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Breast cancer (BC) is the 2nd most common cause of cancer-related deaths. Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to cytotoxic agents and are directed towards a specific tumor protein. Therefore, they are more potent and can have relatively less toxicity. In this meta-analysis, we assessed the efficacy and safety of ADCs in breast cancer. We searched PubMed, Cochrane, Web of Science, and clinicaltrials.gov for relevant studies and included 7 randomized clinical trials (N = 5,302) and 7 non-randomized clinical trials (N = 658). R programming language software was used to conduct this meta-analysis. In 4 RCTs on HER-2 positive BC (N = 2,825), the pooled HR of PFS and OS was 0.72 (95% CI = 0.61–0.84, I2 = 71%) and 0.73 (95% CI = 0.64–0.84, I2 = 20%), respectively in favor of ADCs versus chemotherapy. In RCT on triple negative BC (N = 468), HR of PFS and OS were 0.55 (95%CI = 0.51–0.61) and 0.59 (95% CI = 0.54–0.66), respectively, in favor of saci-gov versus chemotherapy. In RCT on HER-2 positive residual invasive BC, HR of recurrence/death was 0.61 (95% CI = 0.54–0.69) in favor of ADC versus chemotherapy. In an RCT (N = 524), the HR of PFS and OS were 0.28 (95% CI = 0.22–0.37) and 0.55 (95%CI = 0.36–0.86), respectively, in favor of trastuzumab-deruxtecan (T-der) as compared to trastuzumab-emtansine (T-DM1). Anemia, rash, diarrhea, fatigue, hypertension, thrombocytopenia, and elevated aminotransferases were the common ≥grade 3 adverse events reported in 4%, 1%, 2%, 1%, 2%, 9%, and 3% of the patients, respectively. ADCs were more effective than single and double agent chemotherapy in patients with HER-2 positive or triple negative BC. Among ADCs, T-der was more effective than T-DM1.

Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton’s tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Methods: Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, “tyrosine kinase” and “idiopathic thrombocytopenic purpura”. PRISMA guidelines were followed. Results: In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Conclusions: Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP.

The growth and productivity of wheat crops depend on the availability of essential nutrients such as zinc (Zn) and potassium (K2O), which play critical roles in the plant’s physiological and biochemical processes. This study aimed to investigate the synergizing effect of zinc and potassium fertilizers on uptake of both the nutrients, growth, yield, and quality of the Hashim-08 cultivar and local landrace, during the 2019–2020 growing season in Dera Ismail Khan, Pakistan. The experiment was designed using a split plot pattern in a randomized complete pattern, with main plots for the wheat cultivars and subplots for the fertilizer treatments. Results indicated that both cultivars responded positively to the fertilizer treatments, with the local landrace exhibiting maximum plant height and biological yield, and improved Hashim-08, showing increased agronomic parameters, including the number of tillers and grains and spike length. Application of Zn and K2O fertilizers significantly enhanced agronomic parameters, such as the number of grains per plant, spike length, thousand-grain weight, grain yield, harvest index, Zn uptake of grain, dry gluten content, and grain moisture content, while crude protein and grain potassium remained relatively unchanged. The soil’s Zn and K content dynamics were found to vary among treatments. In conclusion, the combined application of Zn and K2O fertilizers proved beneficial in improving the growth, yield, and quality of wheat crops, with the local landrace exhibiting lower grain yield but greater Zn uptake through fertilizer application. The study’s findings highlight that the local landrace showed good response to the growth and qualitative parameter when compared with the Hashim-08 cultivar. Additionally, the combined application of Zn and K showed a positive relation in terms of nutrient uptake and soil Zn and K content.

In the current study, five different plants, Syzygium Cumini, Fagonia cretica, Acacia modesta, Withania coagulans, and Olea europaea aqueous extracts were prepared and applied against the anticancer and antibacterial activities. It was observed that O. Europaea extract shows the highest anticancer activity with cell viability of 21.5%. All the five plants extract was also used against the inhibition of Bacillus subtilis where O. Europaea extract shows a promising inhibitory activity of 3.2 cm followed by W. coagulans. Furthermore, W. coagulans was subjected to the process of column chromatography as a result a withanolide was isolated. The fast atom bombardment mass spectrometry (FAB-MS) and high resolution fast atom bombardment (HRFAB-MS) [M + 1] indicated molecular weight at m/z 453 and molecular formula C28H37O5. The UV–Vis. spectrum shows absorbance at 210 nm suggesting the presence of conjugated system, and Fourier-transform infrared spectroscopy (FTIR) was recorded to explore the functional groups. Similarly, 1D and 2D NMR spectroscopy techniques such as 1H, 13C NMR, correlation spectroscopy (COSY-45°), heteronuclear single quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC) and Nuclear Overhauser effect Spectroscopy (NOESY) techniques was carried out to determine the unknown natural product. The collective data of all these techniques established the structure of the unknown compound and recognized as a withanolide.

Silybummarianum has been used for a variety of purposes all over the world. This plant is used to treat cancer, liver disease, and inflammation. Eleven endophytic bacteria were isolated from S.marianum collected from heavy metal polluted sites and identified using 16s rRNA sequencing in the current investigation. Three isolates stood out for having many features, including heavy metal resistance, plant growth stimulation, plant hormones, heavy metal toxicity remediation, and antibacterial action. SJLC (6.06 µg/L) and SJRB (5.98 µg/L) were the greatest producers of IAA among the isolates and were identified as Bacillus sp. and Lysinibacillus sp., respectively. Root and shoot length have improved as a result of IAA production. The SJLC was found to be effective against four of the pathogens tested. The strain SJLC showed the most activity against Bacillus cereus with a 20 mm zone of inhibition, followed by the isolate SJRB, which showed a 16 mm zone of inhibition against B. cereus. The same isolates also show inhibition against X. campestris. Almost majority of the Brassicanapus plants inoculated with bacterial isolates were able to translocate and degrade heavy metals like Cr. Therefore, it was concluded that these isolates are capable to grow in highly polluted environments.

In this research work, a green synthesis method of using a Nigella sativa L. seeds extract as a reductant was adopted for the silver nanoparticles (AgNP) production. The AgNP were produced using a 5 mM silver nitrate mixed with the seeds extract at 25 °C and at 60 °C. It was observed that the AgNP production rate significantly increased at high temperatures. The obtained AgNP were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) techniques. SEM depicted an average particle size (42 ± 15 nm) of synthesized AgNP. XRD results further augmented the SEM data and indicated definite crystallinic peaks for synthesized AgNP. The prepared Nigella sativa L. extract assisted AgNP (N.S./AgNP) were further used in the reduction of the MB and 4-nitroaniline dyes as well as in antibacterial studies. It was found that the AgNP successfully transformed the 4-NA and MB to their reductive compounds with high conversion rates of 0.1021 min−1 and 0.4197 min−1, respectively. The antibacterial results showed that the N.S./AgNP have good killing properties against Staphylococcus aureus, Klebsiella pneumonia and Pseudomonas aeruginosa bacteria.

In this research work, we present a synthesis of silver and cobalt bimetal nanoparticles stabilized by a carboxymethyl cellulose biopolymer (CMC-AgCo) and its coating on a cellulose filter paper (CFP) to prepare the dip-catalyst. All the prepared samples were subjected to characterization by scanning electron microscopy for surface morphology, EDX, XRD and thermogravimetric analysis. The catalytic properties of the CFP/CMC-AgCo as dip-catalysts were evaluated in the reduction of organic nitroaromatic pollutants of 2,6-dinitrophenol to 2,6-diaminophenol as well as the 4-nitrophenol to 4-aminophenol. It was found that the reduction reaction advanced with the pseudo-first-order kinetics. The CFP/CMC-AgCo catalyzed the 2,6-diaminophenol and 4-nitrophenol with a reaction rate constant of 0.1244 and 0.177 min− 1, respectively. The separation of the CFP/CMC-AgCo was easy as it required a simple pulling of the strip from the reaction medium. Importantly, the catalytic reaction rates and conversion percentages of the two nitroaromatics were well-maintained for multiple times during recycling experiments.

Background B-cell tumors and plasma cell malignancies have been identified in persons living with the human immunodeficiency virus (PLHIV). The literature review has revealed numerous reports of solitary plasmacytomas with metastasis in PLHIV. Case report A young patient with no prior medical or surgical history presented with tumor lysis syndrome secondary to metastatic plasma cell Epstein-Baer virus (EBV) related malignancy with peritoneal carcinomatosis. The history and clinical picture promptly led to the diagnosis of HIV. The subsequent hospital course was dismal, and lifespan was cut short by multi-organ failure. Conclusion This case is being reported to highlight the suspicion of HIV in patients presenting acutely with aggressive plasma cell malignancies.

Probiotics are delivered orally for treating gastrointestinal tract (GIT) infections; thus, they should be protected from the harsh environment of the GIT, such as through microencapsulation. Here, we microencapsulated cells of the probiotic

The synthesis of Vigna radiata (VR) infused CuAg NPs (CuAg/VR), is discussed here for various applications. The CuAg/VR nanoparticles was synthesized by treating the VR impregnated Cu(II) and Ag(I) with NaBH4 in aqueous medium. The CuAg/VR was characterized through FESEM, EDS, XRD, FTIR and TGA analysis. The catalyst was applied for the reduction/degradation of eight model pollutants i.e. nitrophenol isomers 2/3/4 nitrophenols (2/3/4NP), 2,4-dinitrophenol (2,4-dnip), Congo red dye (CR), methyl orange (MO), methylene Blue (MB), and rhodhamine B (RB). The highest rate constant kapp based on pseudo-1st order kinetics was recorded for 4-nirophenol (4NP) among the others which is 2.8 $$\times$$ 10–1 min−1 with turn over frequency (TOF) of 0.056 h−1 for 4NP. The order of nitrophenols reactivity is 2NP $$>$$ 3NP $$>$$ 4NP which are explained on the basis of inductive effect. Among all the nitrophenols and dyes the highest kapp was recorded for RB which is 8.1 $$\times$$ 10–1 min−1. Similarly, simultaneous removal of MB and RB dyes indicated 98% removal of MB and 9% removal of RB dye which shows the selective discoloration of MB dye. At 75 ng/mL the zone of inhibition of CuAg/VR against Methicillin-resistant Staphylococcus aureus (MRSA), was found 26 mm.

The incidence and prevalence of neuroendocrine neoplasms (NENs) has increased in the US in recent decades. These are well-vascularized tumors, but no antiangiogenic drug has been approved for treatment of extra-pancreatic NENs. The aim is to assess efficacy and safety of surufatinib in pancreatic and extra-pancreatic NETs. We searched PubMed, Embase, Cochrane Library, Web of Science and Clinicaltrials.gov. Clinical trials and observational studies that provided safety and efficacy data in clinical terms were included. Characteristics of the study, baseline characteristics of participants, treatment drugs, measures of efficacy, and toxicity (≥grade 3 adverse effects) were extracted. The meta-analysis was performed using the "R" programming language. Risk ratio (RR) of objective response (OR)/partial response (PR) was 8.55 (95% CI: 1.68-43.66, I

Fevipiprant is a non-steroidal oral prostaglandin D2 (PGD2) receptor 2 antagonist that reduces bronchial wall inflammation, possibly improving clinical outcomes in the asthmatic population. A systemic review search was conducted on PubMed, Embase, and Central Cochrane Registry. Randomized clinical trials were included with Fevipiprant as an intervention arm compared to placebo. For continuous variables, the standardized mean difference, and for discrete variables, Mantel-Haenszel Risk Ratio (MH Risk ratio) was used for analysis. Confidence interval of 95% and p-value0.05 was considered significant. The analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. A total of five articles, including seven trials, were included in the analysis. There was significant increase in post-bronchodilator forced expiratory volume in one second (FEV1) 0.249 (0.157-0.341), p0.001 and pre-bronchodilator FEV1 0.115 (0.043 to 0.188), p=0.002. A decrease in asthma control questionnaire (ACQ) score of -0.124 (-0.187 to -0.062), p0.001, was reported. Statistically significant asthma exacerbation reduction was reported in the high eosinophil count population with a daily dose of 450mg 0.77 relative risks (RR) (0.61-0.97). There was a positive deviation toward Fevipiprant 450mg dose for asthma reduction in the overall population, but it was not statistically significant. Fevipiprant produced a slight statistically significant reduction in asthma exacerbations in the high eosinophil count population with favorable deviation in the overall population. It significantly increased pre-and post-bronchodilator FEV1 and improved ACQ scores in treated patients. The benefits, though statistically significant, failed to translate into clinical importance.

CAR T cell therapy is an innovative approach to treat cancers in the modern era. It utilizes the application of chimeric antigen receptors targeted against specific antigens expressed by the tumor cells. Although its efficacy is established in hematological malignancies, the safety and efficacy of this therapy in solid tumors, especially pancreaticobiliary cancers, is a highly investigated aspect. A focused review of clinical data was conducted to examine the outcomes of this therapy in pancreaticobiliary cancers. A comprehensive literature search was done on Medline and Embase databases through April 24, 2020 for studies that evaluated the outcomes of CAR T cell therapy in pancreaticobiliary cancers. There were six phase 1 trials, while one was phase 1/2. Some of these trials were specifically done for pancreaticobiliary cancers, while others included patients of various solid organ cancers, including pancreatic and biliary tract cancers. The target antigens for therapy in these trials included mesothelin, CD133, prostate stem cell antigen, claudin 18.2, epidermal growth factor receptor, and human epidermal growth factor receptor 2. CAR T cell therapy has shown very few grade 3 and 4 side effects. Most of the adverse events are associated with cytokine release syndrome. CAR T cell therapy has a manageable safety profile based on phase 1 studies, and efficacy assessments are currently ongoing in dose expansion and phase 2 studies.

This study was focused to synthesize silver nanoparticles (AgNps) from the aqueous extract of Bistorta amplexicaule and to evaluate their antimicrobial, antifungal, and 4-nitrophenol (4-NP) degradation potential. The AgNps from B. amplexicaule were characterized by field emission scanning electron microscopy, energy dispersive X-ray spectrometry, X-ray diffraction, and X-ray photoelectron spectroscopy studies. The biological activity of the AgNps was checked against the three bacterial and two fungal strains. The inhibition activities of the synthesized nanoparticles on pathogenic bacteria and fungi were equally studied using the colony-forming unit method. The AgNps synthesized showed excellent bactericidal and fungicidal activities against pathogenic Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Candida albicans, and Candida tropicalis. The removal of nitrophenols is one of the most demanding tasks, due to their injurious impact on the health of the living organisms. The AgNps showed superior performance compared with the pure plant extract. The AgNps also displayed efficient catalytic ability in reducing toxic 4-NP into harmless 4-aminophenol in the presence of NaBH4 solution. Hence, the synthesized AgNps can be effectively used against bacterial and fungal infections and in the decontamination of 4-NP polluted water.

Photorhabdus spp. has a high molecular weight Tc toxin with insecticidal activity. These toxins have been suggested as an alternative to BT toxin from Bacillus thuringiensis. Herein, we constructed a cosmid library with the genome of M1021 and screened the Escherichia coli clones showing insect toxicity by injecting each clone into Galleria mellonella larvae. In a total of 1020 clones, one clone with high insecticidal activity was selected and the nucleotide sequence of the cosmid of the clone was determined. In cosmid PtC28, a gene with 87% homology to the tccB gene of Photorhabdus temperata was found. Consequently, we have isolated the tccB gene cassette from the M1021 and expressed in E. coli expression vectors. The toxin was produced in the form of inclusion bodies but the denatured and refolded recombinant TccB showed strong mortality to the G. mellonella larvae.

Background Multiple patients with prostate cancer become resistant to castration therapies, which is termed castration-resistant prostate cancer (CRPC). Purpose The purpose of this review is to assess the status of efficacy (≥50% decline in prostate-specific antigen (PSA), progression-free survival (PFS), and overall survival (OS)) and safety (grade 3-4 adverse effects) of monoclonal antibodies in CRPC. Data source We searched databases including PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov. Results Hazard ratios of PFS and OS were 0.77 (95% CI = 0.69-0.87, I

MnO2 and MnO2 blended with 1 and 2 weight percent of activated carbon (AC), MnO2/AC1 and MnO2/AC2 were synthesized through the sol–gel method. The pure chitosan (CS) films were cast in the form of films. Similarly, 5 weight% of each MnO2, AC, MnO2/AC1 and MnO2/AC2 was intermingled with the CS to produce different films, such as CS-AC, CS-MnO2, CS-MnO2/AC1 and CS-MnO2/AC2. Zero-valent Co NPs were then supported on these films through the chemical reduction method and expressed as CS@Co, CS-AC@Co, CS-MnO2@Co, CS-MnO2/AC1@Co and CS-MnO2/AC2@Co NPs. All the catalysts were characterized by field emission scanning electron microscopy (FESEM), energy-dispersive spectroscopy (EDS) and X-ray diffraction (XRD) techniques. The synthesized catalysts were used as a dip catalyst against the hydrogenation of 4-nitrophenol (4NP), and for the degradation of methyl orange (MO) and Congo red (CR) dyes. The kapp and R2 values were deduced from pseudo-first-order kinetics for 4NP and MO and zero-order kinetics for CR dye. The kapp values of CS-AC@Co and CS-MnO2/AC1@Co NPs for 4NP hydrogenation were higher than those for any other member of the series, at 1.14 × 10−1 and 1.56 × 10−1 min−1 respectively. Similarly, the rate of CR degradation was highest with CS-AC@Co. The R2 values for 4NP, MO and CR dyes were above 0.9, which indicated that the application of pseudo-first- and zero-order models were appropriate for this study. Furthermore, the antibacterial activity of all the catalysts was evaluated against Pseudomonas aeruginosa and Escherichia coli. The CS-AC@Co NPs exhibited the highest zone of inhibition compared to other catalysts against P. aeruginosa, while all the catalysts were inactive against E. coli. This study reveals that the catalyst can be used for the degradation of other pollutants and for microbial inhibition.

Water pollution reached worrying point due to different dye pollutants which demands an instant solution. One of the best ways to manage water pollutants is their reduction and decolorization to less-toxic and useful compounds. However, reduction process requires an effective, stable, and recyclable catalyst to reduce such pollutants more effectively. Metal nanoparticles (M

MnO

The development of a solid substrate for the support and stabilization of zero-valent metal nanoparticles (NPs) is the heart of the catalyst system. In the current embodiment, we have prepared solid support comprise of alginate-coated cellulose filter paper (Alg/FP) for the synthesis and stabilization of Co nanoparticles (NPs) named as Alg/FP@Co NPs. Furthermore, Alginate polymer was blended with 1 and 2 weight percent of CoNi NPs to make Alg-CoNi1/FP and Alg-CoNi2/FP, respectively. All these stabilizing matrixes were used as dip-catalyst for the degradation of azo dyes and reduction of 4-nitrophenol (4NP). The effect of initial dye concentration, amount of NaBH4, and catalyst dosage was assessed for the degradation of Congo red (CR) dye by using Alg-CoNi2/FP@Co NPs. Results indicated that the highest kapp value (3.63 × 10−1 min−1) was exhibited by Alg-CoNi2/FP@Co NPs and lowest by Alg/FP@Co NPs against the discoloration of CR dye. Furthermore, it was concluded that Alg-CoNi2/FP@Co NPs exhibited strong catalyst activity against CR, and methyl orange dye (MO) degradation as well as 4NP reduction. Antibacterial activity of the prepared composites was also investigated and the highest l activity was shown by Alg-CoNi2/FP@Co NPs, which inhibit 2.5 cm zone of bacteria compared to other catalysts.

Camellia sinensis L. has long been used as a therapeutic agent for the Central nervous system (CNS) due to the presence of flavonoids. The present study aimed to evaluate the dose-dependent Neuropharmacological behavioral potential of Camellia sinensis seed and leaf extracts on mice. To evaluate the differential potential of leaf and seed extract various doses were prepared and examined in open field, head dip, rearing, cage cross, swimming and traction tests. One-way ANOVA set at P*