Emergency chest wall reconstruction in open pneumo-thorax from gunshot chest: A case report.

Chest trauma, penetrating or blunt is common in this era of motor vehicle accidents, violence and terrorism in South Asia. Islamabad is the capital of Pakistan but there is no dedicated chest surgery unit in any government sector hospitals. Gunshot chest, is therefore managed by general surgery team in our tertiary care setting i.e. Federal Government Polyclinic Hospital and Post Graduate Medical Institute, Islamabad. We report a case of gunshot chest with lung contusion and open pneumothorax with a chest wall defect of 10 x 15 cm. in March 2015, this young man presented in emergency department of Federal Government Polyclinic Hospital (FGPC), Post Graduate Medical Institute (PGMI) Islamabad in shock after self-inflicted point blank suicidal gunshot to his left anterolateral chest. After primary resuscitation, the patient was shifted to OR, and a left anterolateral thoracotomy performed. Lung contusion was repaired and chest drain placed. The challenging task of closing the huge chest wall defect was performed by rotating the left latissimus dorsi muscle flap. The patient was shifted to ICU and remained stable postoperatively.

Stability Studies and Characterization of Glutathione-Loaded Nanoemulsion.

Glutathione reduced (GSH) is the mother of all the antioxidants and has an antimelanogenic effect. It is extremely vulnerable to oxidation in the solution form which limits its use. The GSH in nano-oil droplets present a potential solution to this problem. The aim of this study was to formulate glutathione-loaded nanoemulsion and assess its stability studies over a 90-day testing period. To formulate GSH-loaded nanoemulsion pseudo-ternary phase diagram, it was built with various concentrations of water, liquid paraffin oil, and surfactant mixture (Tween 80 and Span 80). The oily phase was prepared by dissolving the GSH (450 mg) in liquid paraffin oil through stirring. High-energy homogenization was used to prepare the nanoemulsion. From preformulation stability studies of the 28-day testing period, nanoemulsion (NE-19) with oil and surfactant mixture ratio (1:1) of hydrophilic lipophilic balance (HLB) value 10 was selected. The samples of NE-19 and its respective base (B-19) were kept at four different storage conditions for a period of 90 days and evaluated for physical characteristics, droplet size and distribution analysis, zeta potential analysis, electrical conductivity, mobility, polydispersity, pH, phase separation, and flow analysis at different time intervals. Glutathione in nano-oil droplets with nonionic surfactants produced oil-in-water nanoemulsions that were thermodynamically stable over the 90-day testing period at different storage conditions. NE-19 was formulated having non-Newtonian flow and pseudo-plastic behavior. pH was found in the range of 5-6. Polydispersity was less than 0.3. The droplet size of fresh nanoemulsion was 96.05 nm, whereas the zeta potential was -37.1. Mobility and electrical conductivity were -2.726 µm cm/Vs and 0.0141 mS/cm, respectively. Glutathione-loaded nanoemulsions have excellent stability, promising the solution in nano-oil droplets and are suggested for in-vivo release studies for oxidative skin related diseases.

Central venoplasty in AV (Arteriovenous) fistula dysfunction a palliative endovascular approach.

The ultimate treatment of chronic kidney disease is renal transplant. Patients with CKD who need temporary haemodialysis have to have indwelling catheters. The catheters used are either temporary or permacath (A permacath is a piece of plastic tubing very similar to jugular catheter used for haemodialysis). The issues with these catheters are stenosis of central vein especially subclavian. Central venous stenosis leads to impairment in optimal dialysis. We report two cases of central venous stenosis in which patients presented with pain and oedema of the arm. Venogram showed totally occluded right subclavain vein and left innominate vein. Venoplasty was done which on followup showed a normalization of arm and resumption of dialysis through AV fistula. .

Stimuli-sensitive biomimetic nanoparticles for the inhibition of breast cancer recurrence and pulmonary metastasis.

Biomimetic nanoparticles represent a promising avenue for mitigating rapid clearance by the reticuloendothelial system (RES); however, current challenges include insufficient tumour targeting, suboptimal adhesion, and inadequate localized drug release within tumour regions. These shortcomings contribute to persistent contests, such as recurrence and pulmonary metastasis, even with advanced breast cancer therapies. Stimuli-sensitive drug release can furbish the membrane coated nanoparticles for their efficiency against the stated problems. To enhance the efficacy of biomimetic nanoparticles in addressing these issues, we proposed a versatile, stimuli-responsive drug delivery system by encapsulating doxorubicin (Dox) and perfluorohexane (PFH) within poly (lactic-co-glycolic acid) (PLGA) nanoparticles, subsequently coated with macrophage-derived cell membranes. Within this framework, PFH serves as the mediator for ultrasonic (US)-irradiation-triggered drug release specifically within tumour microenvironment, while the macrophage-derived cell membrane coating enhances cell adhesion, enables immune evasion, and natural tumour-homing ability. The characterization assays and in vitro evaluations yielded encouraging results, indicating enhanced targeting and release efficiencies. In vivo studies demonstrated marked inhibitory effects on both breast cancer recurrence and pulmonary metastasis. The resulting data indicate that these engineered nanoparticles have notable potential for targeted delivery and controlled release upon US irradiation, thereby offering significant therapeutic efficacy against primary breast cancer, pulmonary metastasis, and recurrent malignancies. Our findings lay the groundwork for a novel clinical approach, representing an intriguing direction for ongoing investigation by oncologists.

Albumin-coated green-synthesized zinc oxide nanoflowers inhibit skin melanoma cells growth via intra-cellular oxidative stress.

Zinc oxide (ZnO) has attracted a substantial interest in cancer research owing to their promising utility in cancer imaging and therapy. This study aimed to synthesized ZnO nanoflowers coated with albumin to actively target and the inhibit skin melanoma cells. We synthesized bovine serum albumin (BSA)-coated ZnO nanoflowers (BSA@ZnO NFs) and evaluated it's in vitro and in vivo therapeutic efficacy for skin cancer cells. BSA@ZnO NFs were prepared via single-step reduction method in the presence of plant extract (Heliotropium indicum) act as a capping agent, and further the successful fabrication was established by various physico-chemical characterizations, such as scanning electron microscopy (SEM), Fourier transform infra-red (FT-IR) spectroscopy, and x-rays diffraction (XRD) analysis. The fabricated BSA@ZnO NFs appeared flower like with multiple cone-shaped wings and average hydration size of 220.8 ± 12.6 nm. Further, BSA@ZnO NFs showed enhanced cellular uptake and cytocidal effects against skin cancer cells by inhibiting their growth via oxidative stress compared uncoated ZnO NFs. Moreover, BSA@ZnO NFs showed enhance biosafety, blood circulation time, tumor accumulation and in vivo tumor growth inhibition compared to ZnO NFs. In short, our findings suggesting BSA@ZnO NFs as a promising candidate for various types of cancer treatment along with chemotherapy.

Bio-evaluations of sericin coated hesperidin nanoparticles for gastric ulcer management.

Gastric ulcers are worrying, and their worsening conditions may result in bleeding in the internal lining of the stomach. The problem is annoying, and both patients and professionals are still not satisfied with the available treatment options. Hesperidin, a flavonoid molecule with potent anti-inflammatory and antioxidant effects, can work like witchcraft to repair gastric ulcers and preserve the stomach lining. Here, we employed a strategy that involved covering the surface of the nano-lipid carriers (NLCs) with sericin before encasing the hesperidin within (Se-He-NLC). Sericin, a biodegradable polymer increases the muco-adhesion with stomach lining and deployment of hesperidin in controlled manner. Se-He-NLCs were physico-chemically characterized for drug loading, encapsulation, particle size, morphology, drug release, chemical stability, and chemical bonding. The nanocarriers showed first order drug release in a controlled manner. Se-He-NLCs showed better in vitro permeation and ex vivo mucoadhesion, thereby by promoting the in vivo bioavailability. Se-He-NLCs also promoted the reduced glutathione (GSH) and glutathione-S-transferase (GST) levels by 2.24- and 1.61-folds, respectively in the stomach lining, and also the regulation of superoxide dismutase (SOD) and catalase (CAT) activities parallel to the control group. In addition, tissues lipid hydroperoxides (LOOH) and myeloperoxidase (MPO) activity were reduced significantly with Se-He-NLCs administration. Se-He-NLC therapy of stomach ulcers in vivo demonstrated better binding ratio and ulcer healing potential. This approach reveals huge capacity for delivering therapies to treat gastric ulcers based on the clinical significance of sericin coated hesperidin nanocarriers in gastric ulcer treatment.

Rationalized landscape on protein-based cancer nanomedicine: Recent progress and challenges.

The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.

Chitosan/poly (3-hydroxy butyric acid-co-3-hydroxy valeric acid) electrospun nanofibers with cephradine for superficial incisional skin wound infection management.

The belated and compromised incisional skin wound healing caused by the invading of methicillin-resistance staphylococcus aureus is a serious problem in clinic. Designing a new therapeutic strategy to inhibit the growth of invading bacteria at post-surgical site might be helpful in fast healing of post-surgical wounds. In this study, we developed cephradine (Ceph) encapsulated chitosan and poly (3-hydroxy butyric acid-co-3-hydroxy valeric acid, (PHBV)) hybrid nanofibers (Ceph-CHP NFs) employing an electrospinning method to revamp the Ceph bioavailability at the post-surgical wound site to prevent the growth of invading bacteria and trigger the wound healing process. The fabricated nanofibers revealed smooth and uniform surface with a diameter range of 160 ± 25 to 190 ± 55 nm, depending on Ceph concentration. Further, the electrospun hybrid nanofibers exhibited a higher entrapment efficiency (EE) and drug loading capacity (DLC) nearly 72.8 ± 5.2 % and 16.5 ± 3.2 %, respectively. Moreover, the Ceph-CHP NFs showed high swelling rate and biodegradation in presence of lysozyme in contrast to blank CHP NFs. Ceph-CHP NFs exhibited fast drug release in initial few hours followed by slow and controlled drug release drug up to 48 h with a constant rate. In-vitro antimicrobial studies indicated the heightened efficacy of Ceph-CHP NFs against MRSA clinical isolates and exhibited no visible cytotoxicity against keratinocytes, HC11 and L929 cells. Lastly, Ceph-CHP NFs showed the enhanced wound healing and bacterial clearance from post-surgical wound compared to Ceph in C57BL/6 mice skin model. Overall, our results showed that Ceph-CHP NFs might be used as a promising wound dressing material for MRSA-infected post-surgical wounds.

Eco-Friendly Sustainable Nanocarriers to Treat Oxidative Stresses and Skin Aging-Related Ailments, Valorization of a By-Product.

The peel from Citrus-sinensis L. is a medicinally significant food waste, and its extract (O-Ext) could be significant against oxidative stresses and skin aging, However, the penetration barriers, instability in formulation, undefined toxicities, and enzymatic activities make the O-Ext difficult to formulate and commercialize. The goal of this study was to evaluate O-Ext against oxidative stress, prepare O-Ext-loaded nano-lipid carriers (O-NLCs), and load them into topical O/W-emulsion (O-NLC-E) to improve O-Ext permeation and its in vivo antiaging effects. TPC, TFC, DPPH activity, and mineral/metal contents of O-Ext were determined via atomic-absorption spectroscopy. For bioactive compounds profiling, GC-MS analysis was carried out. O-NLCs were prepared and tested for physicochemical attributes, while HaCaT and fibroblast cells were used to study permeation and cytotoxicity. The kinetic characteristics of ex vivo permeation through rat skin were established, following the Higuchi model. Following written consent, safety investigations were conducted on human volunteers for three months, where optimized O-NLC-E and B-NLC-E were regularly applied on cheeks. Non-invasive procedures were used to assess the volunteer's skin erythema, TEWL, sebum level, melanin, hydration, pH, elasticity, and pore sizes after specified intervals. The results demonstrated that applying O-NLC-E formulation to the skin of volunteers directed significant antiaging benefits. The study offers nanotechnology-based sustainability approach against skin ageing.

Loratadine oral bioavailability enhancement via solid dispersion loaded oro-dispersible films: Formulation, characterization and pharmacokinetics.

Loratadine (LRD) belongs to second-generation tricyclic H1 antihistamine class, known for its non-sedating properties in allergic reactions. H1 antihistamines avoid and block the responses to allergens or histamine in nose and conjunctivae, thereby abolishing itching, congestion and sneezing. LRD is a Biopharmaceutical Class System (BCS) class II drug with dissolution or solubility limited absorption which limited the oral bioavailability and therapeutic efficacy of LRD. To improve the oral bioavailability of LRD for allergic disease (urticaria) treatment, LRD solid dispersions (LRD-SDs) were integrating into oro-dispersible films (ODFs). LRD-SDs were prepared through hot-melt extrusion method (HME) using d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS-1000), and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SP). Subsequently, LRD-SDs were incorporated in ODFs by solvent casting method. The physicochemical and mechanical properties of LRD solid dispersions-loaded oro-dispersible films (LRD-SDs-ODFs), were evaluated. The in-vitro dissolution, ex-vivo permeation, oral bioavailability, and pharmacodynamics studies were conducted to evaluate LRD-SDs-ODFs efficiency. LRD-SDs-ODFs showed superior solubility and in-vitro dissolution results compared to that of pure LRD (p < 0.05). The solubility of the LRD-SD coded as LTS-4 was 190 times higher than the pure drug in aqueous media. The average hydrodynamic particle size (PS), polydispersity index (PDI), and zeta potential (ZP) of SD particles were 76 ± 2.1 nm, 0.20 ± 0.08 and - 19.16 ± 1.4 mV, respectively. Moreover, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results confirmed the amorphousness of LRD in LRD-SDs-ODFs. The permeability flux of LRD was 44.6 ± 3.1 µg/cm2/h from DPF-5 formulation. Likewise, in vivo oral bioavailability of DPF-5 in Sprague-Dawley rats was significantly increased (p < 0.05) compared to free LRD. Further, wheal area was reduced 20 % higher than LRD in 8 h (p < 0.05). Overall, LRD-SDs-ODFs considerably enhanced LRD solubility, dissolution rate, bioavailability, and antihistaminic efficacy. Our findings show that SDs-ODFs is an effective carrier system for delivering poorly soluble LRD.

Primary percutaneous coronary intervention in a patient with dextrocardia.

The case of a 40-year-old male with dextrocardia who presented with ST Elevated Myocardial Infarction (STEMI) is reported. Coronary angiogram was performed after due manipulation and then successful primary percutaneous coronary intervention (PCI) of Left anterior descending (LAD) coronary artery was done. His 9 months follow up primary PCI in a patient with angiogram revealed patent stent in proximal LAD. There are very few published case reports of this rare congenital anomaly addressing technical details of successful primary PCI with dextrocardia.

Effectiveness of Roflumilast in Treating Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Background Chronic obstructive pulmonary disease (COPD) is a chronic airflow obstructive condition. The mainstay of treatment is to avoid exacerbation and manage the symptoms. Roflumilast is being used as a part of treatment to reduce the inflammatory process in this disease. Method This systematic review and meta-analysis were conducted following the provided guidelines. PubMed, Cochrane Library, and Cinahl were considered for searching the desired studies selected until 19 June 2021. The eligibility criteria for inclusion and exclusion were set before selecting studies. Result Five hundred eighty (580) studies were identified at the beginning. Removal of duplicates was done using Endnote software. The eligibility criteria, including the randomized controlled trial study design and others, were applied for screening the title and abstracts. Six studies were selected for the qualitative analysis. After assessing the data from these studies, it was found that roflumilast is an effective drug to treat COPD. Roflumilast plays an essential role in improving quality of life, inflammatory process, and clinical improvement. The drug's mild to moderate adverse effects were observed, but no significant severe adverse events were reported, and the drug was well tolerated. Conclusion Roflumilast is a valuable drug that can be used for its beneficial effects on COPD exacerbation. The benefits of the drug outweigh its adverse effects.

pH-responsive albumin-coated biopolymeric nanoparticles with lapatinab for targeted breast cancer therapy.

One can enhance the therapeutic index of anti-cancer drugs using albumin as a tumor homing agent for targeted cancer therapy. Herein, we sought to load lapatinib (LAPA) into small albumin-coated biopolymeric (poly-lactic co-glycolic acid (PLGA)) nanoparticles (APL NPs) by an emulsification method to improve the anti-tumor efficacy of lapatinib. The prepared APL NPs exhibited a small spherical core with an average diameter of 120.5 ± 10.2 nm with a narrow particle size distribution, high drug loading capacity (LC of 9.65 ± 1.53 %), good entrapment efficiency (EE of 75.55 ± 3.25 %), enhanced colloidal stability and a pH-responsive controlled drug release profile. Their cell-uptake and cancer cell growth inhibition were significantly higher compared to free LAPA and uncoated PLGA-LAPA (UPL) NPs, most likely because aggressive breast tumor cells over-express albumin receptors and utilize albumin as nutrient source for their growth. In addition, APL NPs possessed enhanced tumor accumulation and prolonged blood residence time compared to free LAPA and UPL NPs, allowing for potent tumor growth inhibition while exhibiting excellent biosafety. In short, the current study exploited a new and simple strategy to concurrently improve the safety and efficacy of LAPA for breast cancer treatment.

Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model.

Pentazocine (PTZ), a narcotic-antagonist analgesic, has been extensively used in the treatment of initial carcinogenic or postoperative pain. Hepatic first-pass metabolism results in low oral bioavailability and high dose wastage. Herein, 10 mg (-)-Pentazocine (HPLC-grade) was incorporated to solid lipid nanoparticles (SLNs) using a double water-oil-water (w/o/w) emulsion by solvent emulsification-evaporation technique, followed by high shear homogenization to augment its oral bioavailability, considering the lymphatic uptake. The resulting SLNs were characterized for zeta potential (ZP), particle size (PS), and polydispersity index (PDI) using a zetasizer. The entrapment efficiency (EE) and loading capacity (LC) were calculated. Chemical interactions, through the identification of active functional groups, were assessed by Fourier-transformed infrared (FTIR) spectroscopy. The nature (crystallinity) of the SLNs was determined by X-ray diffractometry (XRD). The surface morphology was depicted by transmission electron microscopy (TEM). In vitro (in Caco-2 cells) and in vivo (in male Wistar rats) investigations were carried out to evaluate the PTZ release behavior and stability, as well as the cellular permeation, cytotoxicity, systemic pharmacokinetics, antinociceptive, anti-inflammatory, and antioxidative activities of PTZ-loaded SLNs, mainly compared to free PTZ (marketed conventional dosage form). The optimized PTZ-loaded SLN2 showed significantly higher in vitro cellular permeation and negligible cytotoxicity. The in vivo bioavailability and pharmacokinetics parameters (t1/2, Cmax) of the PTZ-loaded SLNs were also significantly improved, and the nociception and inflammation, following carrageenan-induced inflammatory pain, were markedly reduced. Concordantly, PTZ-loaded SLNs showed drastic reduction in the oxidative stress (e.g., malonaldehyde (MDA)) and proinflammatory cytokines (e.g., Interleukin (IL)-1ß, -6, and TNF-α). The histological features of the paw tissue following, carrageenan-induced inflammation, were significantly improved. Taken together, the results demonstrated that PTZ-loaded SLNs can improve the bioavailability of PTZ by bypassing the hepatic metabolism via the lymphatic uptake, for controlled and sustained drug delivery.

Two Promising Anti-Cancer Compounds, 2-Hydroxycinnaldehyde and 2- Benzoyloxycinnamaldehyde: Where do we stand?

Natural bioactive compounds with anti-carcinogenic activity are gaining tremendous interest in the field of oncology. Cinnamon, an aromatic condiment commonly used in tropical regions, appeared incredibly promising as an adjuvant for cancer therapy. Indeed, its whole or active parts (e.g., bark, leaf) exhibited significant anti-carcinogenic activity, which is mainly due to two cinnamaldehyde derivatives, namely 2-hydroxycinnaldehyde (HCA) and 2- benzoyloxycinnamaldehyde (BCA). In addition to their anti-cancer activity, HCA and BCA exert immunomodulatory, anti-platelets, and anti-inflammatory activities. The highly reactive α,ßunsaturated carbonyl pharmacophore, called Michael acceptor, contributes to their therapeutic effects. The molecular mechanisms underlying their anti-tumoral and anti-metastatic effects are miscellaneous, strongly suggesting that these compounds are multi-targeting compounds. Nevertheless, unravelling the exact molecular mechanisms of HCA and BCA remains a challenging matter which is necessary for optimal controlled-drug targeting delivery, safety, and efficiency. Eventually, their poor pharmacological properties (e.g., systemic bioavailability and solubility) represent a limitation and depend both on their administration route (e.g., per os, intravenously) and the nature of the formulation (e.g., free, smart nano-). This concise review focused on the potential of HCA and BCA as adjuvants in cancer. We describe their medicinal effects as well as provide an update about their molecular mechanisms reported either in-vitro, ex-vivo, or in animal models.

Undefeatable coronary lesion.

We report a case in which a calcification in mid left anterior descending (LAD) artery was not apparent initially on angiogram and stenting was done after inappropriate predilation resulting in underexpansion of stent. High pressure inflation, buddy wire technique, scoring and cutting balloon inflation failed to achieve the full expansion of stent.

Outcome of primary percutaneous coronary intervention at public sector tertiary care hospital in Pakistan.

OBJECTIVES: To determine the outcome of Primary Precutaneous Coronary Intervention (PCI) in our setup and compare the results with the west. METHODS: This study was conducted at a tertiary care teaching Hospital (National Institute of Cardiovascular Diseases Karachi, Pakistan) during January 1st, 2008 to December 31st, 2008. A total of 113 patients were enrolled who came with STEMI and agreed to go for Primary PCI. We excluded the patients who had history of Thrombolytic therapy within 24 hours, presented with Non ST-elevation Myocardial Infarction (NSTEMI) and coronary angiogram revealed significant left Main or equivalent disease. All Patients received Aspirin, Clopidogrel and Platelet Glycoprotein IIB IIIA Inhibitor. After Primary PCI patients were planned to follow at one month, 3 months and 6 months. Primary end point was to document death, MI, CABG and rehospitalization. RESULTS: Out of 113 cases, 102 (90.3%) were male and 11 (9.7%) were female, Mean age was 51.2 +/- 11.7 years, 54 (47.8%) patients had Hypertension, 28 (24.8%) were Diabetics and 44 (38.9%) were Smokers. Immediate success was achieved in 111 (98.2%) cases. In hospital mortality was 5.3% (3.5% in cardiogenic shock, 1.7% in non-shock patients). Mean Door to Balloon time remained 98.4 minutes. Twelve patients were lost to follow up. Therefore at 6 months, out of 101 patients, 8 (7.9%) died, 5 (4.9%) underwent Coronary Artery Bypass Graft (CABG) surgery and 5 (4.9 %) had been re-hospitalized either for recurrent myocardial infarction or heart failure. CONCLUSION: Optimal results of primary percutaneous coronary intervention can be achieved for acute STEMI in a developing country at a tertiary care public sector hospital. The results are comparable and nearly similar to the west.

Orbital mucormycosis - Post SARS-CoV-2 sequelae.

Multisystem involvement has not been uncommon in SARS-CoV-2 infection. There has been reports of devastating neurological complication both during and after the infection. Here we present a rare case of sino-orbital mucormycosis, diagnosis of which was confirmed on histopathology. Our patient presented with headache, 18 days after her recovery from SARS-CoV-2 infection and was extensively worked up for the cause. Initially she was treated as a severe sinusitis but failure to response to antibiotics treatment warranted for further investigations and imaging. Our patient had to undergo right eye enucleation plus debridement under general anesthesia. She is currently on anti-fungal treatment as advised by infectious disease department.

Escape from abluminal LRP1-mediated clearance for boosted nanoparticle brain delivery and brain metastasis treatment.

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.

SARS-CoV-2 infection with pneumonia and encephalitis.

The pandemic of severe acute respiratory virus (SARS-CoV-2) is characterized by respiratory symptoms with serious consequences, mainly associated with pneumonia and extreme ARDS. There is a lack of data about specific neurological manifestations of covid-19 infections literature. Epidemiological trials in fewer than 30% of a population reported symptoms of headache and delirium (Helms et al., 2020). Covid-19's neurotropism is still debatable, uncertain and in the present case study patient with Covid-19 is identified. He suffered with extreme respiratory complications during hospitalization and eventually died.