Advances in liposomes loaded with photoresponse materials for cancer therapy.

Cancer treatment is presently a significant challenge in the medical domain, wherein the primary modalities of intervention include chemotherapy, radiation therapy and surgery. However, these therapeutic modalities carry side effects. Photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as promising modalities for the treatment of tumors in recent years. Phototherapy is a therapeutic approach that involves the exposure of materials to specific wavelengths of light, which can subsequently be converted into either heat or Reactive Oxygen Species (ROS) to effectively eradicate cancer cells. Due to the hydrophobicity and lack of targeting of many photoresponsive materials, the use of nano-carriers for their transportation has been extensively explored. Among these nanocarriers, liposomes have been identified as an effective drug delivery system due to their controllability and availability in the biomedical field. By binding photoresponsive materials to liposomes, it is possible to reduce the cytotoxicity of the material and regulate drug release and accumulation at the tumor site. This article provides a comprehensive review of the progress made in cancer therapy using photoresponsive materials loaded onto liposomes. Additionally, the article discusses the potential synergistic treatment through the combination of phototherapy with chemo/immuno/gene therapy using liposomes.

Integrating network pharmacology and experimental verification to investigate the pharmacological mechanisms of Buzhong Yiqi decoction in the treatment of non-small cell lung cancer.

Among all types of cancers, non-small cell lung cancer (NSCLC) exhibits the highest mortality rate with a five-year survival rate below 17% for patients. The Buzhong Yiqi decoction (BZYQD), traditional Chinese medicine (TCM) formula, has been reported to exhibit clinical efficacy in the treatment of NSCLC. Nevertheless, the underlying molecular mechanism remains elusive. This study aimed to assess the mechanistic actions exerted by BZYQD against NSCLC using network pharmacological analysis and experimental validation. The public databases were searched for active compounds in BZYQD, their potential targets, and NSCLC-related targets. The protein-protein interaction (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the core targets and signaling pathways of BZYQD against NSCLC. After screening, this study validated the results of predictions through in vitro experiments and public databases. We found 192 common targets between BZYQD and NSCLC. KEGG analysis showed that the anti-NSCLC effects of BZYQD were mediated through the PI3K-AKT signaling pathway. The results of in vitro experiment indicated that BZYQD could inhibit cell viability and proliferation of A549 and H1299 cells apart from inducing cell apoptosis. In addition, western blot results substantiated that BZYQD could treat NSCLC by inhibiting the activation of the PI3K-AKT signaling pathway. The current study investigated the pharmacological mechanism of BZYQD against NSCLC via network pharmacology and in vitro analyses. Overall, the results revealed that BZYQD could be a promising therapeutic agent for the treatment of NSCLC in the future. Still, more experimental investigations are needed to confirm the applicability of BZYQD for clinical trials.

Recent Advances on the Antimicrobial Activities of Schiff Bases and their Metal Complexes: An Updated Overview.

Schiff bases represent a valuable class of organic compounds, synthesized via condensation of primary amines with ketones or aldehydes. They are renowned for possessing innumerable applications in agricultural chemistry, organic synthesis, chemical and biological sensing, coating, polymer and resin industries, catalysis, coordination chemistry, and drug designing. Schiff bases contain imine or azomethine (-C=N-) functional groups which are important pharmacophores for the design and synthesis of lead bioactive compounds. In medicinal chemistry, Schiff bases have attracted immense attention due to their diverse biological activities. This review aims to encompass the recent developments on the antimicrobial activities of Schiff bases. The article summarizes the antibacterial, antifungal, antiviral, antimalarial, and antileishmanial activities of Schiff bases reported since 2011.

Evaluation of potential bacterial protease inhibitor properties of selected hydroxyquinoline derivatives: an in silico docking and molecular dynamics simulation approach.

Antimicrobial drug resistance (AMR) is a severe global threat to public health. The increasing emergence of drug-resistant bacteria requires the discovery of novel antibacterial agents. Quinoline derivatives have previously been reported to exhibit antimalarial, antiviral, antitumor, antiulcer, antioxidant and, most interestingly, antibacterial properties. In this study, we evaluated the binding affinity of three newly designed hydroxyquinolines derived from sulfanilamide (1), 4-amino benzoic acid (2) and sulfanilic acid (3) towards five bacterial protein targets (PDB ID: 1JIJ, 3VOB, 1ZI0, 6F86, 4CJN). The three derivatives were designed considering the amino acid residues identified at the active site of each protein involved in the binding of each co-crystallized ligand and drug-likeness properties. The ligands displayed binding energy values with the target proteins ranging from -2.17 to -8.45 kcal/mol. Compounds (1) and (3) showed the best binding scores towards 1ZI0/3VOB and 1JIJ/4CJN, respectively, which may serve as new antibiotic scaffolds. Our in silico results suggest that sulfanilamide (1) or sulfanilic acid (3) hydroxyquinoline derivatives have the potential to be developed as bacterial inhibitors, particularly MRSA inhibitors. But before that, it must go through the proper preclinical and clinical trials for further scientific validation. Further experimental studies are warranted to explore the antibacterial potential of these compounds through preclinical and clinical studies.Communicated by Ramaswamy H. Sarma.

Synthesis of novel silica encapsulated spiropyran-based thermochromic materials.

A series of novel spiropyrans were synthesized through the condensation of substituted 3,3-dimethyl-2-methyleneindoline with different nitro-substituted o-hydroxy aromatic aldehydes. Indoles were initially substituted with a variety of alkanes and esters moieties. The substituted 3,3-dimethyl-2-methyleneindoline was then reacted with nitro-substituted o-hydroxy aromatic aldehydes to yield the respective spiropyrans. The synthesized novel spiropyrans were encapsulated in silica nano-shells to protect them from the effect of moisture and pH. The thermochromic behaviour of novel spiropyrans was studied by UV-visible spectroscopy. The thermally induced isomerization of spiropyran derivatives was carried out in a water/ethanol mixture. The thermal isomerization of spiro-heterocyclic (colourless form) to merocyanine (MC) (coloured form) was a discontinuous process and was observed in a temperature range of 5-60°C via UV-visible spectrometer. The absorption process occurs reversibly regardless of the heating/cooling sequence. The spiropyran derivatives, therefore, have a potential application for colorimetric temperature indication.

Negative Pressure Wound Therapy (NPWT): Our Experience in Pakistan With Locally Made Dressing.

Introduction Worldwide numbers of patients suffering from complex wounds appear to increase annually. These patients present with acute, sub-acute and chronic wounds which can be difficult to manage. Management of these patients typically requires a multi-disciplinary approach by a plastic surgeon, orthopaedic surgeon and infectious disease control team. Despite the advent of numerous new techniques and technologies, negative pressure wound therapy (NPWT) remains a cornerstone to the management of complex wounds. We present our experience with NPWT in this study. Methods This is a retrospective study of 380 patients who were treated with NPWT in the last 10 years at a single center. We receive hundreds of infected wounds of limbs each year which are either post-traumatic or post-debridement. Frequency of dressing change, C-reactive protein levels, bacterial cultures, complication rate and cost of apparatus in each case were noted. All patients received systemic antibiotics during the treatment. Results We reviewed hospital data of 520 patients in which debridement was performed. Of the 520 patients derided, 380 patients were treated with NPWT, and included in study. Number of NPWT sessions was decided on the basis of wound status (adequate healthy granulation tissue, clinically improved circulation). A single session of NPWT dressing was applied in 84% (n = 320) patients, 8% (n = 31) patients needed two sessions of NPWT dressing, 6% (n = 24) patients had three sessions of NPWT dressing and only 1% (n = 5) patients did not respond to NPWT dressing. 78% (n = 297) patients had reduced levels of C-reactive protein levels and wound cultures were negative in 54% (n = 208) patients after application of NPWT dressing. Minor complications occurred in 0.7% (n = 3) patients due to occult osteomyelitis. In 0.5% (n = 2) patients, NPWT dressing was discontinued due to persistent leakage near a natural orifice. Sinus formation was seen in 6% (n = 23) patients who were treated with curettage and conventional dressings. The mean pain score on the verbal analogue scale was 3 out of 10. The mean cost of an NPWT dressing apparatus was 90 dollars. Conclusion We conclude from this study that NPWT dressing can be easily applied to any region of the body and it can be customized to the needs of patients from different socio-economic status.

Resection and Reconstructive Options in the Management of Dermatofibrosarcoma Protuberans of the Head and Neck.

Objective To discuss resection and various reconstructive options in patients with dermatofibrosarcoma protuberans (DFSP). Methods This study was conducted at Shifa International Hospital, Islamabad, Pakistan, from May 2018 to December 2019. All patients aged 20 years or above of either gender who were diagnosed to have DFSP over this period were included in the study. All the patients underwent wide local excision of the tumor under general anesthesia. A peroperative frozen section was conducted in all the cases to confirm complete excision. Immediate reconstruction was performed following the tumor excision. The choice of reconstruction, i.e. free, regional, or local flap was based on the size of the resultant defect. Results The mean age of the patients was 37.11 ±10.91 years. There were 12 (66.7%) males and six (33.3%) females. The mean duration of the disease was 11.22 ±2.94 months. The affected anatomical site showed that the face was involved in the majority, nine (50%) patients, followed by the scalp in four (22.2%), nape of the neck in three (16.7%), and supraclavicular region in two (11.1%) patients. In most of the cases, the free flap was observed, i.e. (n=9, 50%), followed by a regional flap in seven (38.9%), and the local flap in two (10.1%) patients. Conclusion Wide local excision of the disease, confirmed on frozen section, offers improved survival. Among DFSP of the head and neck, the face was found to be the affected anatomical site in half the cases. Also, reconstruction following tumor excision with a free flap is the most favorable option among patients with DFSP.

Anti-cancer potential of sophoridine and its derivatives: Recent progress and future perspectives.

Cancer is the second leading cause of mortality and has resulted in about 9.6 million deaths around the world in 2018. Cancer-caused deaths are expected to be 11.5 million by 2030 all over the world. Because of the fatal nature of cancer, substantial efforts are made all over the world to combat it. Phytoconstituents such as certain alkaloids, saponins, tannins, polyphenols, and terpenoids exhibit anticancer effects. Sophoridine is a tetracyclic quinolizidine alkaloid isolated from the stem and leaves of medicinal plants Sophora alopecuroides L., and Euchresta japonica Benth, and roots of Sophora alopecuroides Ait. Chinese Food and Drug Administration (CFDA) approved sophoridine as an antitumor agent in 2005. This review covers the antitumor activities of sophoridine and its derivatives. The efficacy of sophoridine analogs is expressed with respect to their half-maximal inhibitory concentration (IC50 values). Structure-activity relationship (SAR) study for most of the sophoridine derivatives has been explained. Moreover, the current market of anticancer drugs and its expected growth are discussed. Prospects provide suggestions and clues for novel sophoridine-based anticancer agents with enhanced expected efficacy and minimum toxicity.

New modification strategy of matrine as Hsp90 inhibitors based on its specific L conformation for cancer treatment.

The similarity of spatial structure between radicicol and matrine urged us to perform conformation modification of matrine, followed by L-shaped matrine derivatives, 6, 12, 21a-h and 22a-h were originally designed, synthesized and evaluated for Hsp90N inhibitors as anticancer agents. TSA (Thermal Shift Assay) results indicated that 21e, 22a-c and 22e-g exhibited strong binding force against Hsp90N with∣ΔTm∣ > 3, meanwhile, MTT assay also revealed these compounds displayed potent anticancer activity with IC50 values below 25 µM against HepG2, HeLa and MDA-MB-231 cells lines. Then, compound 22g with a high ΔTm = 10.92 was chosen as a representative to perform further mechanism study. It can induce cell apoptosis, arrest the cell cycle at the S phase and decrease the expression level of Hsp90 in Hela cell. These results originally provided targeted modification strategy for matrine derivatives to serve as Hsp90 inhibitors for cancer therapy.

Satisfaction in Patients After Rhinoplasty Using the Rhinoplasty Outcome Evaluation Questionnaire.

Introduction Rhinoplasty is a challenging procedure. The goal of the surgery is not only to restore the function and youthful appearance of the nose but also to improve quality of life. With the passage of time, the trend has been changing rapidly from more invasive to less invasive procedures. Although the technical aspects of rhinoplasty are important, patient satisfaction is the factor that dictates the success of the procedure. Materials and methods A total of 118 rhinoplasties were performed in our department between 2016 and 2018. The Rhinoplasty Outcome Evaluation (ROE) questionnaire was used to study the patients' satisfaction level. Ninety out of 118 patients took part in this study. Rhinoplasty was done using an open technique in all cases. The ROE questionnaire was filled preoperation and six months postoperation. Data analysis was done using SSPS statistic version 20 (IBM Corp., Armonk, NY, US). Results The main reasons for rhinoplasty in our patients were: aesthetic 23.3% (n=21), functional 25.5% (n=23), and a combination of both in 51% (n=46) patients. The mean ROE score of all patients preoperation was 30.5 (males: 31.3, females 29.8) and the mean score postoperation was 79.5 (males 78.2, females 80.9) at six months with no statistical differences (CI 17.11 - 12.59, P=0.762). However, both genders showed a statistically significant improvement between the preoperative and postoperative scores (mean difference = 49.3, CI 63.25 - 35.34, P<0.01), indicating an overall good satisfaction level after surgery. The satisfaction level of patients was inversely proportional to their level of understanding and knowledge of the surgical procedure. This difference was statistically significant ( CI 7.36-10.42, P<0.01). Minor corrections or modifications were done in eight patients under local anesthesia, with no significant difference in ROE scores as compared to those who had single surgery (CI 0.7 - 1.6, P=0.92). There was no statistically significant difference in the before and after surgery ROE scores among patients operated by different surgeons as well (P=0.82). Conclusion Our study shows that rhinoplasty, despite being a complex procedure, has proven benefits in terms of functional as well as aesthetic outcomes. The ROE questionnaire proves to be a valid tool for estimating patient satisfaction in our population. There is a need for further training and education of surgeons in Pakistan to improve the functional and aesthetic disabilities of nasal deformities.

Functional Outcomes of Secondary Procedures in Upper Extremity Replantation and Revascularization.

Introduction Traumatic amputation of the upper limb has significant associated morbidities and disabilities. After successful replantation surgery, the micro-surgeons' tasks are far from over. The replanted and revascularized segments have numerous functional restrictions and need various corrective secondary procedures. The aim of our study was to compare the functional results after secondary procedures by administering the Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) questionnaire to patients who had successful upper limb replantation and revascularization. Materials and methods This prospective observational study involved 40 patients who had a partial or complete amputation of the upper limb and underwent secondary procedures to correct function after successful replantation and revascularization surgery. The patients' functional outcomes after various secondary procedures were recorded using the QuickDASH questionnaire. Results The mean QuickDASH score for thumb injuries was 42.3 pre-surgery but improved to 29.5 after secondary procedures, which was statistically significant (CI 11.12-14.87, p<0.01). The mean difference in the QuickDASH scores for finger injuries was also statistically significant: 45.5 preoperation and 33.7 postoperation (CI 9.89-13.70, p<0.01). For wrist injuries, the mean QuickDASH score was 52.8 presurgery and was 46.3 postoperatively (CI 1.81-6.58, p=0.0023). The QuickDASH scores of the patients with arm and forearm injuries showed no statistically significant improvement, with a preoperation score of 58.3 declining to 55.2 (p=0.98). The overall replantation and revascularization scores were 49.725 and 41.175 pre and postoperation, respectively (CI 8.35-8.75, p<0.01). Conclusion The study finds that the level and mechanism of injury are important predictors of the functional outcomes of the replantation and revascularization of amputated upper-limb appendages. Most replanted and revascularized upper limbs have numerous functional limitations, and achieving good functional results requires one or more secondary procedures, whose type depends on various factors such as the injury type and mechanism. The QuickDASH results for functional outcomes before and after secondary procedures indicate that it is an easy-to-use, reliable, and effective measure of functional outcomes.

Correction of lower limb deformities with fixator assisted nailing.

INTRODUCTION: Deformities of the lower extremities can be congenital or acquired. Various surgical treatments have been employed for such disorders including osteotomy followed by either external fixation, internal fixation or external fixator assisted internal fixation. The aim of surgery is correction of deformity and restoration of mechanical axis and joint line. External fixator assisted internal fixation with intramedullary (IM) nail insertion is considered the gold standard, however, it is less commonly practiced as expertise required are usually not available at most centers. This study was conducted to assess the radiological and functional outcomes after fixator assisted IM nailing for correction of lower limbs deformity. METHODS: It was a retrospective study at a tertiary care hospital. All cases of lower limb deformity whose correction was done with fixator assisted IM nailing from 2010 till 2017 were analyzed. Pre Op x-rays and post op x rays were analyzed for Mechanical Axis Deviation (MAD), anatomical Lateral Distal Femoral Angle (aLDFA), mechanical Lateral Distal Femoral Angle (mLDFA) and Medial Proximal Tibial Angle (MPTA), post-operative activity and functional status of the patients. Data was analyzed using SPSS. RESULTS: Thirteen patients were included in the study. Fixator assisted IM nailing was performed on 29 long bones of these patients including 16 femur and 13 tibial deformities. Pre Op and Post Op comparison was done for MAD, aLDFA, mLDFA, MPTA. Pre op mean MAD was 38.87 ±â€¯25.58 post op mean MAD 17.54 ±â€¯12.25 mm. Only 2 of our patients developed knee stiffness for which manipulation under anesthesia was done. One of our patients developed weakness in toe extension, which recovered after 6 months. On follow up evaluation patients had normal range of motion and no functional limitation. CONCLUSION: Fixator assisted IM nailing for deformity correction is a better option, because it has advantages of both external fixator and internal fixator. Knee stiffness associated with external fixator can be prevented. It is more convenient for patient.

Promising anti-inflammatory effects of chalcones via inhibition of cyclooxygenase, prostaglandin E2, inducible NO synthase and nuclear factor κb activities.

Chalcones (1, 3-Diphenyl-2-propen-1-one) consist of a three carbon α, ß-unsaturated carbonyl system and act as precursors for the biosynthesis of flavonoids in plants. However, laboratory synthesis of various chalcones has also been reported. Both natural and synthetic chalcones are known to exhibit a variety of pharmacological activities such as anti-inflammatory, antitumor, antibacterial, antifungal, antimalarial and antituberculosis. These promising activities, ease of synthesis and simple chemical structure have awarded chalcones considerable attraction. This review focuses on the anti-inflammatory effects of chalcones, caused by their inhibitory action primarily against the activities and expressions of four key inflammatory mediators viz., cyclooxygenase, prostaglandin E2, inducible NO synthase, and nuclear factor κB. Various methodologies for the synthesis of chalcones have been discussed. The potency of recently synthesized chalcones is given in terms of their IC50 values. Structure-Activity Relationships (SARs) of a variety of chalcone derivatives have been discussed. Computational methods were applied to calculate the ideal orientation of a typical chalcone scaffold against three enzymes, namely, cyclooxygenase-1, cyclooxygenase-2 and inducible NO synthase for the formation of stable complexes. The global market of anti-inflammatory drugs and its expected growth (from 2018 to 2026) have been discussed. SAR analysis, docking studies, and future prospects all together provide useful clues for the synthesis of novel chalcones of improved anti-inflammatory activities.

Novel α, ß-Unsaturated Sophoridinic Derivatives: Design, Synthesis, Molecular Docking and Anti-Cancer Activities.

Using sophoridine 1 and chalcone 3 as the lead compounds, a series of novel α, ß-unsaturated sophoridinic derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity. Structure-activity relationship (SAR) analysis indicated that introduction of α, ß-unsaturated ketone moiety and heterocyclic group might significantly enhance anticancer activity. Among the compounds, 2f and 2m exhibited potential effects against HepG-2 and CNE-2 human cancer cell lines. Furthermore, molecular docking studies were performed to understand possible docking sites of the molecules on the target proteins and the mode of binding. This work provides a theoretical basis for structural optimizations and exploring anticancer pathways of this kind of compound.

Molecular modeling, simulation and docking study of ebola virus glycoprotein.

Ebola virus (EBOV) is a filamentous, enveloped, non-segmented, negative-strand ribonucleic acid (RNA) virus which belongs to family Filoviridae. Ebola virus includes different glycoproteins each of which plays their roles in different aspects of viral life cycle. In this study secreted glycoprotein (Q7T9E0) of Ebola virus was acquired from Uniprot. The formation of alpha helix and beta sheets of secondary structures were predicted through online servers. Higher flexibility and disordered regions of proteins were determined through RONN, GLOBPLOT and DISSEMBLE. Three dimensional (3D) structure of the protein was built through homology modeling techniques and MOE software. The validation and evaluation of the refined models were determined with two stereochemical tests i-e RAMPAGE and ERRAT servers. Further docking studies of given protein was performed with different derivatives of two antiviral drugs dronedarone and amiodarone through MOE. Docking score and binding affinity of respective derivatives demonstrate that these might be used as protein receptors.

Complex biological reconstruction after wide excision of osteogenic sarcoma in lower extremities.

Wide margin resection of extremity tumor sometimes leaves a huge soft tissue and bony defects in limb salvage surgery. Adequate management of these defects is an absolute requirement when aiming for functional limb. Multidisciplinary management in such cases is an answer when complex biologic reconstruction is desired. We aim to present cases of osteogenic sarcoma of lower extremity requiring combined surgical approach to achieve effective musculoskeletal reconstruction. Patients and Methods. From 2006 to 2010 ten patients were operated on for osteogenic sarcoma of lower extremity requiring complex musculoskeletal reconstruction. Results. Six patients had pathology around knee joint, whereas one each with mid tibia, mid femur, proximal femur, and heel bone. Locking compression plate was used in 7 patients including six with periarticular disease. Eight out of ten patients underwent biologic reconstruction using autograft; endoprosthetic reconstruction and hindquarter amputation were done in the remaining two patients. Vascularized fibula was done in five patients, sural artery flap which was primarily done in three patients, spare part fillet flap, free iliac crest flap, and Gastrocnemius flap was done in one patient each. Secondary hemorrhage, infection, nonunion, wound dehiscence, and flap failure were notable complications in four patients. The Average Musculoskeletal Tumor Society score was 89%. Conclusion. Combined surgical approach results in cosmetically acceptable and functional limb.

Predictors of length of hospital stay after total hip replacement.

PURPOSE: To identify variables affecting length of hospital stay after total hip replacement (THR) while controlling for potential confounders. METHODS: Records of 199 consecutive elective unilateral THRs were reviewed. Clinical and demographic data including age, gender, body mass index, comorbidities, surgical factors (surgical approach, type of prosthesis, use of cement, operating time), anaesthetic factors (type of anaesthesia, ASA physical status), and length of hospital stay were recorded. RESULTS: 64% of patients left hospital within 12 days, 28% within 3 weeks, and 8% after 3 weeks. The median length of hospital stay was longer in women than men (11.5 vs. 9 days, p=0.009), in patients aged >65 years than those younger (13 vs. 9 days, p<0.0001), and in those with American Society of Anesthesiologists (ASA) grades 3 and 4 than grades 1 or 2 (14 vs. 9 days, p<0.0001). A greater proportion of women than men (45% vs. 27%, p=0.007), patients aged >65 years than those younger (61% vs. 37% or 24%, p<0.0001), and those with ASA grades 3 and 4 than grades 1 and 2 (68% vs. 25%, p<0.0001) stayed 12 days or longer. In the multiple regression analysis, the predictors for prolonged hospital stay (12 days or more) were patient age >65 years (p<0.003), female gender (p<0.05), and ASA grades 3 and 4 (p<0.0001). Of the 72 patients with prolonged stay, 7% had no, 26% had one, 42% had 2, and 25% had all 3 predictors. CONCLUSION: Prolonged hospital stay after THR is largely predetermined by case mix. Our study helps to identify individuals who need longer rehabilitation and more care.

Biomechanical evaluation of plate osteosynthesis for AO type C2 fracture of the distal radius--a cadaver study.

An AO type C2 distal radius fracture was simulated in a cadaver model by creating a metaphyseal defect of 5 mm and an intra-articular defect of 2 mm. Five different methods of plate osteosynthesis were tested biomechanically in each of six fresh cadaveric hands. Biomechanical testing suggested that cement augmented plating plus screws in the distal fragment was the strongest. Dorsal and volar plating plus screws on both sides of the distal fragment had the same effect of restoring stiffness and load transmission pattern as fixation with double plating plus volar screws alone. Fixation with plating plus dorsal screws was significantly weaker than these three methods, and double buttress plating with no screws in the distal fragments was the weakest.