, therefore, finding an appropriate spacer is desirable. In this study, dual drugs that are doxorubicin (DOX) and mitomycin C (MMC) were conjugated onto a polymer carrier (xyloglucan) via various peptide or amide bonds, and a series of polymers drug conjugates were synthesized with different spacers and their effect on tumor treatment efficacy was studied both in vitro and in vivo. The result shows that the synergistic effect is better when using different linker to conjugate different drugs rather than using the same spacer to conjugate different drugs on the carrier. Particularly, the finding of this works suggested that, using peptide bond for MMC and amide bond for DOX to conjugate dual drugs onto single XG carrier could improve therapeutic effect and synergy effect. Therefore, in polymer-pharmaceutical formulations, the use of different spacers to optimize the design of existing drugs to enhance therapeutic effects is a promising strategy.

scholarly journals TBHQ Regulates the Nrf2/HO-1 Pathway to Enhance Stem Cell Treatment of Diabetic Retinopathy

2021 ◽  
Author(s):  
Ze-Peng XU ◽  
Ni TIAN ◽  
Song-Tiao LI ◽  
Kun-Meng LI ◽  
Xiao-Yu WANG ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Therapeutic Effect ◽  
Biological Effects ◽  
Combined Therapy ◽  
Diabetic Rats ◽  
Inflammatory Factors ◽  
Diabetic Rat ◽  
Human Umbilical Cord ◽  
Therapeutic Effects

Abstract Objective: To investigate the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on diabetic retinopathy (DR) in diabetic rats, and to study the mechanism of hUCMSCs in treating diabetic retinopathy by tert-butylhydroquinone (tBHQ) regulation of the Nrf2/HO-1 pathway.Methods: The diabetic rat model was induced by intraperitoneal injection of streptozotocin (STZ). The experimental animals were divided into six groups: Normal, diabetes mellitus (DM), hUCMSCs, tBHQ, combined tBHQ-hUCMSCs, and all-trans-retinoid acid (ATRA)-hUCMSCs combined group. Visual function experiments and histological analyses were performed eight weeks post intravitreal injection. Biochemical and molecular analyses were used to assess the hUCMSCs composition and its biological effects.Results: Improvements in systemic oxidative stress and inflammation were found in the tBHQ group. Although hUCMSCs had no significant effect on oxidative stress, retinal structure was improved, visual defects reduced and expression of local retinal inflammatory factors were inhibited following its application. The effect of combined therapy was better than that of single therapy. Inhibition of the Nrf2/HO-1 pathway can promote the expression of systemic inflammatory factors and inhibit the therapeutic effect of hUCMSCs in the retina.Conclusions: Intravitreal administration of hUCMSCs triggers an effective cytoprotective microenvironment in the retina of diabetic mice. Alone, however, it may not significantly improve the systemic inflammatory response of diabetes. In combination with tBHQ it may promote Nrf2expression, systemic antioxidant stress and therapeutic effects of hUCMSCs.

Therapeutic efficacy of physical combined therapy in the treatment of venous crural ulcers

2021 ◽  
pp. 026835552098245
Author(s):  
Jarosław Pasek ◽  
Sebastian Szajkowski ◽  
Grzegorz Cieślar
Keyword(s):  
Physical Therapy ◽  
Therapeutic Efficacy ◽  
Combined Therapy ◽  
Low Frequency ◽  
Medical Problem ◽  
Variable Magnetic Field ◽  
Therapeutic Effects ◽  
Initial Size ◽  
Multifunctional Device ◽  
Long Term Treatment

Objectives Venous crural ulcer is a serious medical problem indeed, which is connected with patients’ suffering and long term treatment generating high cost. The prognosis is unfavourable in many cases, as complete treatment of ulceration, when it is profound or really extensive is difficult to achieve, and sometimes impossible altogether. The aim of the study was to evaluate the therapeutic efficacy of treatment of venous crural ulcers with the use of multifunctional device LASEROBARIA–S, designed for combined physical therapy procedures. Method 147 succeeding patients (67 women and 80 men) diagnosed with venous crural ulcer participated in the study, with age varied between 41 and 79 years (average age – 70.2 years). The patients underwent a 60 day cycle of combined physical therapy, with the use of multifunctional device LASEROBARIA–S, during which therapy the lower extremity of the patient was placed in the therapeutic chamber and simultaneously subjected to the action of: local oxygen hyperbaria, low-frequency variable magnetic field and low energy light radiation emitted by semiconductor LED diodes. Prior to the therapeutic cycle and after its completion, planimetric measurements of the area of ulcer and the assessment of pain intensity with use of VAS scale were performed, in relation to selected factors potentially affecting therapeutic effects of applied therapy, as: sex and age of patients, as well as initial size of the ulcer and duration of the ulcer presence. Results After the completion of therapeutic cycle, statistically significant reduction of the area of treated ulcer was found, by 5.4 cm2 on the average (16.3 cm2 vs 10.5 cm2) (p < 0.05). Moreover, as a result of the combined therapy procedures performed, the statistically significant lowering of the intensity of pain sensation experienced by patients, assessed by means of VAS scale, was obtained (2.55 points vs 0.48 points) (p < 0.05). The obtained improvement was not dependent statistically significantly on any of analysed selected factors potentially affecting regenerative and analgesic effect of applied therapy. Conclusions The application of combined physical therapy with the use of LASEROBARIA–S device results in significant reduction of the area of the venous crural ulcer surface, as well as reduction of the intensity of accompanying pain complaints and this therapeutic effect was not dependent on sex and age of patients, as well as initial size of the ulcer and duration of the ulcer presence.

Therapeutic Perspectives of Food Bioactive Peptides: A Mini Review

2019 ◽  
Vol 26 (9) ◽  
pp. 664-675
Author(s):  
Sulochana Priya
Keyword(s):  
Bioactive Peptides ◽  
Marine Organism ◽  
Biological Effects ◽  
Amide Bond ◽  
Therapeutic Effects ◽  
Specific Sequence ◽  
The Past ◽  
Cancer Immunity ◽  
Microbial Infections ◽  
Diverse Origin

Bioactive peptides are short chain of amino acids (usually 2-20) that are linked by amide bond in a specific sequence which have some biological effects in animals or humans. These can be of diverse origin like plant, animal, fish, microbe, marine organism or even synthetic. They are successfully used in the management of many diseases. In recent years increased attention has been raised for its effects and mechanism of action in various disease conditions like cancer, immunity, cardiovascular disease, hypertension, inflammation, diabetes, microbial infections etc. Bioactive peptides are more bioavailable and less allergenic when compared to total proteins. Food derived bioactive peptides have health benefits and its demand has increased tremendously over the past decade. This review gives a view on last two years research on potential bioactive peptides derived from food which have significant therapeutic effects.

Synthesis and Antibacterial / Anticancer Activities of Compounds Containing Pyrazole Ring Linked to Piperazines

2020 ◽  
Vol 16 (4) ◽  
pp. 419-431
Author(s):  
Kishore K. Valluri ◽  
Tejeswara R. Allaka ◽  
IV Kasi Viswanath ◽  
Nagaraju PVVS
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Pyrazole Ring ◽  
Therapeutic Effects ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
Parent Molecule ◽  
Wide Range

Background: Many pyrazole piperazine derivatives are known to exhibit a wide range, thus being attractive for the drug design and synthesis of interesting class of widely studied heterocyclic compounds. It is therefore necessary to devote continuing effort for the identification and development of New Chemical Entities (NCEs) as potential antibacterial and anticancer agents to address serious health problems. Methods: A series of new compounds containing pyrazole ring linked to a piperazine hydrochloride moiety were synthesized and screened for their antibacterial activity, cytotoxicity of novel scaffolds are described by variation in therapeutic effects of parent molecule. The structure variants were characterized by using a blend of spectroscopic 1H NMR, 13C NMR, IR, Mass and chromatographic techniques. Results: When tested for in vitro antibacterial and anticancer activities, several of these compounds showed good activities. The target compounds 9b, 9a and 9e exhibited a high degree of anticancer activity against human colon cancer cell line Caco-2 and human breast cancer cell line MDAMB231. Further, 9a, 9b, 9d, and 9h showed better activity towards four medically relevant organisms; Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Klebsiella Species compared to CPF. In the present investigation, cheminfomatics tools Molinspiration, 2003 and MolSoft, 2007 for the prediction of insilico molecular properties and drug likeness for the target compounds 9a-h was evaluated and positive results were observed. Conclusion: Our study revealed that the molecular framework presented here could be a useful template for the identification of novel small molecules as promising antibacterial/ anticancer agents.

Cucurbitacins as Anticancer Agents: A Patent Review

2019 ◽  
Vol 14 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Hidayat Hussain ◽  
Ivan R. Green ◽  
Muhammad Saleem ◽  
Khanzadi F. Khattak ◽  
Muhammad Irshad ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Therapeutic Effects ◽  
Cytotoxic Effects ◽  
Natural Sources ◽  
Oh Groups ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

Background: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its cytotoxic effects. Objective: his review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and Structure-Activity Relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products. Methods: The date about the published patents was downloaded via online open access patent databases. Results: Cucurbitacins display significant cytotoxic properties, in particular cucurbitacins B and D which possess very potent effects towards a number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C(2)-OH and C(25)- OH groups. Most importantly, an acyl ester of the C(25)-OH and, iso-propyl, n-propyl and ethyl ether groups of the C(2)-OH demonstrated the most increased cytotoxic activity. Conclusion: The significant cytotoxic effects of natural and semi-synthetic cucurbitacins make them attractive as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterodimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.

scholarly journals Immunocytes as a Biocarrier to Delivery Therapeutic and Imaging Contrast Agents to Tumors

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jinhyang Choi ◽  
Ha-Na Woo ◽  
Eun Jin Ju ◽  
Joohee Jung ◽  
Hye-Kyung Chung ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Ionizing Radiation ◽  
Mouse Model ◽  
Cancer Treatment ◽  
Anticancer Agents ◽  
Anticancer Agent ◽  
Human Cancer ◽  
Genetic Alterations ◽  
Therapeutic Effects ◽  
Ionizing Radiation Exposure

Radiotherapy for cancer treatment has been used for primary or adjuvant treatment in many types of cancer, and approximately half of all cancer patients are undergoing radiation. However, ionizing radiation exposure induces genetic alterations in cancer cells and results in recruitment of monocytes/macrophages by triggering signals released from these cells. Using this characteristic of monocytes/macrophages, we have attempted to develop a biocarrier loading radiosensitizing anticancer agents that can lead to enhance the therapeutic effect of radiation in cancer treatment. The aim of this study is to demonstrate the proof of this concept. THP-1 labeled with Qdot 800 or iron oxide (IO) effectively migrated into tumors of subcutaneous mouse model and increased recruitment after ionizing radiation. Functionalized liposomes carrying a radiosensitizing anticancer agent, doxorubicin, are successfully loaded in THP-1 (THP-1-LP-Dox) with reduced cytotoxicity, and THP-1-LP-Dox also was observed in tumors after intravenous administration. Here, we report that monocytes/macrophages as a biocarrier can be used as a selective tool for amplification of the therapeutic effects on radiotherapy for human cancer treatment.

Cisplatin and doxorubicin dual-loaded mesoporous silica nanoparticles for controlled drug delivery

RSC Advances ◽  
2016 ◽  
Vol 6 (96) ◽  
pp. 94160-94169 ◽  
Author(s):  
Hanwen Li ◽  
Huijuan Yu ◽  
Caiying Zhu ◽  
Jianhua Hu ◽  
Ming Du ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Synergistic Effect ◽  
Silica Nanoparticles ◽  
Therapeutic Efficacy ◽  
Mesoporous Silica Nanoparticles ◽  
Controlled Drug Delivery

Multicomponent therapeutic platforms have been proposed to minimize dosage of each drug and reduce toxicity, leading to achieving a synergistic effect and maximizing therapeutic efficacy.

scholarly journals Inhibitory and complementary therapeutic effect of sweet lime (Citrus limetta) against RNA-viruses

2021 ◽  
Vol 7 (1) ◽  
pp. 37-44
Author(s):  
Sulagna Ray Pal ◽  
Swapan Banerjee
Keyword(s):  
Therapeutic Effect ◽  
Rna Viruses ◽  
Current Knowledge ◽  
Western World ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
Nutrient Contents ◽  
Therapeutic Benefits ◽  
Sweet Lime ◽  
Antiviral Activities

Sweet lime (), known as 'Mousambi' or 'Mosambi' in India, is one of the best citrus fruits regarding its nutrient contents. Its bioactive compounds (BAC) are exclusively used for multiple clinical applications considering many therapeutic benefits not only in Asian countries but also in the western world. The fruit pulp and juice are the best sources of ascorbic acid, B-vitamins, amino acids, and other secondary metabolites. Specifically, polyphenols such as flavanones, hesperetin, naringenin, and chlorogenic acid are highly rich in the fruit. The nutrients in sweet lime altogether provide significant anti-inflammatory, antioxidant, anti-cancer, and neuroprotective effects. The purpose of this study is to review and analyze the inhibitory and complementary therapeutic effects of sweet lime's pulp and juices to inhibit the virulence caused by RNA viruses, mainly SARS-CoV-2. This review study was designed based on extensive online searches of relevant open-access literature available in the best quality and reliable databases by using specific keywords and boolean operators. After a rigorous review, we found that flavanones in the fruit can alter or inhibit the polyproteins (pp1a and pp1b) responsible for viral replication. Therefore, sweet lime has potentialities to provide an inhibitory and a complementary therapeutic effect against RNA viruses, mainly SARS-CoV-2. About the antiviral activities, more clinical trials are needed to prove its efficacy; however, reviewing current knowledge, is one of the potent antioxidant, inflammatory fruits available and affordable almost worldwide.

scholarly journals Preconditioning Enhances the Therapeutic Effects of Mesenchymal Stem Cells on Colitis Through PGE2-Mediated T-Cell Modulation

2018 ◽  
Vol 27 (9) ◽  
pp. 1352-1367 ◽  
Author(s):  
Fu Yuan Yang ◽  
Rui Chen ◽  
Xiaohu Zhang ◽  
Biao Huang ◽  
Lai Ling Tsang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Therapeutic Effect ◽  
T Cell Activation ◽  
Activity Index ◽  
Intraperitoneal Administration ◽  
The Body ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Anti Inflammatory

Mesenchymal stem cell (MSC)-based cell therapy has been demonstrated as a promising strategy in the treatment of inflammatory bowel disease (IBD), which is considered an immune disease. While the exact mechanisms underlying the therapeutic effect of MSCs are still unclear, MSCs display anti-inflammatory and immunomodulatory effects by interacting with various immunoregulatory cells. Our previous studies have shown that MSCs can be preconditioned and deconditioned with enhanced cell survival, differentiation and migration. In this study, we evaluated the effect of preconditioning on the immunoregulatory function of human umbilical cord-derived MSCs (hUCMSCs) and their therapeutic effect on treating IBD. Our results show that intraperitoneal administration of deconditioned hUCMSCs (De-hUCMSCs) reduces the disease activity index (DAI), histological colitis score and destruction of the epithelial barrier, and increases the body weight recovery more intensively than that of un-manipulated hUCMSCs. In addition, De-hUCMSCs but not hUCMSCs elicit anti-apoptotic effects via induction of the ERK pathway during the early stage of IBD development. In vitro co-culture studies indicate that De-hUCMSCs suppress T-cell proliferation and activation more markedly than hUCMSCs. Moreover, De-hUCMSCs block the induction of inflammatory cytokines such as tumor necrosis factor (TNF)α and interleukin (IL)-2, while promoting the secretion of the anti-inflammatory cytokine IL-10 in T-cells. Mechanically, we find that prostaglandin E2 (PGE2) secretion is significantly increased in De-hUCMSCs, the suppression of which dramatically abrogates the inhibitory effect of De-hUCMSCs on T-cell activation, implying that the crosstalk between De-hUCMSCs and T-cells is mediated by PGE2. Together, we have demonstrated that preconditioning enhances the immunosuppressive and therapeutic effects of hUCMSCs on treating IBD via increased secretion of PGE2.

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