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Camptothecin (CPT), an alkaloid isolated from the Camptotheca tree, has demonstrated significant anticancer properties in a range of malignancies. However, its therapeutic efficacy is limited by its hydrophobicity, poor bioavailability, and systemic toxicity. Derivatives, analogues, and nanoformulations of CPT have been synthesized to overcome these limitations. The aim of this review is to comprehensively analyze existing studies to evaluate the therapeutic efficacy, mechanistic aspects, and clinical potential of CPT and its modified forms, including derivatives, analogues, and nanoformulations, in cancer treatment. A comprehensive literature review was performed using PubMed/Medline, Scopus, and Web of Science databases; articles were selected based on specific inclusion criteria, and data were extracted on the pharmacological profile, clinical studies, and therapeutic efficacy of CPT and its different forms. Current evidence suggests that derivatives and analogues of CPT have improved water solubility, bioavailability, and reduced systemic toxicity compared to CPT. Nanoformulations further enhance targeted delivery and reduce off-target effects. Clinical trials indicate promising outcomes with enhanced survival rates and lower side effects. CPT and its modified forms hold significant promise as potent anticancer agents. Ongoing research and clinical trials are essential for establishing their long-term efficacy and safety; the evidence overwhelmingly supports further development and clinical testing of these compounds., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Since 2019, Lumpy skin disease (LSD) has suddenly spread in many Asian countries, including India. LSD primarily occurs in cattle. However, recent LSD outbreaks in India have also revealed significant morbidity and production losses in buffaloes. This has raised concerns about the role of buffaloes in the epidemiology and transmission of LSD and necessitates the inclusion of buffaloes in the mass vaccination program for the prevention and control of the disease in the country. However, there is no significant data on the immune response in buffaloes following vaccination with the LSD vaccine. In this study, we evaluated antibody- and cell-mediated immune responses following vaccination with a newly developed live-attenuated LSD vaccine (Lumpi-ProVac Ind ). The detectable amount of anti-LSDV antibodies was observed at 1-2 months following vaccination, with a peak antibody titer at 3 months. Upon stimulation of the peripheral blood mononuclear cells (PBMCs) with the UV-inactivated LSDV antigen, there was a significant increase in CD8 + T cell counts in vaccinated animals as compared to the unvaccinated animals. Besides, vaccinated animals also showed a significant increase in IFN-γ levels upon antigenic stimulation of their PBMCs with LSDV antigen. In conclusion, the buffaloes also mount a potent antibody- and cell-mediated immune response following vaccination with Lumpi-ProVac Ind ., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Ship-breaking yards are recognized for releasing hazardous polycyclic aromatic hydrocarbons (PAHs), leading to severe environmental pollution in the sediment of ship-breaking areas. This study assessed the concentrations of 16 priority PAHs in surface sediments collected from the intertidal zone adjacent to the Sitakund ship-breaking yards. The samples underwent Soxhlet extraction and detection using PerkinElmer GC-Clarus 690 and MS-Clarus SQ8C with an Elite-5MS capillary column (30 m × 0.25 mm ID × 0.25 µm). The study utilized PAH concentrations to reveal spatial distribution patterns, identify point sources, and assess potential toxicity. The total PAH concentration ranged from 1899.2 to 156,800.08 ng g -1 dw, while the concentration of 7 carcinogenic PAHs ranged from 822.03 to 1899.15 ng g -1 dw. High molecular weight PAHs dominated among the 16 PAHs, whereas low molecular weight PAHs, such as 2-ring PAHs, were negligible. Source characterization based on different molecular ratios suggested that PAHs in the area originated from pyrolytic processes related to ship dismantling, fishing activities, and water transportation for people. The observed PAH concentrations exceeded both national and international standards for sedimentary PAH levels, indicating significant ecological risks. The total TEQcarc values of sediment samples varied from 564.41 to 10,695.12 ng g -1 , with a mean value of 3091.25 ng g -1 . The study's findings underscore the immediate biological damage that PAH contamination in the Sitakund ship-breaking area could cause, emphasizing the need for effective control measures to ensure ecological and human safety., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The inhibition of p38 mitogen-activated protein kinase (p38-MAPK) by small molecule chemical inhibitors was previously shown to impair severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, however, mechanisms underlying antiviral activity remains unexplored. In this study, reduced growth of SARS-CoV-2 in p38- α knockout Vero cells, together with enhanced viral yield in cells transfected with construct expressing p38 α , suggested that p38-MAPK is essential for the propagation of SARS-CoV-2. The SARS-CoV-2 was also shown to induce phosphorylation (activation) of p38, at time when transcription/translational activities are considered to be at the peak levels. Further, we demonstrated that p38 supports viral RNA/protein synthesis without affecting viral attachment, entry, and budding in the target cells. In conclusion, we provide mechanistic insights on the regulation of SARS-CoV-2 replication by p38 MAPK., Competing Interests: Conflict of interestThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s), under exclusive licence to Indian Virological Society 2024.)

The success of a species in future climate change scenarios depends on its morphological, physiological, and demographic adaptive responses to changing climate. The existence of threatened species against climate adversaries is constrained due to their small population size, narrow genetic base, and narrow niche breadth. We examined if ecological niche model (ENM)-based distribution predictions of species align with their morpho-physiological and demographic responses to future climate change scenarios. We studied three threatened Ilex species, viz., Ilex khasiana Purkay., I. venulosa Hook. f., and I. embelioides Hook. F, with restricted distribution in Indo-Burma biodiversity hotspot. Demographic analysis of the natural populations of each species in Meghalaya, India revealed an upright pyramid suggesting a stable population under the present climate scenario. I. khasiana was confined to higher elevations only while I. venulosa and I. embelioides had wider altitudinal distribution ranges. The bio-climatic niche of I. khasiana was narrow, while the other two species had relatively broader niches. The ENM-predicted potential distribution areas under the current (2022) and future (2050) climatic scenarios (General Circulation Models (GCMs): IPSL-CM5A-LR and NIMR-HADGEM2-AO) revealed that the distribution of highly suitable areas for the most climate-sensitive I. khasiana got drastically reduced. In I. venulosa and I. embelioides, there was an increase in highly suitable areas under the future scenarios. The eco-physiological studies showed marked variation among the species, sites, and treatments (p < 0.05), indicating the differential responses of the three species to varied climate scenarios, but followed a similar trend in species performance aligning with the model predictions., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Avian influenza viruses (AIV) increase commercial and backyard poultry mortality and morbidity, reduces egg production, and elevates public health risk. Household ducks propagate and transmit HPAI and LPAI viruses between domesticated and wild birds in Southeast Asian countries, including Bangladesh. This study was conducted to identify epidemiological factors associated with AIV infection among household ducks at Chattogram, Bangladesh. We randomly selected and collected blood and oropharyngeal swab samples from 281 households ducks. We evaluated the serum for AIV antibody using cELISA and tested for H5 and H9 subtypes using the HI test. We tested the swabs with real-time reverse transcriptase PCR (rRT-PCR) for M gene, and H5, H9 subtypes. In the duck populations, the household level AIV sero-prevalence was 57.7% (95% CI: 51.6-63.3) and RNA prevalence was 2.4% (95% CI: 1.0-5.0). H5 and H9 subtype sero-prevalence was 31.5% (95% CI: 22.2-42.0) and 23.9% (95% CI: 15.6-33.9). H5 and H9 subtype RNA prevalence were 0% (95% CI: 0.0-1.3) and 2.4% (95% CI: 1.0-5.0). We determined household-level OR (Odds Ratios) for the "combined (mixed materials-mud and concrete or metallic)" category was 2.2 (95% CI: 1.1-4.2) compared with "wooden/bamboo" category (p = 0.02); 2.8 (95% CI: 1.2-6.6) in households with duck plague vaccine coverage compared with no coverage (p = 0.01); and 2.4 (95% CI: 0.6-9.7) in households that threw dead birds in bushes and the roadside compared with households that buried or threw dead birds in garbage pits (p = 0.21). M gene phylogenetic analysis compared M gene sequences to previously reported Bangladeshi H9N2 isolates. The evidence presented here shows AIV circulation in the Chattogram, Bangladesh study areas. AIV reduction can be achieved through farmer education of proper farm management practices., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

This two-dimensional study makes significant incursions into the health-environment literature by interrogating whether non-renewable energy moderates the impact of environmental degradation on mortality rates. It further aligns with the 2030 United Nations Sustainable Development Goals and 11, which aim to ensure healthy lives and promote well-being for all at all ages and make cities and human settlements inclusive, safe, resilient and sustainable. It contributes to the health-environment literature by investigating the intrinsic relationships among mortality rates, carbon emissions (environmental degradation), and non-renewable energy consumption. The study uses an unbalanced sample of 42 Asia and Pacific countries to determine (1) whether carbon emissions exaggerate the incidence of mortality rates and (2) if the interaction of non-renewable energy with carbon emissions enhances or alters the impact of carbon emissions on mortality rates. Consistent findings from the panel spatial correlation consistent least-squares dummy variables (PSCC-LSDV) and two-step system generalized method of moments (GMM) techniques reveal that (i) carbon emissions exacerbate mortality rates; (ii) non-renewable energy consumption exhibit mortality-reducing properties; (iii) non-renewable energy attenuates the impact of carbon emissions on mortality rates, (iv) persistency in mortalities occurs; and (v) the health-environment-energy dynamics differ across income groups. The paper's conjecture is expected to channel a new line of discourse on how non-renewable energy influences the environment and health outcomes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The persistent dwindling of the biocapacity has caused the ecological footprint (EF) to keep increasing in the top ten tourist destinations over the last three decades. Moreso, economic growth, natural resource rent, and urbanization substantially increased for the same period. Tourism contributes to economic prosperity. However, growth in tourism promotes an increase in energy consumption, natural resource exploration, transportation, and consequential ecological distortions. It is important to understand the predictors of EF to suggest suitable policies for environmental sustainability. Hence, this study examines the predictors of EF by considering factors that could influence EF. More precisely, the study analyzes the linkage among economic growth, natural resource rent, urbanization, energy intensity, and tourism using some of the most advanced and reliable econometric techniques, such as Westerlund's (J Appl Econ 23(2):193-233, 2008) cointegration technique, and the continuously updated full modified (CUP-FM) and continuously updated bias-corrected (CUP-BC), long-run estimators. The outcomes of the analysis indicate that EF has a negative association with urbanization and natural resources, which implies that an abundance of natural resources and increasing urban population can help to reduce environmental degradation. Likewise, energy intensity helps in decreasing EF, while economic growth adds to EF. Tourist arrival and tourist receipt also add to EF and, therefore, negatively affect environmental quality. Finally, policy directions are discussed to reduce environmental degradation without reducing economic growth., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Prednisolone dosing regimen based on body surface area (BSA) or body weight (BW) in managing uncomplicated nephrotic syndrome (NS) has been a matter of controversy., Methods: In this parallel-arm randomized clinical trial, 60 children with uncomplicated NS in relapse were randomized to receive either of two regimens. Children of BW cohort received prednisolone (2 mg/kg/day) till remission (or 6 weeks for first episode); followed by 1.5 mg/kg on alternate days for 4 weeks (or 6 weeks for first episode). Children randomized for BSA cohort received prednisolone (60 mg/m 2 /day) till remission (or 6 week for first episode); followed by 40 mg/m 2 on alternate days for 4 weeks (or 6 weeks for first episode). The primary endpoint was 6-month relapse-free survival in the intention-to-treat population (clinical trial registry of India CTRI/2015/03/005655)., Results: The 6-month relapse-free survival rates were similar for both BSA cohort 73.33% (22/30) and BW cohort 70% (21/30) (p = 1, OR 0.19, 95% CI 0.07-0.52). Requirement of cumulative steroid to achieve initial remission (96.1 ± 57.8 vs 63.58 ± 40.2 mg/kg, p = 0.014) and over 6-month study period (104.34 ± 50.82 vs 73.88 ± 42.95 mg/kg, p = 0.015) were significantly higher in BSA cohort in comparison to BW cohort. However, time taken in achieving remission during enrolment episode in both BSA and BW groups was comparable (7 ± 1.7 vs 6.9 ± 1.4 days, p = 0.81). While both treatments were well tolerated, the number of adverse events was one and half times as common in the BSA group than BW group (37 vs. 22 events)., Conclusions: In treating children with uncomplicated NS, both BSA and BW regimens were equally effective in achieving initial remission and maintaining disease remission. Due to fewer adverse events and lesser cumulative steroid exposure with BW based regimen, it may be considered as better option over BSA regimen., Clinical Trial Registry Name: Clinical Trial Registry of India (CTRI/2015/03/005655).

Chicken astroviruses (CAstVs) infect young chicks and are associated with gastroenteritis, stunted growth or visceral gout (gout). True incidence and distribution of CAstVs as well as virus variants circulating in India is not well understood. In this study, 80 gout-affected broiler chicken flocks from Haryana, a north-western state of India, were tested for the presence of astroviruses by targeting the polymerase gene of both CAstV and avian nephritis virus (ANV) and capsid gene of CAstV. Of these, 22 (27.5%) flocks were found positive for CAstV, 7(8.75%) for ANV and 2 (2.5%) for both CAstV and ANV genome by reverse-transcription-polymerase chain reaction. CAstV was isolated by inoculating tissue (kidney) homogenate from gout-affected birds into specific-pathogen free embryonated chicken eggs where the infected embryos showed stunted growth with necrosis of liver and enlarged kidney with urate deposits. Capsid gene-based phylogenetic analysis revealed the clustering of CAstV strains from this study with Indian strains of serogroup Biii suggesting their antigenic relatedness. Thus the present study reveals the presence of chicken astroviruses in broiler chickens affected with gout., Competing Interests: Conflict of interestThe authors declare that there is no any conflict of interest., (© Indian Virological Society 2019.)

Background: Although immune-based therapy has proven efficacious for some patients with microsatellite instability (MSI) colon cancers, a majority of patients receive limited benefit. Conversely, select patients with microsatellite stable (MSS) tumors respond to checkpoint blockade, necessitating novel ways to study the immune tumor microenvironment (TME). We used phenotypic and spatial data from infiltrating immune and tumor cells to model cellular mixing to predict disease specific outcomes in patients with colorectal liver metastases., Methods: Formalin fixed paraffin embedded metastatic colon cancer tissue from 195 patients were subjected to multiplex immunohistochemistry (mfIHC). After phenotyping, the G-function was calculated for each patient and cell type. Data was correlated with clinical outcomes and survival., Results: High tumor cell to cytotoxic T lymphocyte (TC-CTL) mixing was associated with both a pro-inflammatory and immunosuppressive TME characterized by increased CTL infiltration and PD-L1 + expression, respectively. Presence and engagement of antigen presenting cells (APC) and helper T cells (Th) were associated with greater TC-CTL mixing and improved 5-year disease specific survival compared to patients with a low degree of mixing (42% vs. 16%, p = 0.0275). Comparison of measured mixing to a calculated theoretical random mixing revealed that PD-L1 expression on APCs resulted in an environment where CTLs were non-randomly less associated with TCs, highlighting their biologic significance., Conclusion: Evaluation of immune interactions within the TME of metastatic colon cancer using mfIHC in combination with mathematical modeling characterized cellular mixing of TCs and CTLs, providing a novel strategy to better predict clinical outcomes while identifying potential candidates for immune based therapies.

Ship breaking and recycling industry (SBRI) loops back scarce ferrous and non-ferrous materials from dismantled ships and also renews the global shipping fleet by treating the end-of-life (EoL) ships. Currently, SBRIs in Bangladesh, India, and Pakistan are dismantling the majority of the EoL ships by open beaching method. Accordingly, ship dismantling carries the blame of releasing potentially toxic elements (PTEs) to the coastal and marine environment risking the food chain through potential bioaccumulation and biomagnification. Health risk assessment associated with PTEs from open beach ship dismantling is scarce. This study aimed at assessing concentrations and seasonal variations of PTEs in soils exposed to the activities of SBRIs for their source apportionment by using contamination factor (CF) and multivariate statistical analysis, while carcinogenic and non-carcinogenic health risks due to the PTEs have also been determined. Soil samples were collected twice-during pre-monsoon and post-monsoon seasons-from three working zones of each of the 15 different ship breaking yards spanning the entire SBRI zone in Bangladesh. Soil contamination was assessed by using the CF, and inverse distance weighting interpolation mapping showed the spatial distribution of metals at SBRI zone in Bangladesh. Multivariate statistical analysis, principal component analysis, and correlation matrix yielded the source apportionment of PTEs. Subsequently, carcinogenic and non-carcinogenic health risks were assessed following the approach recommended by the United States Environmental Protection Agency (USEPA) with uncertainty estimation through Monte Carlo simulation. Contamination levels of PTEs followed Cd > Zn > Cr > Cu > Pb > Ni > Mn > As. Concentrations of Cd, Cr, Mn, and Zn were higher than the maximum allowable regulatory limits at storage zone and also higher as compared with the beaching and cutting zones in general. The contamination index indicated extreme Cd contamination in the area with elevated levels in pre-monsoon. Two principal components (PC) were identified-PC1 (Cd, Cu, Mn, Pb, Zn) and PC2 (As, Cr, Ni) inferring their source segmentation. Indirect soil ingestion is the major possible exposure path to PTEs. The health index indicated the absence of any obvious health effects on the people active at SBRI yards in Bangladesh. The carcinogenic risk was for 6 to 7 persons per 100,000 people which was within the USEPA acceptable range.

End-of-life (EOL) ships contribute significantly to the flow of recycled industrial Fe and non-Fe metal materials in resource-poor developing countries. The ship scrapping (breaking) and recycling industry (SBRI) recycles 90-95% of the total weight of EOL ships and is currently concentrated in Bangladesh, India, Pakistan, Turkey, and China, due to the high demand for recyclable and reusable materials there, an abundance of low-cost labor, and lenient environmental regulations. However, the SBRI has long been criticized for non-compliance with standards relating to occupational health, labor safety, and to the management of hazardous materials. Among the different EOL recycling options, Bangladesh, India, and Pakistan use open beaching, a technique that exposes all spheres of the environment to the release of hazardous materials from EOL ships. This article summarizes the current state of knowledge on the environmental exposure of hazardous materials from SBRI, to judge the risks associated with the dismantling of EOL ships on open beaches. Our work includes an overview of the industry and its recent growth, compares available ship-breaking methods, provides an inventory of hazardous releases from EOL ships, and reviews their movement into different spheres of the environment. The economic dynamics behind open beaching, and apportionment of responsibility for hazards related to it, are discussed, in order to generate policy and legal recommendations to mitigate the environmental harm stemming from this industry.

Camelpox virus (CMLV), a close variant of variola virus (VARV) infects camels worldwide. The zoonotic infections reported from India signify the need to study the host-range genes-responsible for host tropism. We report sequence and phylogenetic analysis of five host-range genes: cytokine response modifier B (crmB), chemokine binding protein (ckbp), viral schlafen-like (v-slfn), myxomavirus T4-like (M-T4-like) and b5r of CMLVs isolated from outbreaks in India. Comparative analysis revealed that these genes are conserved among CMLVs and shared 94.5-100 % identity at both nucleotide (nt) and amino acid (aa) levels. All genes showed identity (59.3-98.4 %) with cowpox virus (CPXV) while three genes-crmB, ckbp and b5r showed similarity (92-96.5 %) with VARVs at both nt and aa levels. Interestingly, three consecutive serine residue insertions were observed in CKBP protein of CMLV-Delhi09 isolate which was similar to CPXV-BR and VACVs, besides five point mutations (K53Q, N67I, F84S, A127T and E182G) were also similar to zoonotic OPXVs. Further, few inconsistent point mutation(s) were also observed in other gene(s) among Indian CMLVs. These indicate that different strains of CMLVs are circulating in India and these mutations could play an important role in adaptation of CMLVs in humans. The phylogeny revealed clustering of all CMLVs together except CMLV-Delhi09 which grouped separately due to the presence of specific point mutations. However, the topology of the concatenated phylogeny showed close evolutionary relationship of CMLV with VARV and TATV followed by CPXV-RatGer09/1 from Germany. The availability of this genetic information will be useful in unveiling new strategies to control emerging zoonotic poxvirus infections.

Purpose: The aim of this study is to determine whether exposure to hazardous chemicals alters chemokine or cytokine production in macrophages and link these events to changes in intracellular signaling pathways and activation of specific gene promoters., Methods: RAW 264.7 mouse macrophages were treated with selected toxic industrial chemicals (TICs) and examined for changes in immune function. Luminex multiplex technology was used to assess changes in cytokine/chemokine expression and activation of kinase signaling pathways. In addition, a panel of macrophage cell lines with promoter-specific luciferase reporter genes were generated and treated with the TICs, and transcriptional responses to these chemicals were detected by changes in luminescence., Results: Changes in expression of cytokines and chemokines were linked to changes in the activation state of intracellular signaling pathways. Overall, the findings reveal that sublytic levels of TICs can alter the profile of cytokines and chemokines expressed by macrophages, with a pattern that suggests immunosuppression. The data demonstrate that critical changes in immune function correlate with activation of kinase signaling pathways in macrophages., Conclusions: These data provide insight into the effects of sublytic doses of selected TICs on macrophage function, with a particular emphasis on identifying changes in expression of cytokines and chemokines. These altered patterns in immune function were linked to changes in the activation state of intracellular signaling pathways. The data strongly suggest that small amounts of TICs can have subtle, yet very critical, effects on macrophages.

The objective of the study was to observe the effect of protein density of concentrate mixture on the growth performance of Red Chittagong Cattle (RCC) heifers (Bos indicus), an endangered variety in Bangladesh. The experiment was conducted for a period of 90 days with 12 RCC heifers, and the animals were divided into four groups on the basis of their initial live weight. The animals were assigned at random to four dietary treatments having three replications in each in a randomized complete block design. Three iso-energetic [10.5 MJ metabolizable energy (ME)/kg dry matter (DM)] concentrate mixtures were formulated to provide protein concentrations (%) of 15, 20, and 25 for T(1), T(2), and T(3), respectively. Crude protein (CP) content of control diet was 7.08%. Animals of all groups were fed urea molasses straw (UMS) ad libitum and green grass at a rate of 20% of total DM intake. Digestibility of DM was highest in the treatment group fed 25% CP supplement (T(3)) and lowest in the unsupplemented group (T(0)). Average daily gain increased with increasing CP concentration in supplements, but mean difference was not significant between the 20% and 25% CP groups. Feed cost per kilogram live weight gain was lowest (P > 0.05) in 20% CP supplement and highest in the unsupplemented group. The results revealed that the CP concentration of 20% in concentrate mixture containing 10.5 MJ ME is cost effective with the UMS-based diet of RCC heifers for better nutrient digestibility and growth.