Oxidative Stress- and Autophagy-Inducing Effects of PSI-LHCI from Botryococcus braunii in Breast Cancer Cells.

Botryococcus braunii (B. braunii) is a green microalga primarily found in freshwater, reservoirs, and ponds. Photosynthetic pigments from algae have shown many bioactive molecules with therapeutic potential. Herein, we report the purification, characterization, and anticancer properties of photosystem I light-harvesting complex I (PSI-LHCI) from the green microalga B. braunii UTEX2441. The pigment-protein complex was purified by sucrose density gradient and characterized by its distinctive peaks using absorption, low-temperature (77 K) fluorescence, and circular dichroism (CD) spectroscopic analyses. Protein complexes were resolved by blue native-PAGE and two-dimensional SDS-PAGE. Triple-negative breast cancer MDA-MB-231 cells were incubated with PSI-LHCI for all of our experiments. Cell viability was assessed, revealing a significant reduction in a time- and concentration-dependent manner. We confirmed the internalization of PSI-LHCI within the cytoplasm and nucleus after 12 h of incubation. Cell death mechanism by oxidative stress was confirmed by the production of reactive oxygen species (ROS) and specifically superoxide. Furthermore, we monitored autophagic flux, apoptotic and necrotic features after treatment with PSI-LHCI. Treated MDA-MB-231 cells showed positive autophagy signals in the cytoplasm and nucleus, and necrotic morphology by the permeabilization of the cell membrane. Our findings demonstrated for the first time the cytotoxic properties of B. braunii PSI-LHCI by the induction of ROS and autophagy in breast cancer cells.

Multi-layered stimuli responsive DNA micelles for the stepwise controlled release of small molecules.

Controllable release of multiple distinct cargoes from a nanomaterial is crucial to a variety of therapeutic and catalytic applications. In this study, we describe a DNA functionalized multi-layered surface crosslinked micelle (mlSCM) consisting of individually degradable layers. The DNA modified mlSCM has the ability to encapsulate separate small molecule cargo in distinct compartments within the nanocapsule, separated by chemical crosslinkers. Through a multistep self-assembly process, we show physical separation of internalized cargo as evidenced by electron microscopy, along with observation of chemical control over release, and chemical reaction conditions, as seen by fluorescence spectroscopy and a high-performance liquid chromatography mass spectrometry assay. Additionally, we evaluated the ability of these DNA crosslinked micelles to co-release two separate cargoes into the same cellular environment through an in vitro confocal microscopy assay. We show individualized targeting of two distinct but related dyes for the detection of ATP and mitochondria. The colocalization of these dyes indicates that unique locations and signals related to cellular respiration can be identified using a single mlSCM. Through these studies we ultimately show that the mlSCM has a tailorable design with the potential to be applied to numerous applications, ranging from sensing to drug delivery.

Outcomes of laser surgery for stage I twin-twin transfusion syndrome.

OBJECTIVE: A recent randomized controlled trial (RCT) demonstrated no difference in 6 month survival in expectantly managed stage I twin-twin transfusion syndrome (TTTS) patients and those undergoing immediate laser surgery. We aimed to describe outcomes following immediate laser surgery at a single fetal surgery center. METHODS: A retrospective study of monochorionic diamniotic twins diagnosed with stage I TTTS who underwent laser surgery between 16 and 26 gestational weeks from 2006 to 2019. The primary outcome was 6 month survivorship. Intact survival was also assessed. Secondarily, outcomes were compared to the RCT expectant management group. RESULTS: Of 126 consecutive stage I TTTS patients, 114 (90.5%) met inclusion criteria. Median (range) gestational age at delivery was 34.1 (20.6-39.4) weeks. At 6 months, the proportion of patients with at-least-one survivor in the single-center-laser cohort was 97.4%, with 88.6% dual survivorship. Neurological morbidity outcomes were available in 110 pregnancies (220 fetuses). Severe neurological morbidity occurred in 2.7% (6/220), and 6 month survival without severe neurological morbidity was 90.0%. Outcomes compared favorably with the RCT expectant management group. CONCLUSIONS: Given favorable survival and neurological outcomes, laser surgery is a reasonable treatment option for stage I TTTS at experienced fetal surgery centers. Further study is warranted to optimize treatment strategies.

Improving On-Time First Case Starts: An Integrative Review and Quality Improvement Project Plan.

PURPOSE: Surgeon late arrival is the major cause of delays in first case starts. The estimated cost of these delays can reach $800,000 a year. The purpose of this integrative review and proposed quality improvement (QI) project plan was to increase the first case on-time starts through surgeon behavior modification. DESIGN: An integrative literature review and creation of a QI project plan. METHODS: The literature review included an independent electronic literature search between the years of 2011 and 2020 through CINAHL PLUS, PubMed, and Medline OVID databases. The search was limited to scholarly peer-reviewed journal articles in the English language, and search terms included: "operating rooms," "delay first cases start," "first case tardiness," and "operating room efficiency." The QI project plan was a three-phase process based on surgeon behavioral modification using educational material, visual reminders, and individualized e-mail notifications of habitually late surgeons. FINDINGS: A synthesis of articles reported proper site marking and surgical consent 15 to 30 minutes before surgery increased first case on-time starts from 55.90% to 66.60% and a mean delay decrease of 9.67 minutes to 7.17 minutes. Visual cues significantly enhanced memory, 64% versus 50%, and e-mail reminders increased compliance, 77% to 86.1%. CONCLUSION: As the need for hospital revenue dependency grows, so will the need for more efficient operating rooms. The evidence shows a positive correlation between early arrival by surgeons to the preoperative area and increased on-time first case starts.

Cardiovascular Collapse During Transurethral Resection of Bladder Tumor: A Case Report.

Despite innovative modalities, transurethral resection (TUR) procedures are the primary surgical intervention for bladder tumor and enlarged prostate. TUR syndrome, a major complication of TUR procedures, leads to derangement in electrolytes, hemodynamic compromise, and possible cardiac arrest. This case report describes cardiovascular collapse in a 60-year-old male during TUR of a bladder tumor under general anesthesia. The patient developed hypoxia, which progressed to cardiovascular collapse. Electrolyte analysis revealed acute hyponatremia. The patient was resuscitated successfully, transferred to intensive care unit, and discharged from the hospital without any complications. This case report of a cardiovascular collapse during transurethral resection of bladder tumor offers insight of the risks in urologic procedures and highlights the importance of clear communication as well as early recognition and successful management of complications.

Programmable Peptide-Cross-Linked Nucleic Acid Nanocapsules as a Modular Platform for Enzyme Specific Cargo Release.

Herein we describe a modular assembly strategy for photo-cross-linking peptides into nucleic acid functionalized nanocapsules. The peptides embedded within the nanocapsules form discrete nanoscale populations capable of gating the release of molecular and nanoscale cargo using enzyme-substrate recognition as a triggered release mechanism. Using photocatalyzed thiol-yne chemistry, different peptide cross-linkers were effectively incorporated into the nanocapsules and screened against different proteases to test for degradation specificity both in vitro and in cell culture. By using a combination of fluorescence assays, confocal and TEM microscopy, the particles were shown to be highly specific for their enzyme targets, even between enzymes of similar protease classes. The rapid and modular nature of the assembly strategy has the potential to be applied to both intracellular and extracellular biosensing and drug delivery applications.

Nativity and neighborhood characteristics and cervical cancer stage at diagnosis and survival outcomes among Hispanic women in California.

OBJECTIVES: We examined stage of diagnosis and survival after cervical cancer among Hispanic women, and their associations with Hispanic nativity, and explored whether neighborhood socioeconomic status (SES) and residence in a Hispanic enclave modify the association of nativity with stage and survival. METHODS: We used California Cancer Registry data (1994-2009) to identify 7958 Hispanic women aged 21 years and older with invasive cervical cancer. We used logistic and Cox proportional hazards models to estimate the associations between stage and mortality with nativity, neighborhood factors, and other covariates. RESULTS: Foreign-born women had similar adjusted relative odds of being diagnosed with stages II through IV (vs stage I) cervical cancer compared with US-born Hispanic women. However, among foreign-born women, those in low-SES-low-enclave neighborhoods were more likely to have late-stage disease than those in high-SES-low-enclave neighborhoods (adjusted odds ratio=1.91; 95% confidence interval=1.18, 3.07). Foreign-born women had lower cervical cancer mortality (adjusted hazard ratio=0.67; 95% confidence interval=0.58, 0.76) than US-born women, but only in high enclaves. CONCLUSIONS: Among Hispanic women, nativity, neighborhood enclaves, and SES interact in their influence on stage and survival of cervical cancer.